BICYCLIC NITROGEN COMPOUNDS AS MODULATORS OF GHRELIN RECEPTOR AND USES THEREOF

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application Nos. 60/755,714, entitled "INDOLE COMPOUNDS AS MODULATORS OF GHRELIN RECEPTOR AND USES THEREOF", filed December 30, 2005; and 60/835,241 , entitled "INDOLE COMPOUNDS AS MODULATORS OF GHRELIN RECEPTOR AND USES THEREOF, filed August 2, 2006, both of which are incorporated by reference in their entireties.

BACKGROUND OF THE INVENTION Field of the Invention ^'

[0002] This invention relates to the fields of organic chemistry, pharmaceutical chemistry, biochemistry, molecular biology and medicine. In particular it relates to compounds that modulate the activity of the human Growth Hormone Secretagogue receptor (GHSRIa, Ghrelin receptor), and to the use of the compounds for the treatment and prevention of disorders or conditions such as obesity, eating disorders, hormone insufficiencies, dwarfism; somatopause, osteoporosis, wasting syndromes, catabolic states, cardiovascular diseases, gastrointestinal diseases, sleep disorders, cancers; for disorders of the pancreas, diabetes, anxiety disorders and cognitive deficits, and for diagnosing hormone insufficiencies.

Description of the Related Art

[0003] The physiological actions of the hormone/neurotransmitter ghrelin are mediated, in part, by the ghrelin receptor. The ghrelin receptor is expressed in a number of tissues including the pituitary and hypothalamus, as well as other brain regions such as hippocampus, as well as peripheral tissues such as heart, lung, pancreas, stomach, intestine, and adipose tissue and numerous other tissues where it is thought to regulate appetite, energy balance, cardiovascular function, gastrointestinal motility, hormone release, induction of slow wave sleep, and cellular proliferation (Inui A, et al. FASEB J. 2004 Mar;18(3):439-56.

Deghenghi R. et al. Endocrine. 2003 Oct; 22(1): 13-8. Bona G et al. Panminerva Med. 2003 Sep;45(3): 197-201. Broglio F. et al. Horm Res. 2003;59(3):109-17).

[0004] Compounds that stimulate ghrelin receptors have been shown to stimulate appetite and food intake, improve cardiac output and reduce cardiac afterload, stimulate gastric motility and emptying, facilitate induction of sleep, and inhibit cellular proliferation in cells derived from the lung, thyroid and breast. Compounds that block ghrelin receptor activity have been shown to facilitate weight loss, reduce appetite, reduce food intake, facilitate weight maintenance, treat obesity, treat diabetes and associated side effects, (including retinopathy and/or cardiovascular disorders), and reduce metabolism. (Inui A, et al. FASEB J. 2004 Mar;18(3):439-56. Deghenghi R. et al. Endocrine. 2003 Oct; 22(1): 13-8. Bona G et al. Panminerva Med. 2003 Sep;45(3): 197-201. Broglio F. et al. Horm Res. 2003 ;59(3): 109-17).

SUMMARY OF THE INVENTION [0005] One embodiment disclosed herein relates to a compound of Formula (I):

(I) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, wherein:

A can be selected from the group consisting of hydrogen, halogen, cyano, mono- substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, -C(=Z)R,, -C(=Z)OR,, -C(=Z)NR _Ia R _{I b} , -C(R,)=NR _la , -NR _la R _lb , -N=CR _{l a} R, _b , -N(R,)-C(=Z)R,, -N(R,)-C(=Z)NR _la R _lb , -S(O)NR, _a R, _b , -S(O) ₂ NR _{1 a} R _lb , -N(R,)-S(=O)R,, -N(Ri)-S(=O) ₂ Ri, -ORi, -SRi, and -OC(=O)R,;

B can be selected from the group consisting of hydrogen; mono-substituted, poly- substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl,

cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, -C(=Z)R,, -C(=Z)OR,, -C(=Z)NR _{l a} Ri _b , -C(=Z)N(OR _la )R, _b> -C(=Z)N(R,)NR _{l a} R _lb5 -C(RO=NR ₁₃ , -G≡N; -NR _la Ri _b , -N=CR _la R _lb , -N(R,)-C(=Z)R _h -N(R,)-C(=Z)NR _la R _{l b} , -S(O)NR _Ia R _lb , -S(O) ₂ NR _{1 a} R _{l b} , -N(R,)-S(=O)R,, -N(RO-SC=O) ₂ R ₁ , - S(O)Ri, -S(O) ₂ R ₅ , -OR,, -SR ₁ , and -OC(O)Ri; or

A and B can be taken together to form an unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heteroalicyclyl;

Ri ₁ Ri _a and Ri _b can each independently selected from the group consisting of hydrogen, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl and haloalkyl;

R ₂ and Ra _a can each independently selected from the group consisting of hydrogen, cyano, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, -C(=Z)R,, -C(=Z)ORi, -C(=Z)NR _la R _lb , -C(R,)=NR _la , -(C _1-4 alkyl)-Z-aryl, -(C _M alkyl)C(=O) R ₁ , -NR, _a R _)b , -N=CR _la R _lb , -N(R,)-C(=Z)R], -N(R,)-C(=Z)NR _la R _lb> -S(O)NR _la R _lb , - S(O) ₂ NRi ₃ R _n ,, or

R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl;

R ₃ , R ₃₃ , R _3bj and R _3c can each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, -C(=Z)R,, -C(=Z)0R,, -C(=Z)NR, _a R _lb , -C(RO=NR ₁₃ , -NR _la R _lb , - N=CR _{l a} R _lb , -N(R,)-C(=Z)Ri, -N(R,)-C(=Z)NR, _a R _{l b} , -S(O)NR, _a R, _b , -S(O) ₂ NR _Ia R _{l b} , -N(R,)-S(=O)R _{l 3} -N(R0-S(=O) ₂ R,, -ORi , -SR ₁ , and -OC(=Z)R,;

R- _3> R _3a» R _θb , and R ₃ C can be taken together with one or more adjacent members of the group consisting of R ₃ , R _3a , R _3b, and R _3c to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

R. _3C can be taken together with B to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

L can be an unsubstitυted or substituted lower alkylene group, wherein when L is substituted, it is substituted with one .or more group(s) individually and independently selected from the group consisting of alkyl, alkenyl, halogen, haloalkyl, alkoxy, haloalkoxy, hydroxyl, and -CN;

L can be taken together with R ₃ to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

Y can be C-R ₃ or N; and

Z can be O or S.

[0006] Another embodiment disclosed herein relates to a pharmaceutical composition, comprising a therapeutically effective amount of a compound of Formula (I) and/or a compound described herein, and a pharmaceutically acceptable carrier, excipient, or diluent.

[0007] Still another embodiment disclosed herein relates to a method of treating or preventing a disorder or condition comprising administering to a subject a pharmaceutically effective amount of a compound of Formula (I) and/or a compound described herein. In some embodiment, the compound of Formula (I) and/or one of the compound described herein alleviates or treats a disorder or condition by modulating, agonizing, inverse agonizing, or antagonizing a ghrelin receptor.

BRIEF DESCRIPTION OF THE DRAWINGS [0008] Figure 1 is a graph showing the inverse agonists activities of compounds at ghrelin receptors in R-SAT assays.

[0009] Figure 2 is a graph showing the inverse agonist and agonist activities of compounds at ghrelin receptors in phosphatidyl inositol assays

[0010] Figure 3 is a graph sho222wing the spontaneous feeding activity in freely moving, fasted, male Sprague-Dawley rats following intraperitoneal administration of ghrelin receptor antagonists/inverse agonists.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT [0011] Small molecules with heretofore-unappreciated activities have been identified as ghrelin receptor antagonists/inverse agonists. We further demonstrate that these compounds suppress feeding in rats. These observations have practical applications that support the use of these compounds to alleviate or treat disorders or conditions affected directly or indirectly through ghrelin receptors.

[0012] A large number of compounds of Formula I were screened for functional activity at the Ghrelin receptor and display robust ghrelin receptor antagonist/inverse agonist activity.

[0013] One embodiment disclosed herein relates to a compound of Formula (I):

(1) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, wherein: _/

A can be selected from the group consisting of hydrogen, halogen, cyano, mono- substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfϊnyl, sulfonyl, haloalkyl, haloalkoxy, -NR _{i a} R _lb , -N=CR _Ia R _lb , -N(R,)-CC=Z)R _{l 5} -NCR,)-CC=Z)NR _la R _lb , -SCO)NR _la R _lb , -SCO) ₂ NR _la R _lb , -NCRi)-SC=O)R ₁ , -NCRi)-SC=O) ₂ R ₁ , -OR ₁ , -SR ₁ , and -OCC=O)R ₁ ;

B can be selected from the group consisting of hydrogen; mono-substituted, poly- substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, Cheteroalicyclyl)alkyl, -CC=Z)R ₁ , -C(=Z)OR,, -CC=Z)NR _!a R _lb , -CC=Z)N(ORi _a )R _{l b} , -CC=Z)NCR ₁ )NR ₁₃ R _{1 b} , -C(Ri)=NR ₁₃ , -C=N; -NR _la R _lb , -N=CR _{I a} R _lb , -N(R,)-C(=Z)R,, -N(R,)-C(=Z)NR _{l a} R _lb , -S(O)NR _la Rib _s -S(O) ₂ NR _Ia R _Ib , -N(R,)-S(=O)R,, -N(RO-SC=O) ₂ R ₁ , - SCO)R ₁ , -SCO) ₂ R,, -ORi, -SRi, and -OC(=O)Ri; or

A and B can be taken together to form an unsubstituted or substituted cycloalkyl, or unsubstituted or substituted heteroalicyclyl;

Ri, Ri _a and R^ can each independently selected from the group consisting of hydrogen, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl and haloalkyl;

R ₂ and R _2a can each independently selected from the group consisting of hydrogen, cyano, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, -C(=Z)R,, -C(=Z)OR,, -CC=Z)NRi _a Rib, -C(R,)=NR _Ia , -(C _M alkyl>Z-aryl, -(C _M alkyl)C(=O) R ₁ , -NR _la R _lb , -N=CR _la R _{l b} , -NCRO-CC=Z)R ₁ , -N(R,)-C(=Z)NR _lβ R, _b , -S(O)NR _{l a} R _Ib , - SCO) ₂ NRi _a R _Ib , -N(RO-SC=O)R ₁ , -NCRO-SC=O) ₂ R ₁ , -OR ₁ , -SR ₁ , and -OCC=Z)R ₁ ; or

R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl;

R _3J R ₃ a, R ₃₁₅ , and R _3C can each independently selected from the group consisting of hydrogen, halogen, cyano, nitro, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, Cheteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, -NR, _a Ri _b , - N=CR _la R _{l b} , -N(RO-CC=Z)R ₁ , -N(R,)-C(=Z)NR _{l a} Rib, -SCO)NR _la R _lb , -S(O) ₂ NR, _a R _Ib , -N(RO-SC=O)R ₁ , -OR ₁ , -SR ₁ , and -OCC=Z)R ₁ ;

R3, R ₃ a, R ₃ b, and R _3c can be taken together with one or more adjacent members of the group consisting of R ₃ , R ₃₃ , R3b, and R ₃₀ to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

R ₃₀ can be taken together with B to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

L can be an unsubstituted or substituted lower alkylene group, wherein when L is substituted, it is substituted with one or more group(s) individually and independently

selected from the group consisting of alkyl, alkenyl, halogen, haloalkyl, alkoxy, haloalkoxy, hydroxyl, and -CN;

L can be taken together with R ₃ to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring;

Y can be C-R ₃ or N; and

Z can be O or S.

[0014] In some embodiments, the compound of Formula (I) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, has the structure described herein provided that when R ₂ and R ₂₈ are taken together, along with the nitrogen atom to which they are attached, form a substituted heteroalicyclyl, wherein the

substituted heteroalicyclyl i i .ss ^ ^~-^^ i substituted with n-butyl at the para-position, then B cannot be selected from the group consisting of methyl, -C(=O)Ri, and -CH ₂ OH, wherein Ri is hydrogen or methyl; or A cannot be methyl. In other embodiments, the compound of Formula (I) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, has the structure described herein provided that when R ₂ and R _2a are taken together, along with the nitrogen atom to which they are attached, form a substituted

heteroalicyclyl, wherein the substituted heteroalicyclyl i .s ^^ substituted with an alkyl, such as n-butyl, then A, R ₃ , R _3a , R _3b, and R ₃₀ cannot all be hydrogen.

[0015] Another embodiment disclosed herein relates to a compound of Formula (I) that modulates, agonizes, inverse agonizes, or antagonizes a ghrelin receptor. In some embodiments, a compound of Formula (I) inverse agonizes or antagonizes a ghrelin receptor. In some embodiments, the compound of Formula (I) binds to a ghrelin receptor with an IC50 value in the range of about 9 to about 5. In certain embodiments, the compound of Formula (I) binds to a ghrelin receptor with an IC ₅ 0 value in the range of about 9 to about 6. In some embodiments, the compound of Formula (I) binds to a ghrelin receptor with an IC ₅₀ value in the range of about 9 to about 7. In certain embodiments, the compound of Formula (I) binds to a ghrelin receptor with an IC ₅₀ value in the range of about 9 to about 8.

[0016] In some embodiments, Y can be C-R ₃ . In other embodiments, Y can be N (nitrogen).

[0017] With respect to R ₂ and R ₂₈ , in some embodiments, R ₂ , and/or R _2a can be hydrogen. In other embodiments, R ₂ , and/or R _2a can be cyano. In still other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted alkyl. In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In some embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted alkynyl. In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted cycloalkyl. In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted cycloalkenyl. In still other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted cycloalkynyl. In still other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly- substituted or unsubstituted aryl. In some embodiments, R ₂ , and/or R _2a can be a mono- substituted, poly-substituted or unsubstituted heteroaryl. In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted heteroalicyclyl. In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted aralkyl. In still other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly- substituted or unsubstituted heteroaralkyl. In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted (heteroalicyclyl)alkyl. In some embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)Rι. In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)ORi. In other embodiments, R ₂ , and/or R _2a can be a mono- substituted, poly-substituted or unsubstituted-C(=Z)NR] _a Rit,. In some embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -C(Ri)=NRi ₃ . In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -NRι _a Rn _> . In still other embodiments, R ₂ , and/or R ₂₃ can be a mono- substituted, poly-substituted or unsubstituted -N=CRi _a Rib. In some embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -(Cι-4alkyl)-Z-aryl. In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted - (Ci- ₄ alkyl)C(— O). In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-

substituted or unsubstituted -N(Ri)-C(=Z)Ri. In some embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -N(R))-C(=Z)NRi _a Ri _b - In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted - S(O)NRi _a Rib- In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly- substituted or unsubstituted -S(O) ₂ NRi _a Rib- In some embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -N(Ri)-S(=O)Ri. In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -N(Rι)-S(=O) ₂ Rι _. In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -ORi. In yet other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted -SR _\ . In some embodiments, R ₂ , and/or R _2a can be a mono- substituted, poly-substituted or unsubstituted -OC(=O)Ri. In some embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted sulfinyl. In other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted sulfonyl. In yet other embodiments, R ₂ , and/or R ₂₃ can be a mono-substituted, poly- substituted or unsubstituted haloalkyl. In yet still other embodiments, R ₂ , and/or R _2a can be a mono-substituted, poly-substituted or unsubstituted haloalkoxy.

[0018] In some embodiments, R _2a can be selected from the group consisting mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl. aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, Rj,. In one embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted alkyl. In another embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In still another embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted alkynyl. In yet still another embodiment, R _2a can be a mono-substituted, poly- substituted or unsubstituted cycloalkyl. In one embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted cycloalkenyl. In another embodiment, R _2a can be a mono- substituted, poly-substituted or unsubstituted cycloalkynyl. In still another embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted aryl. In yet still another embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted heteroaryl. (e.g., substituted or unsubsituted pyridine). In one embodiment, R _2a can be a mono-

substituted, poly-substituted or unsubstituted heteroalicyclyl. In another embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted aralkyl (e.g., substituted or unsubstitued phenyl(methyl), substituted or unsubstitued phenyl(ethyl)), substituted or unsubstitued phenyl(propyl)). In still another embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted heteroaralkyl (e.g., substituted or unsubsituted indole). In yet still another embodiment, R _2a can be a mono-substituted, poly-substituted or unsubstituted (heteroalicyclyl)alkyl. In some embodiments, R _2a can be -(Ci- ₄ alkyl)-Z-aryl. In other embodiments, R _2a can be (Ci.4alkyl)C(=O) R|. In any of the embodiments of described in this paragraph, R ₂ can be hydrogen. In any of the embodiments of described in this paragraph, R ₂ can be an alkyl such as methyl.

[0019] In certain embodiments, the cycloalkenyl can be . In some embodiments, Ri and R _2a cannot both be hydrogen. In other embodiments, R ₂ cannot be hydrogen when R _2a is an alkyl. In other embodiments, R ₂ and R ₂₈ cannot both be a lower alkyl. In still other embodiments, R ₂ and R _2a cannot be hydrogen or alkyl when B is — C(=0) NR _Ia R _lb .

[0020] In some embodiments, R ₂ and R2 _a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl. Examples wherein R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl include but are not limited to the following:

[0021 J In certain embodiments, R. ₂ and R _2a can be taken together, along with the

nitrogen atom to which they are attached, to form an unsubstituted or substituted ^~^ . In other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which

N they are attached, to form an unsubstituted or substituted ■O ' . In yet other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to

form an unsubstituted or substituted . In some embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an

unsubstituted or substituted . IImn other embodiments, R2 and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

N substituted F ^\ In yet other embodiments, R ₂ and R ₂₈ can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

. in still other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

. In still other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted ,^λ ^ . In some embodiments, R ₂ and R _2B can be taken together, along with the

nitrogen atom to which they are attached, to form an unsubstituted or .

In other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to

which they are attached, to form an unsubstituted or substituted . In yet other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they

are attached, to form an unsubstituted or substituted . In still other embodiments,

R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to

form an unsubstituted or substituted ^ . In yet other embodiments, R ₂ and R _2a can be

taken together, along with the nitrogen atom to which they are attached, to form an

unsubstituted or . In other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

the nitrogen atom to which they are attached, to form an unsubstituted or

substituted . In other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted , In yet other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they ^' are attached, to form an unsubstituted or

In some embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted . In other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted . In yet other embodiments, R ₂ and R ₂₃ can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted . In still other embodiments, R ₂ and R. _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted _o tø _er embodiments, R ₂ and R. _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

. In some embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

. In other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted ^^ ^{^} ^ . In still other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted | _{n o} ther embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

In yet other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted' — ' . In still other embodiments, R ₂ and R _2a can be taken together, along with

the nitrogen atom to which they are attached, to form an unsubstituted or substituted

In still other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to

which they are attached, to form an unsubstituted or substituted In some embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they

are attached, to form an unsubstituted or . In certain embodiments,

R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to

form an unsubstituted or substituted . In other embodiments, R ₂ and R ₂₃ can be taken together, along with the nitrogen atom to which they are attached, to form an

unsubstituted or substituted . In yet other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an

unsubstituted or substituted . In some embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted . In other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted . In yet other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

. In still other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

. In still other embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted . In some embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or

substituted

[0022] In some embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl selected from the group consisting of:

certain embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which

they are attached, to form an unsubstiluted or substituted

[0023] When R ₂ and R _2a are taken together, along with the nitrogen atom to which they are attached, to form a substituted heteroalicyclyl such as those described herein, the substituted heteroalicyclyl can be substituted with one or more group(s) individually and independently selected from the group consisting of hydrogen, halogen, cyano, nitro,

hydroxyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heteroalicyclyl, (heteroalicyclyl)alkyl, alkoxy, aryloxy, ester, mercapto, alkylthio, arylthio, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N- thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato, isothiocyanato, C-carboxy, O-carboxy, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino.

[0024] In certain embodiments, R ₂ and R _2a are taken together, along with the nitrogen atom to which they are attached, to form a substituted heteroalicyclyl such as those described herein (e.g., paragraphs [0014] and [0015]), wherein the substituted heteroalicyclyl can be substituted with one or more group(s) suitable groups. In some embodiments, the

substituted heteroalicyclyl is substituted w /iitthh ^π ° ⁿ .. IInn certain embodiments,

be n-butyl or n-pentyl. In other embodiments, the substituted heteroalicyclyl

can be substituted with . In yet other embodiments, the substituted heteroalicyclyl

can be substituted with ⁿ . In some embodiments, the substituted heteroalicyclyl

can be substituted with ^HO >λ ⁿ . In other embodiments, the substituted heteroalicyclyl can

be substituted with ^HS >r ^{x n} . In yet other embodiments, the substituted heteroalicyclyl can

be substituted with . I _n still other embodiments, the substituted

heteroalicyclyl can be substituted with . In still other embodiments, the

substituted heteroalicyclyl can be substituted with . . In some embodiments,

the substituted heteroalicyclyl can be substituted w /iitthh ^w ^w ; V ^ _. . _l I _n n. other embodiments,

the substituted heteroalicyclyl can be substituted with ^v . In yet other embodiments,

the substituted heteroalicyclyl can be substituted with ^R "b ^R 4 ^a N ? _{In sti} jj _other

embodiments, the substituted heteroalicyclyl can be substituted with yet

other embodiments, the substituted heteroalicyclyl can be substituted w ith . In

other embodiments, the substituted heteroalicyclyl can be substituted wi

certain embodiments, the substituted heteroalicyclyl can be substituted with

In other embodiments, the substituted heteroalicyclyl can be substituted with

. In yet other embodiments, the substituted heteroalicyclyl can be

substituted with . In some embodiments, the substituted heteroalicyclyl

can be substituted with . In other embodiments, the substituted

heteroalicyclyl can be substituted with In yet other embodiments,

the substituted heteroalicyclyl can be substituted with In still other

embodiments, the substituted heteroalicyclyl can be substituted with

In still other embodiments, the substituted heteroalicyclyl can be substituted with

In some embodiments, the substituted heteroalicyclyl can be

substituted with In other embodiments, the substituted

heteroalicyclyl can be substituted with . In still other embodiments,

the substituted heteroalicyclyl can be substituted with . In other embodiments, the substituted heteroalicyclyl can be substituted with

. In yet other embodiments, the substituted heteroalicyclyl can be

substituted with . In still other embodiments, the substituted

heteroalicyclyl can be substituted with . In still other embodiments,

the substituted heteroalicyclyl can be substituted with . In some embodiments, the substituted heteroalicyclyl can be substituted with

. In other embodiments, the substituted heteroalicyclyl can be

substituted with In some embodiments, the substituted

heteroalicyclyl can be substituted with . In other embodiments, the

substituted heteroalicyclyl can be substituted with . In still other

embodiments, the substituted heteroalicyclyl can be substituted with

In other embodiments, the substituted heteroalicyclyl can be substituted . In yet other embodiments, the substituted heteroalicyclyl can be substituted with

In still other embodiments, the substituted heteroalicyclyl can be

substituted with In still other embodiments, the substituted

heteroalicyclyl can be substituted with . In some embodiments, the

substituted heteroalicyclyl can be substituted with . In other

embodiments, the substituted heteroalicyclyl can be substituted with

In still other embodiments, the substituted heteroalicyclyl can be substituted with

In other embodiments, the substituted heteroalicyclyl can be

substituted with In yet other embodiments, the substituted

heteroalicyclyl can be substituted with In still other embodiments, the

substituted heteroalicyclyl can be subs rttiittuutteedd wwiitthh In still other

embodiments, the substituted heteroalicyclyl can be substituted with . In some embodiments, the substituted heteroalicyclyl can be substituted with

[0025] In certain embodiments, R ₂ and R _2a cannot be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted N- morpholinyl, an unsubstituted or substituted piperidinyl, an unsubstituted or substituted piperiazinyl, an unsubstituted or substituted azetidinyl, or an N-oxide of an amine group when B is -C(=O)Ri, wherein Ri is an unsubstituted or substituted phenyl, an unsubstituted or substituted Cβ-s cycloalkyl, unsubstituted or substituted styryl, unsubstituted or substituted biphenyl, unsubstituted or substituted napthyl, unsubstituted or substituted anthryl, unsubstituted or substituted thienyl, unsubstitited furyl, unsubstituted or substituted quinolyl, or unsubstituted or substituted pyrrolyl. In some embodiments, R ₂ and R _2a cannot be selected from the group consisting of hydrogen, Ci-βalkyl, C ₃ .i ₅ cycloalkyl, C ₃ -isheterocycloalkyl, heteroaryl and aryl. In some embodiments, R ₂ and R _2a cannot be taken together along with the nitrogen atom to which they are attached, to form a heteroaryl.

[0026] In some of the embodiments described herein, n can be 0. In other embodiments described herein, n can be 1. In yet other embodiments described herein, n can be 2. In some embodiments described herein, n can be 3. In other embodiments described herein, n can be 4. In yet other embodiments described herein, n can be 5. In still other embodiments described herein, n can be 6.

[0027] In some of the embodiments described herein, m can be 0. In other embodiments described herein, m can be 1. In yet other embodiments described herein, m can

be 2. In some of the embodiments described herein, m can be 3. In other embodiments described herein, m can be 4. In yet other embodiments described herein, m can be 5. In still other embodiments described herein, m can be 6. Also, included herein are any combination of n and m (e.g., n is 0 and m is 2, n is 3 and m is 1 , n is 2 and m is 0, etc.).

[0028] In some embodiments described herein, Q can be oxygen. In other embodiments described herein Q can be sulfur.

[0029] When R ₂ and R _2a are taken together, along with the nitrogen atom to which they are attached, to form a substituted heteroalicyclyl, the group(s) substituents attached to the substituted heteroalicyclyl can be also be substituted. In some embodiments, any one or more of R _4a , R4 _b , R ₄ C, IW, IW, IW and R _4g can be hydrogen. In other embodiments, any one or more of R _4a , R ₄ ^ R4 _C , R ₄ (I _J IW, IW and R4 _g can be halogen. In yet other embodiments, any one or more of R _4a , can be cyano. In some embodiments, any one or more of R _4a , R^, R4., R _4d ,, R _4e> IW and R4 _g can be nitro. In other embodiments, any one or more of R _4a , R4b, R _4C ϊW, IW, IW and R4g can be hydroxyl. In yet other embodiments, any one or more of R _4a , R4b, R ₄ C ₅ IWi ₃ IW, R4r and R4 _g can be a mono- substituted, poly-substituted or unsubstituted alkyl. In still other embodiments, any one or more of R _4a , R^ can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In still other embodiments, any one or more of R _4a , R4f and R4 _g can be a mono-substituted, poly-substituted or unsubstituted alkynyl. In some embodiments, any one or more of R _4a , R4b, R _4C R _4d ,, R ₄ ^ R-if and R ₄ ^ can be a mono- substituted, poly-substituted or unsubstituted cycloalkyl. In other embodiments, any one or more of R _4a , R-ib, R _4C R _4d ,, R _4C R ₄ P and R4 _g can be a mono-substituted, poly-substituted or unsubstituted cycloalkenyl. In yet other embodiments, any one or more Of R _4a , R ₄ ^ R _4C i IW, R ₄ C R4f and R_4 _g can be a mono-substituted, poly-substituted or unsubstituted cycloalkynyl. In still other embodiments, any one or more of R _4a , R4 _b , R _4C , R^ _d , IW, IW and R _4g can be a mono-substituted, poly-substituted or unsubstituted aryl. In yet other embodiments, any one or more of R _4a , R/jb, R ₄ C, R4_, R _4C IW and R^g can be a mono-substituted, poly-substituted or unsubstituted heteroaryl. In other embodiments, any one or more of R _4a , R ₄ ^ R _4C , IW, IW ₅ R4 _f and R ₄₆ can be a mono-substituted, poly-substituted or unsubstituted aralkyl. In certain embodiments, any one or more of R _4a , R ₄ ^ R _4C , R^d ₅ R _4e , R-Jf and R ₄ ^ can be a mono-

substituted, poly-substituted or unsubstituted heteroaralkyl. In other embodiments, any one or more of R _4a , R ₄ I ₃ , R4 ₀ R _4d ,, R4f and R4 _g can be a mono-substituted, poly-substituted or unsubstituted heteroalicyclyl, In yet other embodiments, any one or more of R _4a , R4b, R _4C , R ₄ Ci, R _4C R4 _f and R4 _g can be a mono-substituted, poly-substituted or unsubstituted (heteroalicyclyl)alkyl. In some embodiments, any one or more of R _4a , R ₄ I,, R ₄ C, R ₄ Ci, R4 ₀ R<ιr and R _4g can be a mono-substituted, poly-substituted or unsubstituted alkoxy. In other embodiments, any one or more of R _4a , R ₄ I,, R4 _C , Rw ₅ R ₄ 0 R-4f and R«jg can be a mono- substituted, poly-substituted or unsubstituted aryloxy. In yet other embodiments, any one or more of R ₄₈ , R-4b ₃ R ₄ C ₃ R-4d, R _4e , R4f and R4 _g can be a mono-substituted, poly-substituted or unsubstituted ester. In certain embodiments, any one or more of R _4a , R ₄ I ₃ , R ₄ C, R _4d ,, R ₄ ^ R4f and R4 _g can be a mono-substituted, poly-substituted or unsubstituted mercapto. In other embodiments, any one or more of R _4a , R ₄ b, R4c, R ₄ Ci, R _4e , R4f and R4 _g can be a mono- substituted, poly-substituted or unsubstituted alkylthio, In yet other embodiments, any one or more of R _4a , R4b, R ₄ C, R ₄ Ci, R _4e , R4f and R_4 _g can be a mono-substituted, poly-substituted or unsubstituted ary lthio. In some embodiments, any one or more of R _4a , R4b, R ₄ C, R ₄ (I, R ₄ ^ R4f and R^g can be a mono-substituted, poly-substituted or unsubstituted carbonyl. In other embodiments, any one or more of R _4a = R4b, R4c, R ₄ Ci, R _4e , R4f and R4 _g can be a mono- substituted, poly-substituted or unsubstituted thiocarbonyl. In yet other embodiments, any one or more Of R _4a , R4b, R _4C R ₄ Ci ₃ R _4e , R4f and R4 _g can be a mono-substituted, poly-substituted or unsubstituted O-carbamyl. In some embodiments, any one or more of R _4a , R ₄ I ₅ , R4c, R _4d ,, R _4e , R _4f and can be a mono-substituted, poly-substjtuted or unsubstituted N-carbamyl. In other embodiments, any one or more of R _4a , R-ib, R ₄ C, R _4d ,, R _4e , R4f and R4 _g can be a mono- substituted, poly-substituted or unsubstituted O-thiocarbamyl, In yet other embodiments, any one or more Of R _4a , R ₄ ^ R ₄ C, R _4d ,, R4e ₃ R4f and R ₄ ^ can be a mono-substituted, poly-substituted or unsubstituted N-thiocarbamyl. In some embodiments, any one or more of R _4a , R4 _b , R ₄ C ₃ R ₄ Ci ₃ R ₄ C R4f and R^ can be a mono-substituted, poly-substituted or unsubstituted C-amido. In other embodiments, any one or more of R _4a , R4b ₃ R ₄ H, R-td, R _4e , R4f and R^ can be a mono- substituted, poly-substituted or unsubstituted N-amido. In yet other embodiments, any one or more of R _4a , R4b, R _4C , R-i _d , R4 _e , R4f and R _4a can be a mono-substituted, poly-substituted or unsubstituted S-sulfonamido. In certain embodiments, any one or more of R _4a , R ₄ ^ R _4C , R _4d ,

R _4e , R4 _f and R ₄₈ can be a mono-substituted, poly-substituted or unsubstituted N-carbamyl. In other embodiments, any one or more of R _4a , R^b ₅ R ₄ C ₃ ϊ^id, R _4e3 IW and R4 _g can be a mono- substituted, poly-substituted or unsubstituted N-sulfonamido, In yet other embodiments, any one or more of R _4a , R ₄ ^ R _4C ^Ud, R _4e> R^ and R4 _g can be a mono-substituted, poly-substituted or unsubstituted isocyanato. In some embodiments, any one or more of R _4a , R415, R4c, R _4d ,, R _4C , R _4f and R _4g can be a mono-substituted, poly-substituted or unsubstituted thiocyanato. In other embodiments any one or more of R _4a , R41,, R _4C R _4d ,» R _4e . FUf and R4 _g can be a mono- substituted, poly-substituted or unsubstituted isothiocyanato. In yet other embodiments, any one or more of R4 ₈ , R ₄ ^ R _JCJ R4 _d> R4 ₀ IW and R^g can be a mono-substituted, poly-substituted or unsubstituted C-carboxy. In certain embodiments, any one or more of R _4a , R^ ₅ R _4C5 R ₄ d _> R _4e , R4f and R4 _g can be a mono-substituted, poly-substituted or unsubstituted O-carboxy. In other embodiments, any one or more of R _4a , R4b, R4c, R-4d _> R _4C R4f and R4g can be a mono- substituted, poly-substituted or unsubstituted silyl, In yet other embodiments, any one or more of R _4a , R ₄ b, R-tc, R _4d ,, R _4e , R4f and R ₄₆ can be a mono-substituted, poly-substituted or unsubstituted sulfenyl, In some embodiments, any one or more Of R _4a , R4b, R ₄ C, R _4d ,, R<te, R4f and R4g can be a mono-substituted, poly-substituted or unsubstituted sulfmyl. In other embodiments, any one or more of R _4a , R4b ₅ R _4C R _4d , _> R _4e , R4f and Rxi _g can be a mono- substituted, poly-substituted or unsubstituted sulfonyl. In yet other embodiments, any one or more of R _4a , R ₄ ^ R ₄ C, R _4d ,, R4 _e j &4f and R^g can be a mono-substituted, poly-substituted or unsubstituted haloalkyl. In certain embodiments, any one or more of R _4a , R^, R _4C , R _4d ,, R _AC , R _4T and R_ _4g can be a mono-substituted, poly-substituted or unsubstituted haloalkoxy. In other embodiments, any one or more of R _4a , R _4b R _4C R _4d ,, R^e, R4f and R ₄₆ can be a mono- substituted, poly-substituted or unsubstituted trihalomethanesulfonyl, In yet other embodiments, any one or more of R _4a , R ₄ ^ R ₄ ^ IW R _4C R4f and R ₄₆ can be a mono- substituted, poly-substituted or unsubstituted trihalomethanesulfonamido. In some embodiments, any one or more of R _4a , R-ib, R _4C R-4d ₅ R^e ₅ R4f and R _4a can be a mono- substituted, poly-substituted or unsubstituted amino. Also, include herein are any combination of any one or more of R _4a , R ₄ ^ R _4C , R ₄ d _> R _4e> R4f and R^g as described in this paragraph (e.g., R _4H is H and R ₄ ( _J is halogen, R _4J is alkyl and R _4b is haloalkyl, etc.).

[0030] In certain embodiments, R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl, which is unsubstituted or substituted with one or more group(s) individually and independently selected from the group consisting of:

[0031] In some embodiments, any one or more of R^ R-t _a , R4b, R4c R _4d ,, R _4e , R4f and R _4g can each independently be selected from the group consisting of hydrogen, halogen, cyano, nitro, hydroxyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkoxy, aryl, alkylthio (e.g., H ₃ CS-), and haloalkyl. In one embodiment, at least one of R _4a , R ₄ ^ R ₄ C, R _4d ,, R _4e , Rf and/or R _g can be halogen. In another embodiment, more than one OfR _4a , R ₄ I,, R ₄ C, R ₄ Ci ₅ Rαe. Rr and/or R _g can be halogen. In another embodiment, at least one of R _4a , R4b, R _4C Rf and/or R _g can be an alkoxy such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and/or t-butoxy. Preferably, the alkoxy is methoxy. In still another embodiment at least one of R _4a , R4b, R ₄ C, Rid, R _4e , Rf and/or R _g can be an alkyl. Exemplary alky Is include but are not limited to methyl, ethyl, n- propyl, isopropyl, n-butyl, isobutyl, and t-butyl. In preferred embodiments, the alkyl can be methyl and/or ethyl. In yet still another embodiment, at least one OfR _4a , R4 ₁ ,, R ₄ C ₃ R _4d , R _4e , R _f and/or R _g can be an aryl (e.g., pyridine). In one embodiment, at least one of R _4J ,, R _4I ,, R _4C , R _4C i ₅ R/ie, R _f and/or R _g can be a haloalkyl such as CF3.

[0032] As to B, in some embodiments, B can be hydrogen. In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted alkyl. In yet other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted alkenyl.

In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted alkynyl. In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted cycloalkyl. In yet other embodiments, B can be a mono-substituted, poly- substituted or unsubstituted cycloalkenyl. In still other embodiments, B can be a mono- substituted, poly-substituted or unsubstituted cycloalkynyl. In still other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted aryl. In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted heteroaryl. In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted heteroalicyclyl. In yet other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted aralkyl. In still other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted heteroaralkyl. In yet other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted (heteroalicyclyl)alkyl. In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)R|. In some embodiments, B can be a mono- substituted, poly-substituted or unsubstituted -C(=Z)ORi . In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)NR| _a Ri _t ,. In yet other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)N(Ri)NRi _a Riι _> . In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -C(Rι)=NRι _a . In yet other embodiments, B can be a mono- substituted, poly-substituted or unsubstituted -CsN. In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -NRι _a Rib- In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted In yet other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -N(R|)-C(=Z)R|. In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -N(Ri)-C(=Z)NR _)a Rib- In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -S(O)NRi ₃ Ri b- In yet other embodiments, B can be a mono- substituted, poly-substituted or unsubstituted -S(O) ₂ NRi ₈ Ri _b - In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted , -N(R _J )-S(=O)RJ . In other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -N (Ri)-S C=O) ₂ R], In yet other embodiments, B can be a mono -substituted, poly-substituted or

unsυbstituted -S(O)Ri. In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -S(O^Ri- In other embodiments, B can be a mono-substituted, poly- substituted or unsubstituted -OR]. In yet other embodiments, B can be a mono-substituted, poly-substituted or unsubstituted -SRi . In some embodiments, B can be a mono-substituted, poly-substituted or unsubstituted , -OC(=O)R|.

[0033] In some embodiments, any one or more of Ri, Rj _a and Rib can be hydrogen. In other embodiments, any one or more of Ri, Ri ₃ and Ri _b can be a mono- substituted, poly-substituted or unsubstituted alkyl. In certain embodiment, the alkyl can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, linear or branched pentyl, linear or branched hexyl, linear or branched heptyl, and/or linear or branched octyl. Preferably, the alkyl can be methyl, ethyl, n-butyl, isobutyl, linear hexyl, and/or branched octyl. In yet other embodiments, any one or more of Ri, Ri _a and R^ can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In some embodiments, any one or more of R], Ru and Rib can be a mono-substituted, poly-substituted or unsubstituted alkynyl. In other embodiments, any one or more of Ri ₁ Ri _a and Ri _b can be a mono-substituted, poly-substituted or unsubstituted cycloalkyl. In a preferred embodiment, the cycloalkyl is cyclopropyl. In yet other embodiments, any one or more of R^ Ri ₃ and Rib can be a mono- substituted, poly-substituted or unsubstituted cycloalkenyl. In still other embodiments, any one or more of Ri, Ri ₃ and Rib can be a mono-substituted, poly-substituted or unsubstituted cycloalkynyl. In still other embodiments, any one or more of Rj ₁ Ri _a and R^ can be a mono-substituted, poly-substituted or unsubstituted aryl such as phenyl. In some embodiments, any one or more of Ri, Rj ₈ and Rib can be a mono-substituted, poly-substituted or unsubstituted heteroaryl. In other embodiments, any one or more of Ri, R| _a and Rj _b can be a mono-substituted, poly-substituted or unsubstituted heteroalicyclyl. In yet other embodiments, any one or more of R| _, R| _a and Ri _b can be a mono-substituted, poly-substituted or unsubstituted aralkyl. In certain embodiment, the aralkyl is an optionally substituted phenyl(C].4alkyl) such as optionally substituted phenyl(methyl). If substituted, the phenylCC^alkyl) can be substituted with one or more substituents including but not limited to alkyl (e.g., methyl) and/or halogen. In still other embodiments, any one or more of Rj ₁ Ri ₈ and Ri _b can be a mono-substituted, poly- substituted or unsubstituted heteroaralkyl. In yet other embodiments, any one or more of Ri ₁

Ri _a and Ri _b can be a mono-substituted, poly-substituted or unsubstituted (heteroalicyclyl)alkyl. In other embodiments, any one or more of Ri, Ri ₃ and Rib can be a haloalkyl, for example CF ₃ .

[0034] In some embodiments when B is -C(=O)Ri, Ri, can be a mono- substituted, poly-substituted or unsubstituted variant of the following residues: alkyl, alkenyl, cycloalkyl, aryl, aralkyl, and/or haloalkyl. In other embodiments when B is -C(=O)Ri, Ri, can be a mono-substituted, poly-substituted or unsubstituted alkyl. In still other embodiments when B is -C(=O)Ri, Ri, can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In yet still other embodiments when B is — C(=O)Rι, Ri, can be a mono-substituted, poly-substituted or unsubstituted cycloalkyl. In some embodiments when B is — C(=O)R], Rj, can be a mono-substituted, poly-substituted or unsubstituted aryl. In other embodiments when B is Ri, ^" can be a mono-substituted, poly-substituted or unsubstituted aralkyl. In still other embodiments when B is — C(=O)Ri, Ri, can be a mono-substituted, poly-substituted or unsubstituted haloalkyl.

[0035] In some embodiments, when B is — C(=O)NRi _a NRib, Ri _a and/or Rn, can each be a mono-substituted, poly-substituted or unsubstituted variant of the following residues: alkyl, alkenyl, cycloalkyl, aryl, aralkyl, and/or haloalkyl. In other embodiments when B is -C(=O)NRi _a NRib, Ria and/or Rib can each be a mono-substituted, poly-substituted or unsubstituted alkyl. In still other embodiments when B is Rι _a and/or Ri _b can each be a mono-substituted, poly-substituted or unsubstituted alkenyl. In yet still other embodiments when B is — C(=O)NRi _a NRib, Ru and/or Rib can each be a mono- substituted, poly-substituted or unsubstituted cycloalkyl. In some embodiments when B is — C(=O)NRi _a NRi _b , Ri _a and/or R^ can each be a mono-substituted, poly-substituted or unsubstituted aryl. In other embodiments when B is — C(=O)NRi _a NRib, R] ₃ and/or R^ can each be a mono-substituted, poly-substituted or unsubstituted aralkyl. In still other embodiments when B is — C(=O)NRi _a NR)b, Ria and/or R|b can each be a mono-substituted, poly-substituted or unsubstituted haloalkyl.

[0036] In some embodiments, when B is — C(=O)ORi, Ri, can be a mono- substituted, poly-substituted or unsubstituted variant of the following residues: alkyl, alkenyl, cycloalkyl, aryl, aralkyl, and/or haloalkyl. In other embodiments when B is — C(=O)OR), R|,

can be a mono-substituted, poly-substituted or unsubstituted alkyl. In still other embodiments when B is — C(=O)ORι, Ri, can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In yet still other embodiments when B is -C(=0)OR|, Ri ₅ can be a mono-substituted, poly-substituted or unsubstituted cycloalkyl. In some embodiments when B is — C(=O)OR|, Ri, can be a mono-substituted, poly-substituted or unsubstituted aryl. In other embodiments when B is Ri ₅ can be a mono-substituted, poly-substituted or unsubstituted aralkyl. In still other embodiments when B is -CC-O)ORi, Rj, can be a mono-substituted, poly-substituted or unsubstituted haloalkyl.

[0037] In some embodiments when B is -C(=O)NRi _a NRi _b , or - CC=O)ORi, Ri, Ria and/or Rib can be an alkyl such as methyl, ethyl, n-propyl, isopropyl, n- butyl, isobutyl, t-butyl, linear or branched pentyl, linear or branched hexyl, linear or branched heptyl, and/or linear or branched octyl. Preferably, the alkyl can be methyl, ethyl, n-butyl, isobutyl, linear hexyl, and/or branched octyl. In other embodiments when B is - C(=O)NR[ _a NR|b, or — C(=O)OR|, Ri, Ri _a and/or Rib can be a cycloalkyl such as cyclopropyl. In still other embodiments when B is -C(=O)Ri, -C(=0)NR| _a NRi _b , Or -CC=O)OR ₁ , Ri, Ri ₃ and/or R^ can be an aralkyl. In certain embodiment, the aralkyl is an optionally substituted phenyl(Ci_ ₄ alkyl) such as optionally substituted phenyl(methyl). If substituted, the phenyl(C|. ₄ alkyl) can be substituted with one or more substituents including but not limited to alkyl (e.g., methyl) and/or halogen. In yet still other embodiments when B is — C(=O)R| _, - CC=O)NR ₁ aNRi _b , or -C(=O)ORi, Ri, Rj ₃ and/or Ri _b can be a haloalkyl (e.g., CF ₃ ).

[0038] With respect to R ₃ , R _3a , R3 _b , and R _3c , in some embodiments, any one or more of R ₃ , R ₃₃ , R _3b , and R _3c can be hydrogen. In other embodiments, any one or more of R ₃ , R _3a , R _3b , and R ₃₀ can be halogen. In still other embodiments, any one or more of R ₃ , R ₃₃ , R3 _b , and R _3C can be cyano. . In yet other embodiments, any one or more of R ₃ , R ₃₈ , R _3b , and R _3c can be nitro. In other embodiments, any one or more of R ₃ , R ₃₈ , R3b, and R _3c can be a mono- substituted, poly-substituted or unsubstituted alkyl. In yet other embodiments, any one or more of R ₃ , R _3a , R _3b, and R _3c can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In some embodiments, any one or more of R ₃ , R _3a , R _3b , and R _3c can be a mono- substituted, poly-substituted or unsubstituted alkynyl. In other embodiments, any one or more of R ₃ , R _3a , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted

cycloalkyl. In yet other embodiments, any one or more of R ₃ , R ₃₈ , R ₃ b, and R _3c can be a mono-substituted, poly-substituted or unsubstituted cycloalkenyl. In still other embodiments, any one or more of R ₃ , R ₃₈ , R3t _> , and R _3c can be a mono-substituted, poly-substituted or unsubstituted cycloalkynyl. In still other embodiments, any one or more of R ₃ , R ₃₈ , R _3IJ1 and R _3c can be a mono-substituted, poly-substituted or unsubstituted aryl. In some embodiments, any one or more of R ₃ , R _3a , R ₃ b, and R ₃₀ can be a mono-substituted, poly-substituted or unsubstituted heteroaryl. In other embodiments, any one or more of R ₃ , R _3a , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted heteroalicyclyl. In yet other embodiments, any one or more of R ₃ , R _3a , R ₃ b, and R _3c can be a mono-substituted, poly- substituted or unsubstituted aralkyl. In still other embodiments, any one or more of R ₃ , R _3a , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted heteroaralkyl. In yet other embodiments, any one or more of R ₃ , R _3a , R ₃ b, and R _3c can be a mono-substituted, poly- substituted or unsubstituted (heteroalicyclyl)alkyl. In other embodiments, any one or more of R ₃ , R ₃₈ , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)Ri . In some embodiments, any one or more of R ₃ , R _3a , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)OR|. In other embodiments, any one or more of R ₃ , R3a, R ₃ b, and R _3c can be a mono-substituted, poly-substituted or unsubstituted-C(=Z)NRi ₈ Rib. In some embodiments, any one or more of R ₃ , R _3a , R ₃ b, and R _3c can be a mono-substituted, poly-substituted or unsubstituted -C(Ri)=NRi ₃ . In other embodiments, any one or more of R ₃ , R ₃₈ , R ₃ b, and R _3c can be a mono-substituted, poly-substituted or unsubstituted-NRi _a Rib- In still other embodiments, any one or more of R ₃ , R _3a , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted -N=CRi _a Rib- In yet other embodiments, any one or more of R ₃ , R ₃₈ , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted -N(Ri)-C(=Z)R|. In some embodiments, any one or more of R ₃ , R ₃₈ , R _3b , and/or R _3c can be a mono-substituted, poly-substituted or unsubstituted -N(Ri)-C(=Z)NRi _a Rib. In other embodiments, any one or more of R ₃ , R ₃₈ , R ₃ b, and R _3c can be a mono-substituted, poly- substituted or unsubstituted -S(O)NRi _a Rib. In yet other embodiments, any one or more of R ₃ , R-38! R3b, and R _3c can be a mono-substituted, poly-substituted or unsubstituted -S(O) ₂ NRi _a Ri _b . In some embodiments, any one or more of R ₃ , R _3a , R _3b , and R _3c can be a mono-substituted, poly-substituted or unsubstituted -N(R|)-S(=O)R]. In other embodiments, any one or more of

R-3, R ₃ a, R-3b, and R _3C can be a mono-substituted, poly-substituted or unsubstituted -N(R|)-S(=O) ₂ R|. In yet other embodiments, any one or more of R3, R _3a , R _3bi and R ₃₀ can be a mono-substituted, poly-substituted or unsubstituted -ORi. In yet other embodiments, any one or more Of R ₃ , R ₃₈ , Rab, and R _3c can be a mono-substituted, poly-substituted or unsubstituted - SRj. In some embodiments, any one or more of R ₃ , R _3a , R _3b , and R ₃₀ can be a mono- substituted, poly-substituted or unsubstituted -OC(=O)Ri . In some embodiments, R _3c can be taken together with B to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring. In other embodiments, R _3c cannot be taken together with B to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring. In some embodiments, any one or more of R ₃ , R _3a , R _3I , _, and R _3c can be a mono-substituted, poly-substituted or unsubstituted sulfinyl. In other embodiments, any one or more of R ₃ , R _3a , R _3b% and R _3c can be a mono-substituted, poly-substituted or unsubstituted sulfonyl. In yet other embodiments, any one or more of R ₃ , Rsa, R3b, and R _3c can be a mono-substituted, poly-substituted or unsubstituted haloalkyl. In yet still other embodiments, any one or more Of R ₃ , R _3a , R _3bj and R _3c can be a mono-substituted, poly-substituted or unsubstituted haloalkoxy. In certain embodiment, any one or more of R ₃ , R3a, R3b, and R _3c can be an alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and t-butyl. Preferably, any one or more of R ₃ , R _3a , R ₃ b, and R ₃ C can be methyl and/or ethyl. In certain embodiment, any one or more Of R ₃ , R _3a , R3b, and R ₃₀ can be -ORi, wherein Ri can be selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and t-butyl. In a preferred embodiment, Rj, can be selected from the group consisting of methyl and isopropyl.

[0039] In some embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of hydrogen, halogen, cyano, nitro, mono-substituted, poly-substituted or unsubstituted variants of the following residues: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, -C(=Z)R|, -C(=Z)OR|, -C(=Z)NR _la R, _b , -C(R,)=NR _Ia , -NR, _a R, _b , -N=CR _{I a} R _{l b} , -N(R,)-C(=Z)R,, -N(R,)-C(=Z)NR _la R _lb , -S(O)NR _la R,b, -S(O) ₂ NR, _a Rib, -N(R,)-S(=O)R,, -N(R,)-S(=O) ₂ R,, - ORi, -SR ₁ , and -OC(=Z)Rj. In certain embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl, alkoxy, -G≡N, and halogen. In some

embodiments, Y can be C-R ₃ , wherein R ₃ can be an alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and t-butyl. In an embodiment, the alkyl can be methyl or ethyl. In some embodiments, Y can be C-R ₃ , wherein R ₃ can be an alkoxy such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, and t-butoxy. In other embodiments when R ₃ is an alkoxy, the alkoxy can be methoxy. In some embodiments, Y can be C-R ₃ , wherein R ₃ can be a -CsN. In some embodiments, Y can be C-R ₃ , wherein R ₃ can be a halogen. In some embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl, alkoxy, -C≡N, and halogen; and B can be -C(=O)Ri. In other embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl, alkoxy, -C≡N, and halogen; and B can be -CC=O)OR],. In still other embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl, alkoxy, -CsN, and halogen; and B can be -C(=Z)NRi _a Ri _b . In yet still other embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl, alkoxy, -CsN, and halogen; and B can be In some embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl, alkoxy, -CsN, and halogen; and B can be -CsN. In some embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl (e.g, methyl), alkoxy (e.g., methoxy), -C≡N, and halogen; B can be and R] can be a mono-substituted, poly-substituted or unsubstituted alkyl such as methyl. In other embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl (e.g, methyl), alkoxy (e.g., methoxy), -C≡N, and halogen; B can be -CO=O)Ri; and Ri can be a mono-substituted, poly-substituted or unsubstituted cycloalkyl such as cyclopropyl. In some embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl (e.g, methyl), alkoxy (e.g., methoxy), -C≡N, and halogen; B can be -C(=O)Ri; and Ri can be a mono-substituted, poly-substituted or unsubstituted aryl (e.g., phenyl). In other embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl (e.g, methyl), alkoxy (e.g., methoxy), -CsN, and halogen; B can be and Ri can be a mono-substituted, poly-substituted or unsubstituted aralkyl such as a phenyl(C|. ₄ alkyl). In other embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl (e.g, methyl), alkoxy (e.g., methoxy), -CsN, and halogen; B can be -C(=O)Rι; and Ri can be a mono-substituted, poly-substituted or unsubstituted haloalkyl (e.g., CF ₃ ). In some

embodiments, Y can be C-R ₃ , wherein R ₃ can be selected from the group consisting of alkyl, alkoxy, -CsN, and halogen; B can be selected from the group consisting of -C( ¹ O)Ri, - C(O)ORi, -C(=Z)NR _{) a} Rib, -C(=Z)N(ORi _a )Ri _b , and -Cs=N; and R ₂ and R _2a can be taken together, along with the nitrogen atom to which they are attached, to form an unsubstituted or substituted heteroalicyclyl such as those described herein.

[0040] As to A, in some embodiments, A can be hydrogen. In other embodiments, A can be halogen. In still other embodiments, A can be cyano. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted alkyl. In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted alkenyl. In some embodiments, A can be a mono-substituted, poly- substituted or unsubstituted alkynyl. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted cycloalkyl. In yet other embodiments, A can be a mono-substituted, poly- substituted or unsubstituted cycloalkenyl. In still other embodiments, A can be a mono- substituted, poly-substituted or unsubstituted cycloalkynyl. In still other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted aryl. In some embodiments, A can be a mono-substituted, poly-substituted or unsubstituted heteroaryl. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted heteroalicyclyl. In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted aralkyl. In still other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted heteroaralkyl. In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted (heteroalicyclyl)alkyl. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)Ri. In some embodiments, A can be a mono- substituted, poly-substituted or unsubstituted -C(=Z)0Ri. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted -C(=Z)NRi _a Rib. In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted - NR _{I 3} R _1I ,. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted -N=CRi _a Ri _b . In yet other embodiments, A can be a mono-substituted, poly- substituted or unsubstituted -N(Ri)-C(=Z)Ri . In some embodiments, A can be a mono- substituted, poly-substituted or unsubstituted In other embodiments,

A can be a monorsubstituted, poly-substituted or unsubstituted -S(O)NR| _a Ri _b - In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted -S(O) ₂ NRi ₈ RIb- In some embodiments, A can be a mono-substituted, poly-substituted or unsubstituted , -N(R|)-S(=O)R]. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted -N(Ri)-S(=O) ₂ R|. In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted -ORi . In yet other embodiments, A can be a mono- substituted, poly-substituted or unsubstituted -SRi . In some embodiments, A can be a mono- substituted, poly-substituted or unsubstituted , -OC(=0)Ri. In some embodiments, A can be a mono-substituted, poly-substituted or unsubstituted sulfinyl. In other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted sulfonyl. In yet other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted haloalkyl.. In yet still other embodiments, A can be a mono-substituted, poly-substituted or unsubstituted haloalkoxy. In a preferred embodiment, A is hydrogen. In another preferred embodiment, A is an alkyl such as methyl.

10041] In certain embodiments, A cannot be an aryl group. In some embodiments, A cannot be a heteroaryl group. In certain embodiments, A cannot be mono-substituted, poly- substituted or unsubtituted -C(=O)NRi _a Rib, wherein Rj ₃ is hydrogen and R^ is heteroaryl or heteroalicyclyl. In certain embodiments, A cannot be mono-substituted, poly-substituted or unsubstituted -C(=O)NRi _a Rib wherein Ri ₃ is hydrogen and R^ is heteroaryl or heteroaliyclyl such as thiazolyl, oxazolyl, isoxazolyl, 1 ,3,4-thiadiazolyl 1,2,4-thiadiazolyl, 1,3,4- oxadiazolyl, 1 ,2,4-oxadiazolyl, pyrazolyl, 1,2,4-triazolyl, tetrazolyl, 3-oxo-pyrazolyl, 3-oxo- imidazolyl, 3- oxo-thiazolyl, thiazolidinyl, pyridyl, pyrimidinyl, pyrazinyl, 1 ,3,5-triazinyl, 1 ,2,4-traizinyl, benyzlimidazolyl, 4-oxo-pyrimidyl, pyridazinyl and 2-oxo-pyrimidyl.

[0042] In certain embodiments when B is wherein Ri ₃ and/or Ri _b are hydrogen, a momo-substituted, poly-substituted or unsubstituted variant selected from the group consisting of alkyl, cycloalkyl, and aryl, R ₂ and/or R _2a cannot be hydrogen, aminoalkyl, or alkylcarbonyl. In some embodiments when B is — C(=O)NRi _a Rib, R ₂ and R _2a cannot be taken together, along with the nitrogen atom to which they are attached, to form a N-morpholinyl group. In some embodiments when B is — C(=O)NR| _a R|b, R ₂ and R _2a cannot be taken together, along with the nitrogen atom to which they are attached, to form an

unsubstituted heteroalicyclyl. In still other embodiments, B cannot be — C(=O)Ri, wherein R| is a cycloalkyl such as a C ₃ . ₈ cycloalkyl. In yet still other embodiments, B cannot be - C(=O)Ri, wherein Rj is a cycloalkyl (e.g, a C ₃ - ₈ cycloalkyl) when R ₂ and R _2a are a mono- or di-substituted aminocarbonylalkyl, a mono- or di-substituted aminosulfonylalkyl, a mono- or di-substituted aminoalkyl. In certain embodiments, B cannot be mono-substituted, poly- substituted or unsubstituted -C(-O)NR| _a Ri _b wherein Ri _a is hydrogen and R|b is heteroaryl or heteroalicyclyl. In certain embodiments, B cannot be mono-substituted, poly-substituted or unsubstituted wherein Ri _a is hydrogen and Rib is heteroaryl or heteroalicyclyl such as thiazolyl, oxazolyl, isoxazolyl, 1,3,4-thiadiazolyl, tetrazolyl, 3-oxo- pyrazolyl, 3-oxo-imidazolyl, 3-oxo-thiazolyl, thiazolidinyl, pyridyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1 ,2,4-triazinyl, benzylimidazolyl, 4-oxo-pyrimidyl, pyridazinyl and 2-oxo- pyrimidyl. In some embodiments, B cannot be -C(=O)Ri, wherein Ri is an unsubstituted or substituted phenyl. In some embodiments, B cannot be — C(=O)R], wherein Rj is an unsubstituted or substituted phenyl, when R ₂ is hydrogen or Ci _-4 alkyl and R _2a is - SO ₂ NRIaRIb, wherein Rj _a and Rib are hydrogen or a In some embodiments, B cannot be — C(=O)NRi _a Rib wherein Ri ₃ is hydrogen and Rib is C3-ioalkyl, Cs-iocarbocycle (e.g, unsubstituted Cs-iocarbocycle or a Cs-iocarbocycle substituted with methyl) when R ₂ is hydrogen and R _2a is or haloalkylsulfonyl such as CF3SO2-. In some embodiments, B cannot be a heteroalicyclyl. In certain embodiments, B cannot be piperdinyl or 1,2,3,6-tetrahydropyridinyi

[0043] In some embodiment, A and B can be taken together to form an unsubstituted or substituted cycloalkyl. In other embodiments, A and B can be taken together to form an unsubstituted or substituted heteroalicyclyl.

[0044] In some of the embodiments, L can be an unsubstituted or substituted lower alkylene group. Preferably, L is ethylene, propylene, or butylene. More preferably, L is propylene. IfL is substituted, suitable substituents without limitation are alkyl (e.g., methyl), alkenyl, halogen, haloalkyl (e.g., CF ₃ ) , alkoxy (e.g, methoxy), haloalkoxy, hydroxyl, and — CN. In some embodiments L cannot a monosubstituted lower alkylene group, wherein the lower alkylene is monosubstituted with a hydroxyl group, when R ₂ and R _2a are both hydrogen or methyl. In certain embodiments, L cannot a monosubstituted lower alkylene group,

wherein the lower alkylene is monosubstituted with a branched alky] group, In some embodiments, L can be taken together with R ₃ to form a cycloalkyl, cycloalkenyl, cycloalkynyl, or heteroalicyclyl ring. In other embodiments, L cannot be taken together with R ₃ to form a cycloalkyl, cycloalkenyl, cycloalkynyl,or heteroalicyclyl ring.

[0045} Some embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of A can be combined with any one or more embodiments of B, Ri, Ri _a , Rib, R ₂ , R ₂₈ , R3, R3a, R _3b , R _3c , L, Y, Z, Q, n, m, R _4a , R4b, R _4C R _4d ,, Rte, R4f, and R ₄₈ .

[0046] Other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of B can be combined with any one or more embodiments of A, Ri, Ria, Rib, R ₂ , R ₂₃ , R ₃ , R ₃ a, R _3b , R _3c , L, Y, Z, Q, n, m, R _4a , R4b, R ₄ C, R _4d ,, R4e, R»f, and R ₄₈ .

[0047] Still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of Ri can be combined with any one or more embodiments of

A, B ₅ R _{) a} , Rib, R ₂ , R _2a , R ₃ , R ₃ a, R ₃ b, R ₃ C, L, Y, Z, Q, n, m, R _4a , R4b, Rtc, R _4d ,> ,R _4e , R45 and

R _4g .

[0048] Yet still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of Rj ₂ can be combined with any one or more embodiments of A ₅ B, Rj, Rn,, R ₂ , R2a, R3, R ₃ a, R ₃ b, R _3c , L, Y, Z, Q, n, m, R _4a , R^b, R4c R _4d ,,

[0049] Some embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of Ri _b can be combined with any one or more embodiments of A,

B, R ₁ , R _la , R ₂ , R _2a , R ₃ , R ₃ a, R _3b , R _3c , L, Y, Z, Q, n, m, R _4a , R ₄ ^ R _4C R _4d ,, Rte, R4f, and R ₄₈ .

(0050] Other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R ₂ can be combined with any one or more embodiments of A, B, Ri, R _!a , R _!b , R _2a , R ₃ , R ₃ a, R ₃ b, R _3c , L, Y, Z, Q, n, m, R _4a , R4b, R4 _C , Rtd, Rie, ^Ur, and R4g.

[0051] Still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R _2a can be combined with any one or more embodiments of A, B, R ₁ , Ria, Rib, R ₂ , R ₃ , R ₃ a, R ₃ b, R _3c , L, Y, Z, Q, n, m, Rj _a , R ₄ ^ R-ic, Rid, R _4e> R4r, and R _4a .

[0052] Yet still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R ₃ can be combined with any one or more

embodiments of A, B, R ₁ , Ri _a , Rib, R2, R _2a , R3a, R _3b , R ₃ c, L, Y ₃ Z ₅ Q, n, m, R ₄₃ , R4 _b , R, _Cs R ₄ ^ R _4e , R4f, and R4 _g .

[0053] Other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R ₃₈ can be combined with any one or more embodiments of A, B, R], R) ₃₅ Rib, R ₂ , R ₂₃ , R3, R3b, R ₃ C, L, Y, Z ₅ Q ₅ n, m, R _4a , R4b, Ric, R _4d ,, Rte, R45 and R ₄₈ .

[0054] Still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R _3b can be combined with any one or more embodiments of A ₅ B, Ri, Ria, Rib, R2, R2a, R3, R3a, R3c L, Y ₅ Z ₅ Q ₅ n, m ₅ R _4a , R ₄ I,, R _4C R _4d ,, R ₄ ^ Rtf, and R ₄₆ .

[0055] Yet still other embodiments disclosed herein relate to a compound of Formula (I) ₅ in which any embodiment of R _3c can be combined with any one or more embodiments of A ₅ B, Ri, Ri _a , Rib, R2, R ₂ a, R3, R3a, R3b, L, Y ₅ Z ₅ Q ₅ n, m, R _4a , Rib, R ₄ C, R _4d ,,

[0056] Some embodiments disclosed herein relate to a compound of Formula (I) ₅ in which any embodiment of L can be combined with any one or more embodiments of A, B, Ri ₅ Ri ₈₅ R _1b , R ₂ , R2a, R3, Rsa, R ₃ b, R3c, Y, Z ₅ Q ₅ n ₅ m, R _4a , Rtb, Rtc, Rtd, R _4e , R4f, and R _4a .

[0057] Other embodiments disclosed herein relate to a compound of Formula (I) ₅ in which any embodiment of Y can be combined with any one or more embodiments of A ₅ B, Ri, R _{) a} , Rib, R2, R2a, R3, R3a, R ₃ b, R30 L, Z, Q ₃ n, m, R _4a , Rtb, Rtc, Rid, R^, R4f, and R ₄₆ .

[0058] Still other embodiments disclosed herein relate to a compound of Formula (1), in which any embodiment of Z can be combined with any one or more embodiments of A, B ₃ Ri ₃ R] ₃ , Rib, R ₂ , R _2a , R ₃ , R ₃ a, R ₃ b, R30, L, Y ₅ Q ₅ n, m, R _4a , R4b, R _4C , R»d, Rte, Rjf, and R ₄₆ .

[0059] Yet still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of Q can be combined with any one or more embodiments of A ₅ B ₅ Ri, Ri _a> Rib, R ₂ , R ₂ a, R3, R3a, R ₃ b, R ₃ c, L, Y, Z ₃ n, m, R _4a5 Rtb, Rtc, R _4d ,,

[0060] Some embodiments disclosed herein relate to a compound of Formula (I) ₅ in which any embodiment of n can be combined with any one or more embodiments of A, B, Ri, Ri ₃₅ Rib, R ₂ , R ₂₃ , R ₃ , R3a, R3b, R3c, L ₅ Y ₃ Z, Q ₅ m, R _4a , R ₄ b, Rtc, R _4d ,, R _4e , Rtf, and R ₄₅ .

(0061] Other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of m can be combined with any one or more embodiments of A ₅ B, R ₁ , R, _a , R| _b , R ₂ , R _2a , R ₃ , R ₃ a, R _3b , R ₃ C, U Y, Z ₅ Q, n, R _4a , R ₄₁ ,, R _4C , R^d, R ₄ -, IW, and R^.

[0062] Still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R _4a can be combined with any one or more embodiments of

A, B ₃ R ₁ , R _]a , Rib, R ₂ , R2a, R ₃ , R ₃ a, R ₃ b, R _3c , L, Y, Z, Q, n, m ₃ R ₄ I,, R _4C R ₄ Ci ₅ R _4e , R^, and R ₄₈ . ^'

[0063] Yet still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R4b can be combined with any one or more embodiments of A, B, R ₁ , R _{] a} , R, _b , R ₂ , R _2a , R ₃ , R ₃ a, R ₃ b, R _3c , L, Y, Z, Q, n, m, R _4a , R ₄₀ , R _4d , R ₄ C R45 and R ₄₈ .

[0064] Some embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R _4C can be combined with any one or more embodiments of A,

B, R ₁ , R _la , R, _b , R ₂ , R _2a , R ₃ , R ₃ a, R _3b , R _3c , L, Y ₅ Z ₅ Q, n, m, R _4a , R4 _b , R ₄₀ , R _4C , R _4C , and R ₄₆ .

[0065] Other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R ₄ Cj can be combined with any one or more embodiments of A, B, Ri, Ria, Rib, R ₂ , R _2a , R ₃ , R ₃ a, R3b, R _3c , L, Y ₅ Z ₅ Q, n, m, R _4a , R ₄ ^ R ₄ C, R _4e , R^f, and R^.

[0066] Still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of Ri _e can be combined with any one or more embodiments of

A, B, Rj ₅ Ria, R _Ib , R ₂ , R _2a , R ₃ , R ₃ a, R ₃ b, R ₃ C, L ₅ Y, Z ₅ Q, n, m, R _4a , R4b, R _4C R _4d ,, R ₄ ^ and R ₄₈ .

[0067] Yet still other embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R^r can be combined with any one or more embodiments of A ₅ B ₅ R _u R] ₈ , R _)b , R ₂ , R ₂₃ , R ₃ , R ₃ a, R _3b , R _3c , L, Y, Z, Q, n, m, R _4a , R-ib, R _4C , R _4d ,, ϊU _e , and R4g.

[0068] Some embodiments disclosed herein relate to a compound of Formula (I), in which any embodiment of R ₄ ^ can be combined with any one or more embodiments of A,

B, Ri, Ria, Rib, R2, R2a, R ₃ , R ₃ a, R ₃ b, R _3c , L ₅ Y, Z ₅ Q, n, m, R _4a , R _4b R ₄ C, R _4d ,, R _4e , and R ₄ ^

Definitions

[0069] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to

which this invention belongs. All patents, applications, published applications and other publications referenced herein are incorporated by reference in their entirety. In the event that there are plurality of definitions for a term herein, those in this section prevail unless stated otherwise

[0070] As used herein, any "R" group(s) such as, without limitation, Ri, Rι _a and Rib, represent substituents that can be attached to the indicated atom. A non-limiting list of R groups include hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and heteroalicyclyl. An .R group may be substituted or unsubstituted. If two "R" groups are covalently bonded to the same atom or to adjacent atoms, then they may be "taken together" as defined herein to form a cycloalkyl, aryl, heteroaryl or heteroalicyclyl group. For example, without limitation, if R _a and R _b of an NR ₃ R _b group are indicated to be "taken together", it means that they are covalently bonded to one another at their terminal atoms to form a ring that includes the nitrogen:

[0071] Whenever a group of this invention is described as being "optionally substituted" that group may be unsubstituted or substituted with one or more of the indicated substituents. Likewise, when a group is described as being "unsubstituted or substituted" if substituted, the substituent may be selected from one or mmore of the indicated substituents.

[0072] Unless otherwise indicated, when a substituent is deemed to be "optionally subsituted," or "substituted" it is meant that the subsitutent is a group that may be substituted with one or more group(s) individually and independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-suIfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. The protecting groups

that may form the protective derivatives of the above substituents are known to those of skill in the art and may be found in references Greene and Wuts, Protective Groups in Organic Synthesis, 3 ^rd Ed., John Wiley & Sons, New York, NY, 1999, which is hereby incorporated by reference in its entirety.

[0073] As used herein, "C _m to C _n " in which "m" and "n" are integers refers to the number of carbon atoms in an alkyl, alkenyl or alkynyl group or the number of carbon atoms in the ring of a cycloalkyl or cycloalkenyl group. That is, the alkyl, alkenyl, alkynyl, ring of the cycloalkyl or ring of the cycloalkenyl can contain from "m" to "n", inclusive, carbon atoms. Thus, for example, a "Ci to C ₄ alkyl" group refers to all alkyl groups having from 1 to 4 carbons, that is, CH ₃ -, CH ₃ CH ₂ -, CH ₃ CH ₂ CH ₂ -, (CH ₃ ) ₂ CH-, CH ₃ CH ₂ CH ₂ CH ₂ -, CH ₃ CH ₂ CH(CH ₃ )- and (CH ₃ ) ₃ C-. If no "m" and "n" are designated with regard to an alkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl group, the broadest range described in these definitions is to be assumed.

[0074] As used herein, "alkyl" refers to a straight or branched hydrocarbon chain fully saturated (no double or triple bonds) hydrocarbon group. The alkyl group may have 1 to 20 carbon atoms (whenever it appears herein, a numerical range such as "1 to 20" refers to each integer in the given range; e.g., "1 to 20 carbon atoms" means that the alkyl group may consist of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, etc. , up to and including 20 carbon atoms, although the present definition also covers the occurrence of the term "alkyl" where no numerical range is designated). The alkyl group may also be a medium size alkyl having 1 to 10 carbon atoms. The alkyl group could also be a lower alkyl having 1 to 5 carbon atoms. The alkyl group of the compounds may be designated as "C ₁ -C ₄ alkyl" or similar designations. By way of example only, "Ci-C ₄ alkyl" indicates that there are one to four carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and t-butyl. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, piopenyl, butenyl, and the like.

[0075] The alkyl group may be substituted or unsubstituted. When substituted, the substituent grouρ(s) is(are) one or more group(s) individually and independently selected from alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl,

aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. Wherever a substituent is described as being "optionally substituted" that substitutent may be substituted with one of the above substituents.

[0076] As used herein, "alkenyl" refers to an alkyl group that contains in the straight or branched hydrocarbon chain one or more double bonds. An alkenyl group of this invention may be unsubstituted or substituted. When substituted, the substituent(s) may be selected from the same groups disclosed above with regard to alkyl group substitution.

[0077] As used herein, "alkynyl" refers to an alkyl group that contains in the straight or branched hydrocarbon chain one or more triple bonds. An alkynyl group of this invention may be unsubstituted or substituted. When substituted, the substituent(s) may be selected from the same groups disclosed above with regard to alkyl group substitution.

[0078] As used herein, "aryl" refers to a carbocyclic (all carbon) ring or two or more fused rings (rings that share two adjacent carbon atoms) that have a fully delocalized pi- electron system. Examples of aryl groups include, but are not limited to, benzene, naphthalene and azulene. An aryl group of this invention may be substituted or unsubstituted. When substituted, hydrogen atoms are replaced by substituent group(s) that is(are) one or more group(s) independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C- carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and

amino, including mono- and di-substituted amino groups, and the protected derivatives thereof.

[0079] As used herein, "heteroaryl" refers to a monocyclic or multicyclic aromatic ring system (a ring system with fully delocalized pi-electron system), one or two or more fused rings that contain(s) one or more heteroatoms, that is, an element other than carbon, including but not limited to, nitrogen, oxygen and sulfur. Examples of heteroaryl rings include, but are not limited to, furan, thiophene, phthalazine, pyrrole, oxazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, triazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine and triazine. A heteroaryl group of this invention may be substituted or unsubstituted. When substituted, hydrogen atoms are replaced by substituent group(s) that is(are) one or more group(s) independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterόalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyi)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesulfonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof.

[0080] An "aralkyl" is an aryl group connected, as a substituent, via a lower alkylene group. The lower alkylene and aryl group of an aralkyl may be substituted or unsubstituted. Examples include but are not limited to benzyl, substituted benzyl, 2- phenylethyl, 3-phenylpropyl, and naphtylalkyl.

[0081] A "heteroaralkyl" is heteroaryl group connected, as a substituent, via a lower alkylene group. The lower alkylene and heteroaryl group of heteroaralkyl may be substituted or unsubstituted. Examples include but are not limited to 2-thienylmethyl, 3- thienylmethyl, furylmethyl, thienylethyl, pyrrolylalkyl, pyridylalkyl, isoxazollylalkyl, and imidazolylalkyl, and their substituted as well as benzo-fused analogs.

[0082] "Lower alkylene groups" are straight-chained tethering groups, forming bonds to connect molecular fragments via their terminal carbon atoms. Examples include but

are not limited to methylene (-CH ₂ -), ethylene (-CH ₂ CH ₂ -), propylene (-CH ₂ CH ₂ CH ₂ -), and butylene (-(CH ₂ ^-) groups. A lower alkylene group may be substituted or unsubstituted.

[0083] As used herein, "alkylidene" refers to a divalent group, such as =CR'R", which is attached to one carbon of another group, forming a double bond, Alkylidene groups include, but are not limited to, methylidene (=CH ₂ ) and ethylidene (=CHCH ₃ ). As used herein, "arylalkylidene" refers to an alkylidene group in which either R' and R" is an aryl group. An alkylidene group may be substituted or unsubstituted.

[0084] As used herein, "alkoxy" refers to the formula —OR wherein R is an alkyl is defined as above, e.g. methoxy, ethoxy, n-propoxy, 1 -methylethoxy (isopropoxy), n- butoxy, iso-butoxy, sec-butoxy, tert-butoxy, amoxy, tert-amoxy and the like. An alkoxy may be substituted or unsubstituted.

[0085] As used herein, "alkylthio" refers to the formula -SR wherein R is an alkyl is defined as above, e.g. methylmercapto, ethylmercapto, n-propylmercapto, 1- methylelhylmercapto (isopropylmercapto), n-butylmercapto, iso-butylmercapto, sec- butylmercapto, tert-butylmercapto, and the like. An alkylthio may be substituted or unsubstituted.

[0086] As used herein, "aryloxy" and "arylthio" refers to RO- and RS-, in which R is an aryl, such as but not limited to phenyl. Both an aryloxyl and arylthio may be substituted or unsubstituted.

[0087] As used herein, "acyl" refers to a hydrogen, alkyl, alkenyl, alkynyl, or aryl connected, as substituents. via a carbonyl group. Examples include formyl, acetyl, propanoyl, benzoyl, and acryl. An acyl may be substituted or unsubstituted. An acyl may be substituted or unsubstituted.

[0088] As used herein, "cycloalkyl" refers to a completely saturated (no double bonds) mono- or multi- cyclic hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro-connected fashion. Cycloalkyl groups of this invention may range from C3 to C 10, in other embodiments it may range from C ₃ to Cβ. A cycloalkyl group may be unsubstituted or substituted. Typical cycloalkyl groups include, but are in no way limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. If substituted, the substituent(s) may be an alkyl or selected from

those indicated above with regard to substitution of an alkyl group unless otherwise indicated.

[0089J As used herein, "cycloalkenyl" refers to a cycloalkyl group that contains one or more double bonds in the ring although, if there is more than one, they cannot form a fully delocalized pi-electron system in the ring (otherwise the group would be "aryl," as defined herein). When composed of two or more rings, the rings may be connetected together in a fused, bridged or spiro-connected fashion. A cycloalkenyl group of this invention may be unsubstituted or substituted. When substituted, the substituent(s) may be an alkyl or selected from the groups disclosed above with regard to alkyl group substitution unless otherwise indicated.

[0090] As used herein, "cycloalkynyl" refers to a cycloalkyl group that contains one or more triple bonds in the ring. When composed of two or more rings, the rings may be joined together in a fused, bridged or spiro-connected fashion. A cycloalkynyl group of this invention may be unsubstituted or substituted. When substituted, the substituent(s) may be an alkyl or selected from the groups disclosed above with regard to alkyl group substitution unless otherwise indicated.

[0091] A "(cycloalkyl)alkyP' is a cycloalkyl group connected, as a substituent, via a lower alkylene group. The lower alkylene and cycloalkyl of a (cycloalkyl)alkyl may be substituted or unsubstituted. Examples include but are not limited cyclopropylmethyl, cyclobutylmethyl, cyclopropylethyl, cyclopropylbutyl, cyclobutylethyl, cyclopropylisopropyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, cycloheptylmethyl, and the like.

[0092] A "(cycloalkenyl)alkyl" is a cycloalkenyl group connected, as a substituent, via a lower alkylene group. The lower alkylene and cycloalkenyl of a (cycloalkenyl)alkyl may be substituted or unsubstiluted.

[0093] A "(cycloalkynyl)alkyP' is a cycloalkynyl group connected, as a substituent, via a lower alkylene group. The lower alkylene and cycloalkynyl of a (cycloalkynyl)alkyl may be substituted or unsubstituted.

[0094] As used herein, "heteroalicyclic" or "heteroalicyclyl" refers to a stable 3- to 18 membered ring which consists of carbon atoms and from one to five heteroatoms

selected from the group consisting of nitrogen, oxygen and sulfur. For the purpose of this invention, the "heteroalicyclic" or "heteroalicyclyl" may be monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may be joined together in a fused, bridged or spiro-connected fashion; and the nitrogen, carbon and sulfur atoms in the "heteroalicyclic" or "heteroalicyclyl" may be optionally oxidized; the nitrogen may be optionally quaternized; and the rings may also contain one or more double bonds provided that they do not form a fully delocalized pi-electron system throughout all the rings. Heteroalicyclyl groups of this invention may be unsubstituted or substituted. When substituted, the substituent(s) may be one or more groups independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, heteroaralkyl, (heteroalicyclyl)alkyl, hydroxy, protected hydroxyl, alkoxy, aryloxy, acyl, ester, mercapto, alkylthio, arylthio, cyano, halogen, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, C-carboxy, protected C-carboxy, O-carboxy, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, haloalkyl, haloalkoxy, trihalomethanesulfonyl, trihalomethanesuifonamido, and amino, including mono- and di-substituted amino groups, and the protected derivatives thereof. Examples of such "heteroalicyclic" or "heteroalicyclyl" include but are not limited to, azepinyl, acridinyl, carbazolyl, cinnolinyl, dioxolanyl, imidazolinyl, morpholinyl, oxiranyl, piperidinyl iV-Oxide, piperidinyl, piperazinyl, pyrrolidinyl, 4-piperidonyl, pyrazolidinyl, 2-oxopyrrolidinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, and thiamorpholinyl sulfone.

[0095] An "(heteroalicyclyl)alkyP' is a heterocyclic or a heterocyclyl group connected, as a substituent, via a lower alkylene group. The lower alkylene and heterocyclic or a heterocyclyl of a (heteroalicyclyl)alkyl may be substituted or unsubstituted. Examples include but are not limited 4-methyltetrahydro-2H-pyran, substituted 4-methyltetrahydro-2H- pyran, 4-ethylpiperidine, 4-propylpiperidine, 4-methyltetrahydro-2H-thioρyran. and 4-methyl- 1 ,3-thiazinane.

[0096] As used herein, "halo" or "halogen" refers to F (fluoro), Cl (chloro), Br (bromo) or I (iodo).

(0097] As used herein, "haloalkyl" refers to an alkyl group in which one or more of the hydrogen atoms are replaced by halogen. Such groups include but are not limited to, chloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl and 1 -chloro-2-fluoromethyl, 2- fluoroisobutyl. A haloalkyl may be substituted or unsubstituted.

[0098] As used herein, "haloalkoxy" refers to an "RO-" group in which R is a haloalkyl group. Such groups include but are not limited to, chloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy and l-chloro-2 -fluoromethoxy, 2-fluoroisobutyoxy. A haloalkoxy may be substituted or unsubstituted.

[0099] An "O-carboxy" group refers to an "RC(=O)O-" group in which R can be hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heteroalicyclyl, aralkyl, or (heteroalicyclyl)alkyl, as defined herein. An O-carboxy may be substituted or unsubstituted.

[0100] A "C-carboxy" group refers to a "-C(=O)R" group in which R can be the same as defined with respect to O-carboxy. A C-carboxy may be substituted or unsubstituted.

[0101] A "trihalomethanesulfonyl" group refers to an "X3CSO2-" group wherein X is a halogen.

[0102] A "cyano" group refers to a "-CN" group.

[0103] An "isocyanato" group refers to an "-NCO" group.

[0104] A "thiocyanato" group refers to a "-CNS" group.

[0105] An "isothiocyanato" group refers to an " -NCS" group.

[0106] A "sulfinyl" group refers to an "-S(=O)-R" group in which R can be the same as defined with respect to O-carboxy. A sulfinyl may be substituted or unsubstituted.

[0107] A "sulfonyl" group refers to an "SO ₂ R" group in which R can be the same as defined with respect to O-carboxy. A sulfonyl may be substituted or unsubstituted.

[0108] An "S-sulfonamido" group refers to an "-SO ₂ NRARB" group in which R _A and R _B can be the same as defined with respect to O-carboxy. An S-sulfonamido may be substituted or unsubstituted.

[0109] An "N-sulfonamido" group refers to an "RSO ₂ N(R _A )-" group in which R and R _A can be the same as defined with respect to O-carboxy. A sulfonyl may be substituted or unsubstituted.

|0110] A "trihalomethanesulfonamido" group refers to an "X ₃ CSO ₂ N(R)-" group with X as halogen and R can be the same as defined with respect to O-carboxy. A trihalomethanesulfonamido may be substituted or unsubstituted.

(0111] An "O-carbamyl" group refers to an "-OC(=O)NR _A RB" group in which R _A and R _B can be the same as defined with respect to O-carboxy. An O-carbamyl may be substituted or unsubstituted.

[0112] An "N-carbamyl" group refers to an "ROC(=O)NR _A -" group in which R and R _A can be the same as defined with respect to O-carboxy. An N-carbamyl may be substituted or unsubstituted.

|0113] An "O-thiocarbamyl" group refers to an "-OC(=S)-NR _A R _B " group in which R _A and R _B can be the same as defined with respect to O-carboxy. An O-thiocarbamyl may be substituted or unsubstituted.

[0114] An "N-thiocarbamyl" group refers to an "ROC(=S)NR _A -" group in which R and R _A can be the same as defined with respect to O-carboxy . An N-thiocarbamyl may be substituted or unsubstituted.

[0115] A "C-amido" group refers to a "-C(=O)NR _A R _B " group in which R _A and R _B can be the same as defined with respect to O-carboxy. A C-amido may be substituted or unsubstituted.

[0116] An "N-amido" group refers to an "RC(=O)NR _A -" group in which R and R _A can be the same as defined with respect to O-carboxy. An N-amido may be substituted or unsubstituted.

[0117] An "ester" refers to a "-C(=O)OR" group in which R can be the same as defined with respect to O-carboxy. An ester may be substituted or unsubstituted.

[0118] As used herein, an "amide" refers to a "— C(=O)NR _A R _B " group in which R _A and R _B can be the same as R defined with respect to O-carboxy.

[0119] Any unsubstituted or monosubstituted amine group on a compound herein can be converted to an amide, any hydroxyl group can be converted to an ester and any carboxyl group can be converted to either an amide or ester using techniques well-known to those skilled in the art (see, for example, Greene and Wuts, Protective Groups in Organic Synthesis, 3 ^rd Ed., John Wiley & Sons, New York, NY ₅ 1999).

[0120] Where the numbers of substituents is not specified (e.g. haloalkyl), there may be one or more substituents present. For example "haloalkyl" may include one or more of the same or different halogens. As another example, "C1-C3 alkoxy phenyl" may include one or more of the same or different alkoxygroups containing one, two or three atoms.

[0121] As used herein, the abbreviations for any protective groups, amino acids and other compounds, are, unless indicated otherwise, in accord with their common usage, recognized abbreviations, or the IUPAC-IUB Commission on Biochemical Nomenclature (See, Biochem. 1 1 :942-944 (1972)).

[0122] As employed herein, the following terms have their accepted meaning in the chemical literature.

AcOH Acetic acid anhyd anhydrous

CDI 1 , 1 '-carbonyldiimidazole

DCM Dich loromethane

DMF N, N-Dimethy lformamide

DMAP 4-Dimethylaminopyridine

DMSODimethyl sulfoxide

EDCl 1 -(3-Dimethylaminopropyl)-3-ethylcarbodiirnide hydrochloride

Et ₂ O Diethyl ether

EtOAc Ethyl acetate

EtOH Ethanol

MeOH Methanol

MeCN Acetonitrile

NH ₄ OAc Ammonium acetate

NMM ./V-Methylmorpholine

HOBt 1 -Hodroxybenztriazole

Pd/C Palladium on activated carbon

TEA Triethylamine

THF Tetrahydrofuran uW, MW Microwave reactor chemistry

[0123] It is understood that, in any compound of this invention having one or more chiral centers, if an absolute stereochemistry is not expressly indicated, then each center may independently be of R-configuration or S-configuration or a mixture thereof. Thus, the compounds provided herein may be enatiomerically pure or be stereoisomeric or diastereomeric mixtures. In addition it is understood that, in any compound of this invention having one or more double bond(s) generating geometrical isomers that can be defined as E or Z each double bond may independently be E or Z a mixture thereof. Likewise, all tautomeric forms are also intended to be included.

[0124] As used herein, "pharmaceutically acceptable salt" refers to a salt of a compound that does not abrogate the biological activity. and properties of the compound. Pharmaceutical salts can be obtained by reaction of a compound disclosed herein with an acid or base. Base-formed salts include, without limitation, ammonium salt (NH ₄ ⁴ ); alkali metal, such as, without limitation, sodium or potassium, salts; alkaline earth, such as, without limitation, calcium or magnesium, salts; salts of organic bases such as, without limitation, dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylarnine; and salts with the amino group of amino acids such as, without limitation, arginine and lysine. Useful acid- based salts include, without limitation, hydrochlorides, hydrobromides, sulfates, nitrates, phosphates, methanesulfonates, ethanesulfonates, p-toluenesulfonates and salicylates.

[0125] Pharmaceutically acceptable solvates and hydrates are complexes of a compound with one or more solvent of water molecules, or 1 to about 100, or 1 to about 10, or one to about 2, 3 or 4, solvent or water molecules.

[0126] As used herein, a "prodrug" refers to a compound that may not be pharmaceutically active but that is converted into an active drug upon in vivo administration. The prodrug may be designed to alter the metabolic stability or the transport characteristics of a drug, to mask side effects or toxicity, to improve the flavor of a drug or to alter other characteristics or properties of a drug. Prodrugs are often useful because they may be easier to administer than the parent drug. They may, for example, be bioavailable by oral administration whereas the parent drug is not. The prodrug may also have better solubility than the active parent drug in pharmaceutical compositions. An example, without limitation, of a prodrug would be a compound disclosed herein, which is administered as an ester (the

"prodrug") to facilitate absorption through a cell membrane where water solubility is detrimental to mobility but which then is metabolically hydrolyzed to a carboxylic acid (the active entity) once inside the cell where water-solubility is beneficial. A further example of a prodrug might be a short peptide (polyaminoacid) bonded to an acid group where the peptide is metabolized in vivo to release the active parent compound. By virtue of knowledge of pharmacodynamic processes and drug metabolism in vivo, those skilled in the art, once a pharmaceutically active compound is known, can design prodrugs of the compound (see, e.g. Nogrady (1985) Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, pages 388-392)

[0127J As used herein, the term "complement" refers to a oligonucleotide or polynucleotide that hybridizes by base-pairing, adenine to tyrosine and guanine to cytosine, to another oligonucleotide.

[0128] As used herein, to "modulate" the activity of a Ghrelin receptor means either to activate it, i.e., to increase its cellular function over the base level measured in the particular environment in which it is found, or deactivate it, i.e., decrease its cellular function to less than the measured base level in the environment in which it is found and/or render it unable to perform its cellular function at all, even in the presence of a natural binding partner. A natural binding partner is an endogenous molecule that is an agonist for the receptor.

[0129] As used herein, to "detect" changes in the activity of a Ghrelin receptor or of a Ghrelin receptor sub-type refers to the process of analyzing the result of an experiment using whatever analytical techniques are best suited to the particular situation. In some cases simple visual observation may suffice, in other cases the use of a microscope, visual or UV light analyzer or specific protein assays may be required. The proper selection of analytical tools and techniques to detect changes in the activity of a Ghrelin receptor or a Ghrelin receptor sub-type are well-known to those skilled in the art.

[0130] An "agonist" is defined as a compound that increases the basal activity of a receptor (i.e. signal transduction mediated by the receptor).

[0131] As used herein, "partial agonist" refers to a compound that has an affinity for a receptor but, unlike an agonist, when bound to the receptor it elicits only a fractional

degree of the pharmacological response normally associated with the receptor even if a large number of receptors are occupied by the compound.

[0132] An "inverse agonist" is defined as a compound, which reduces, or suppresses the basal activity of a receptor, such that the compound is not technically an antagonist but, rather, is an agonist with negative intrinsic activity.

[0133] As used herein, "antagonist" refers to a compound that binds to a receptor to form a complex that does not give rise to any response, as if the receptor was unoccupied. An antagonist attenuates the action of an agonist on a receptor. An antagonist may bind reversibly or irreversibly, effectively eliminating the activity of the receptor permanently or at least until the antagonist is metabolized or dissociates or is otherwise removed by a physical or biological process.

[0134] As used herein, "IC ₅₀ " refers to an amount, concentration of dosage of a particular test compound that achieves a 50% inhibition of a maximal response, such as modulation of GPCR, including Ghrelin receptor, activity, in an assay that measures such response in an assay that measures such response for example but not limited to R-SAT® described herein.

[0135] As used herein, "EC ₅₀ " refers to an dosage, concentration or amount of a particular test compound that elicits a dose-dependent respons at 50% of maximal expression of a particular response that is induced, provoked or potentiated by the particular test compound, in an assay that measures such response for example but not limited to R-SAT® described herein.

[0136] The term "therapeutically effective amount" is used to indicate an amount of an active compound, or pharmaceutical agent, that elicits the biological or medicinal response indicated. This response may occur in a tissue, system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, and includes alleviation of the symptoms of the disease being treated.

[0137] As used herein, a "subject" refers to an animal that is the object of treatment, observation or experiment. "Animal" includes cold- and warm-blooded vertebrates and invertebrates such as fish, shellfish, reptiles and, in particular, mammals. "Mammal" includes, without limitation, mice; rats; rabbits; guinea pigs; dogs; cats; sheep;

goats; cows; horses; primates, such as monkeys, chimpanzees, and apes, and, in particular, humans.

[0138] As used herein, a "patient" refers to a subject that is being treated in order to attempt to cure, or at least ameliorate the effects of, a particular disease or disorder or to prevent the disease or disorder from occurring in the first place.

(0139] As used herein, the terms "treating," "treatment," "therapeutic," or "therapy" do not necessarily mean total cure or abolition of the disease or condition. Any alleviation of any undesired signs or symptoms of a disease or condition, to any extent can be considered treatment or therapy. Furthermore, treatment may include acts that may worsen the patient's overall feeling of well-being or appearance.

[0140] As used herein, a "carrier" refers to a compound that facilitates the incorporation of a compound into cells or tissues. For example, without limitation, dimethyl sulfoxide (DMSO) is a commonly utilized carrier that facilitates the uptake of many organic compounds into cells or tissues of a subject. fO141] As used herein, a "diluent" refers to an ingredient in a pharmaceutical composition that lacks pharmacological activity but may be pharmaceutically necessary or desirable. For example, a diluent may be used to increase the bulk of a potent drug whose mass is too small for manufacture or administration. It may also be a liquid for the dissolution of a drug to be administered by injection, ingestion or inhalation. A common form of diluent in the art is a buffered aqueous solution such as, without limitation, phosphate buffered saline that mimics the composition of human blood.

[0142] As used herein, an "excipient" refers to an inert substance that is added to a pharmaceutical composition to provide, without limitation, bulk, consistency, stability, binding ability, lubrication, disintegrating ability etc., to the composition. A "diluent" is a type of excipient.

Synthesis

[0143] General synthetic routes to the compounds of this invention are shown in Scheme 1-1 1. The routes shown are illustrative only and are not intended, nor are they to be construed, to limit the scope of this invention in any manner whatsoever. Those skilled in the

art will be able to recognize modifications of the disclosed synthesis and to devise alternate routes based on the disclosures herein; all such modifications and alternate routes are within the scope of this invention.

Scheme 1 : Attachmet of a linker to the indole core

Scheme 2: Aluminium mediated 3-acylation on an indole

Scheme 3 : Amide coupling on an indole

Scheme 4: Magnesium catalyzed 3-carboxy animation on an indole

Scheme 5: Mitsunobu coupling of a phenol

Scheme 6: Magnesium catalyzed 3-acylation on an indole

Scheme 7: N-alkylation of secondary amines

H R ¹¹¹ HaI, Cs ₂ CO ₃ R-

R ¹ R" MeCN R- ¹ ^R" 60 ⁰ C, 16h

Scheme 8: Ketone synthesis via a Weinreb amide

Scheme 9: Reduction of a aryl alkyl ketone

Scheme 10: General synthesis of examples and library compounds

Scheme 1 1 : Formation of Weinrebamide on an indole

Methods of Use

[0144] Some embodiments disclosed herein relate to methods for treating or preventing diseases or conditions by administering one or more compounds of Formula I and/or a compound described herein. A non-limiting list of diseases or conditions include but are not limited to obesity, an obesity-associated disorder, a metabolic disorder, metabolic syndrome, an endocrine disorder, an appetite disorder, an eating disorder, an eating disorder requiring appetite control, atherosclerosis, diabetes, diabetes mellitus, high cholesterol, hyperlipidemia, cachexia, anorexia, bulimia, inflammation, a chronic inflammatory disorder, rheumatoid arthritis, asthma, psoriasis, a cardiovascular disorder, angina, cardiac ischemia, cardiac failure, heart disease, congestive heart failure, ischemic heart disease, chronic heart disease, hemorrhagic shock, septic shock, cirrhosis, a neurological disorder, anxiety, depression, an attention deficit disorder, a memory disorder, a cognitive disorder, a gastrointestinal disorder, reduced gastric motility, reduced gastric and intestinal motility, excessive gastric motility, post-operative gastric ileus, delayed gastric emptying, delayed gastric emptying due to diabetes, delayed gastric emptying post-operatively, short bowel syndrome, a gastric ulcer, nausea, emesis, diarrhea, gastroparesis, diabetic gastroparesis, opioid-induced bowel dysfunction, chronic intestinal pseudoobstruction, a sleep disorder, insomnia, a hyperproliferative disorder cancer cancer cachexia dwarfism, osteoporosis, a

catabolic state, somatopause, osteopenia, a disorder of the pancreas, a hormone deficiency, gastrointestinal dumping syndrome, postgastroenterectomy syndrome, celiac disease, AIDS, wasting, age-related decline in body composition, hypertension, retinopathy, dyslipidemia, a gall stone, osteoarthritis, congestive heart failure, insulin resistance, burn, wound, protein loss, sexual dysfunction, a central nervous system disorder, a genetic disorder, irritable bowel syndrome (IBS), non-ulcer dyspepsia, Crohn's disease, a gastroesophogeal reflux disorder, constipation, ulcerative colitis, pancreatitis, infantile hypertrophic pyloric stenosis, carcinoid syndrome, malabsorption syndrome, atrophic colitis, gastritis, gastric stasis, frailty, acromegaly, and protein loss.

[0145] Other embodiments disclosed herein relate to methods for treating impaired or risk of impaired wound healing, impaired or risk of impaired recovery from burns, impaired or risk of impaired recovery from surgery, impaired or risk of impaired muscle strength, impaired or risk of impaired mobility, altered or risk of altered skin thickness, impaired or risk of impaired metabolic homeostasis, or impaired or risk of impaired renal homeostasis.

[0146] Still other embodiments disclosed herein relate to methods for facilitating neonatal development, stimulating growth hormone release in humans, maintaining muscle strength and function in humans, reversing or preventing of frailty in humans, preventing of catabolic side effects of glucocorticoids, treating osteoporosis, stimulating and increasing muscle mass and/or muscle strength, stimulating the immune system, attenuating protein catabolic response, accelerating wound healing, accelerating bone fracture repair, treating renal failure or insufficiencies resulting in growth retardation, treating short stature, treating obesity and growth retardation, accelerating the recovery and reducing hospitalization of burn patients, treating intrauterine growth retardation, treating skeletal dysphasia, treating hypercortisolism, treating Cushing's syndrome, inducing pulsatile growth hormone release, replacing growth hormone in stressed patients, treating osteochondrodysplasias, treating Noonans syndrome, treating schizophrenia, treating depression, treating Alzheimer's disease, treating emesis, treating memory loss, treating reproduction disorders, treating delayed wound healing, treating psychosocial deprivation, treating pulmonary dysfunction, treating ventilator dependency; attenuating protein catabolic response, reducing cachexia and protein

loss, treating hyperinsulinemia, improving ovulation induction, stimulating thymic development, preventing thymic function decline, treating immunosuppressed patients, improving muscle mobility, maintaining skin thickness, promoting metabolic homeostasis, promoting renal homeostasis, stimulating osteoblasts, stimulating bone remodeling, stimulating cartilage growth, stimulating the immune system in companion animals, treating disorders of aging in companion animals, promoting growth in livestock, and/or stimulating wool growth in sheep.

[0147] In one embodiment, a method of treating or preventing a disorder or condition comprises administering to a subject a therapeutically effective amount of a compound of Formula I and/or a compound described herein, for the purpose of alleviating and/or controlling the symptoms associated with these disorders or conditions.

[0148] In still another embodiment, the compound of Formula I and/or a compound described herein can modulate, agonize, inverse agonize, and/or antagonize a ghrelin receptor. In some embodiments, the compound of Formula I and/or a compound described herein can inverse agonize, and/or antagonize a ghrelin receptor.

[0149] Some embodiments described herein relate to the treatment of an eating disorder or condition related to an eating disorder. Treatment of eating disorders can include controlling the symptoms observed during these disorder or conditions, such as, for example, increased appetite and binge eating. In one embodiment, a method of treating an eating disorder or condition comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein, to a subject for the purpose of treating eating disorders requiring appetite control. In another embodiment, a method of treating an eating disorder or condition comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating a subject suffering from a symptom of an eating disorder requiring appetite control. In still another embodiment, a method of treating an eating disorder or condition comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating obesity and disorders associated with obesity. A non-limiting list of eating disorders and conditions associated with eating disorders includes obesity, metabolic syndrome, appetite disorders,

cachexia, anorexia, bulemia, high cholesterol, hyperlipidemia, heart disease, atherosclerosis, and diabetes.

[0150] ' Other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula 1 and/or a compound described herein to a subject for the purpose of promoting weight loss in a subject in need thereof. Promotion of weight loss can include reversing anabolic states.

[0151] Still other embodiments described herein relate to a method of preventing weight gain or weight loss in a subject comprising administering to a subject a therapeutically effective amount of a compound of Formula 1 and/or a compound described herein. Weight gain can be caused from a medication the subject is taking such as insulin, thiazolidinedione, sulfonylurea, corticosteroid, progestational steroid, antihistamine, alpha-adrenergic blocker, beta-adrenergic blocker, an antidepressant (e.g., a tricyclic antidepressant, selective serotonin reuptake inhibitor, a monoamine inhibitor, lithium), antipsychotic, and anticonvulsant. Weight loss can be caused by chemotherapy, radiation therapy, temporary immobilization, permanent immobilization or dialysis. In one embodiment, the compound of Formula I and/or a compound described herein can be used to prevent weight gain following weight loss by a subject.

J0152] Yet still other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of maintaining the weight of a subject in need thereof.

[0153] Some embodiments disclosed herein relate to a method for the treatment of post-operative ileus and/or cachexia comprising comprise administering to the subject a pharmaceutically effective amount of a compound of Formula 1 and/or a compound described herein. Causes of post-operative ileus and/or cachexia include but are not limited to cancer, AIDS, cardiac disease and renal disease, gastroparesis, such as that resulting from type I or type II diabetes, other gastrointestinal disorders, growth hormone deficiency, bone loss, and other age-related disorders.

[0154] Other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a

compound described herein to a subject for the purpose of treating a gastrointestinal disorder. Treatment of gastrointestinal disorders can include reversing the symptoms observed with these syndromes. Such symptoms can include loss of gastric motility or excessive gastric motility. Gastrointestinal disorders treatable by the methods of the present invention include, but are not limited to, reduced gastric and intestinal motility, post-operative gastric ileus, delayed gastric emptying, delayed gastric emptying due to diabetes, delayed gastric emptying post-operatively, short bowel syndrome, a gastric ulcer, nausea, emesis, and/or diarrhea.

[0155] Yet other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating a cardiovascular disorder. Cardiovascular disorders treatable by the methods of the present invention include, but are not limited to, angina, cardiac ischemia, cardiac failure, heart disease, and related vascular disorders like atherosclerosis. In another embodiment, the methods of the present invention can also be effective in reducing cardiac afterload and/or increasing cardiac output.

[0156] Yet still other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating a sleep disorder such as insomnia or narcolepsy. In one embodiment, the methods of improving sleep architecture, facilitating induction of sleep, and/or improving the quality of sleep comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject. In another embodiment, the methods of improving sleep architecture, facilitating induction of sleep, and/or improving the quality of sleep comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein, and a sleep agent such as ambien®, lunesta®, doxepin, indiplon, gaboxadol, and N- (4-fluorobenzy I)-N-(I -methylpiperdin -4-yl)-N'-(4-(2- methylproploxy)phenylmethyl)carbamide. In still another embodiment, the method for maintaining the sleep of a subject comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein. In yet still another embodiment, the method for maintaining the sleep of a subject comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described

herein in combination with a sleep agent (e.g, ambien®, lunesta®, doxepin, indiplon, gaboxadol, and N-(4-fluorobenzyl)-N-(l-methylpiperdin -4-yl)-N'-(4-(2- methylproploxy)phenylmethyl)carbamide. In one embodiment, the method for facilitating alertness or awakefulness comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein. In another embodiment, the method for facilitating alertness or wakefulness comprises administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject, wherein the subject can be taking an agent that causes drowsiness or induces sleep (e.g., a sedative, ambien®, lunesta®, doxepin, or gaboxadol).

[0157J Some embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating a hyperproliferative disorder such as a tumor, cancer, and a neoplastic disorder, as well as a premalignant and non-neoplastic or non-malignant hyperproliferative disorder. In another embodiment, the methods of the present invention can also be effective in controlling unwanted cellular proliferation associated with a cancer. A non-limiting list of hyperproliferative disorders include but are not limited to malignant disorders such as breast cancers, osteosarcomas, angiosarcomas, fibrosarcomas and other sarcomas, leukemias, lymphomas, sinus tumors, ovarian cancers, uretal cancers, bladder cancers, prostate cancers, other genitourinary cancers, colon cancers, esophageal cancers, stomach cancers, other gastrointestinal cancers, lung cancers, myelomas, pancreatic cancers, liver cancers, kidney cancers, endocrine cancers, gliomas, neuroblastomas, skin cancers, brain cancers, and central and peripheral nervous (CNS) system tumors.

[0158] Other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of diagnosing a hormone deficiency (e.g., production of a growth hormone, ACTH, Cortisol, insulin-like growth factor 1 (IGF-I), and/or prolactin) In another embodiment, the methods of the present invention can also be effective in modulating hormone production.

[0159] Yet other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating a hormone deficiency. Hormone deficiency disorders treatable by the methods of the present invention include, but are not limited to, deficiencies in producing growth hormone, ACTH, Cortisol, insulin-like growth factor 1 (IGF-I), and/or prolactin.

[0160] Yet still other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating dwarfism, osteoporosis, a catabolic state, somatopause, and/or osteopenia.

[0161] Some embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating a disorder of the pancreas.

[0162] Other embodiments described herein relates to a method of controlling the level of glucose in a subject comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject.

[0163] Yet other embodiments described herein relates to a method of treating diabetes in a subject comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject.

[0164] Yet still other embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a compound described herein to a subject for the purpose of treating a neurological disorder, anxiety, depression, an attention deficit disorder, a memory disorder, and/or a cognitive disorder. In another embodiment, the methods of the present invention can also be effective in relieving symptoms of anxiety and/or improving memory. In one embodiment, a compound of Formula I and/or a compound described herein can be used to alleviate or treat a symptom associated with a neurological disorder comprising administering to a subject with altered cognition a compound of Formula I and/or a compound described herein.

[0165] Some embodiments described herein relate to methods comprising administering a therapeutically effective amount of a compound of Formula I and/or a

compound described herein to a subject for the purpose of treating inflammation. The causes of the inflammation include but are not limited to a chronic inflammatory disorder, rheumatoid arthritis, asthma, an allergy, and/or psoriasis.

[0166] Other embodiments disclosed herein relate to methods for treating diseases or conditions by administering one or more compounds of Formula I and/or a compound described herein comprising identifying a subject in need of treatment or prevention and administering to the subject a therapeutically effective amount of a compound of Formula I and/or a compound described herein.

(0167] One embodiment described herein relates a method of identifying a compound which regulates activity of the Ghrelin receptor by culturing cells that express the Ghrelin receptor; incubating the cells with at least one compound of Formula I and/or a compound described herein as defined herein; and determining any change in activity of the Ghrelin receptor so as to identify a compound of Formula I and/or a compound described herein which regulates activity of the Ghrelin receptor.

[0168] In any of the methods described herein, in some embodiments, the compound of Formula (I) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, has the structure described herein provided that when R ₂ and R. _2a are taken together, along with the nitrogen atom to which they are attached, form a

substituted heteroalicyclyl, wherein the substituted heteroalicyclyl is substituted with n- butyl at the para-position, then B cannot be selected from the group consisting of methyl, - C(=O)Ri, and -CH ₂ OH, wherein Ri is hydrogen or methyl; or A cannot be methyl. In any of the methods described herein, in other embodiments, the compound of Formula (I) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, has the structure described herein provided that when R ₂ and R _2a are taken together, along with the nitrogen atom to which they are attached, form a substituted heteroalicyclyl, wherein

the substituted heteroalicyclyl is ^~^ substituted with an alkyl, such as n-butyl, then A, R ₃ ,

R-3 _a5 R _3b , and R _3c cannot all be hydrogen. In any of the methods described herein, in some embodiments, the compound of formula I can be selected from the group consisting of:

Pharmaceutical Compositions

[0169] Another embodiment described herein relates to a pharmaceutical composition comprising a compound of Formula I and/or a compound described herein, and a physiologically acceptable carrier, diluent,. or excipient, or a combination thereof. In some embodiments, a pharmaceutical composition comprises a compound of Formula (I) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, provided that when R ₂ and R _2a are taken together, along with the nitrogen atom to which they are attached, form a substituted heteroalicyclyl, wherein the substituted heteroalicyclyl is

substituted with n-butyl at the para-position, then B cannot be selected from the group consisting of methyl, -C(=O)Ri, and -CH2OH, wherein R] is hydrogen or methyl; or A cannot be methyl. In other embodiments, a pharmaceutical composition comprises a compound of Formula (I) or a solvate, a polymorph, a metabolite, or a pharmaceutically acceptable salt or prodrug thereof, provided that -when R ₂ and R _2a are taken together, along with the nitrogen atom to which they are attached, form a substituted heteroalicyclyl, wherein

the substituted heteroalicyclyl is substituted with an alkyl, such as n-butyl, then A, R ₃ , R3a, R3b, and R ₃₀ cannot all be hydrogen.

[0170] The term "pharmaceutical composition" refers to a mixture of a compound disclosed herein with other chemical components, such as diluents or carriers. The pharmaceutical composition facilitates administration of the compound to an organism. Multiple techniques of administering a compound exist in the art including, but not limited to, oral, intramuscular, intraocular, intranasal, intravenous, injection, aerosol, parenteral, and topical administration. Pharmaceutical compositions can also be obtained by reacting compounds with inorganic or organic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, p- toluenesulfonic acid, salicylic acid and the like. Pharmaceutical compositions will generally be tailored to the specific intended route of administration.

[0171] The term "physiologically acceptable" defines a carrier or diluent that does not abrogate the biological activity and properties of the compound.

[0172] The pharmaceutical compositions described herein can be administered to a human patient per se, or in pharmaceutical compositions where they are mixed with other active ingredients, as in combination therapy, or suitable carriers or excipient(s). Techniques for formulation and administration of the compounds of the instant application may be found in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, 18th edition, 1990, which is hereby incorporated by reference in its entirety.

[0173] Suitable routes of administration may, for example, include oral, rectal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intravenous, intramedullary injections, as well as intrathecal, direct intraventricular, intraperitoneal, intranasal, intraocular injections or as an aerosol inhalant.

[0174] Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into the area of pain or inflammation, often in a depot or sustained release formulation. Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with a tissue-specific antibody. The liposomes will be targeted to and taken up selectively by the the targeted organ or tissue.

[0175] The pharmaceutical compositions disclosed herein may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving,

granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tableting processes.

[01761 Pharmaceutical compositions for use in accordance with the present disclosure thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active compounds into preparations, which can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen. Any of the well-known techniques, carriers, and excipients may be used as suitable and as understood in the art; e.g., as disclosed in Remington's Pharmaceutical Sciences, cited above.

[0177] For injection, the agents disclosed herein may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological saline buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

[0178] For oral administration, the compounds can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the compounds disclosed herein to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated. Pharmaceutical preparations for oral use can be obtained by mixing one or more solid excipient with pharmaceutical combination disclosed herein, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

[0179] Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc,

polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

[0180] Pharmaceutical preparations, which can be used orally, include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for such administration.

[0181] For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.

[0182] For administration by inhalation, the compounds for use according to the present disclosure are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable propellant, e g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g , gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

[0183] The compounds may be formulated for parenteral administration by injection, e.g , by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g , in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.

[0184] Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the

active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances, which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents, which increase the solubility of the compounds to allow for the preparation of highly, concentrated solutions.

[0185] Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

[0186] The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.

[0187] In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

[0188] A pharmaceutical carrier for the hydrophobic compounds disclosed herein is a co-solvent system comprising benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. A common co-solvent system used is the VPD co-solvent system, which is a solution of 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant Polysorbate 80™, and 65% w/v polyethylene glycol 300, made up to volume in absolute ethanol. Naturally, the proportions of a co-solvent system may be varied considerably without destroying its solubility and toxicity characteristics. Furthermore, the identity of the co-solvent components may be varied: for example, other low-toxicity nonpolar surfactants may be used instead of Polysorbate 80™; the fraction size of polyethylene glycol may be varied; and other biocompatible polymers may replace polyethylene glycol, e.g., polyvinyl pyrrolidone. Alternatively, other delivery systems for hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are

well known examples of delivery vehicles or carriers for hydrophobic drugs. Certain organic solvents such as dimethyl sulfoxide also may be employed, although usually at the cost of greater toxicity. Additionally, the compounds may be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various sustained-release materials have been established and are well known by those skilled in the art. Sustained-release capsules may, depending on their chemical nature, release the compounds for a few weeks up to over 100 days. Depending on the chemical nature and the biological stability of the therapeutic reagent, additional strategies for protein stabilization may be employed.

[0189] Many of the compounds used in the pharmaceutical combinations disclosed herein may be provided as salts with pharmaceutically compatible counterions. Pharmaceutically compatible salts may be formed with many acids, including but not limited to hydrochloric, sulfuric, acetic, lactic, tartaric, malic, succinic, etc. Salts tend to be more soluble in aqueous or other protonic solvents than are the corresponding free acids or base forms.

[0190] Pharmaceutical compositions suitable for use in the methods disclosed herein include compositions where the active ingredients are contained in an amount effective to achieve its intended purpose. More specifically, a therapeutically effective amount means an amount of compound effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.

[0191] The exact formulation, route of administration and dosage for the pharmaceutical compositions disclosed herein can be chosen by the individual physician in view of the patient's condition. (See e.g., Fingl et al. 1975, in "The Pharmacological Basis of Therapeutics", Chapter 1, which is hereby incorporated by reference in its entirety). Typically, the dose range of the composition administered to the patient can be from about 0.5 to 1000 mg/kg of the patient's body weight, or 1 to 500 mg/kg, or 10 to 500 mg/kg, or 50 to 100 mg/kg of the patient's body weight. The dosage may be a single one or a series of two or more given in the course of one or more days, as is needed by the patient. Where no

human dosage is established, a suitable human dosage can be inferred from EDs ₀ or IDso values, or other appropriate values derived from in vitro or in vivo studies, as qualified by toxicity studies and efficacy studies in animals.

[0192] Although the exact dosage will be determined on a drug-by-drug basis, in most cases, some generalizations regarding the dosage can be made. The daily dosage regimen for an adult human patient may be, for example, an oral dose of between 0.1 mg and 500 mg of each ingredient, preferably between 1 mg and 250 mg, e.g. 5 to 200 mg or an intravenous, subcutaneous, or intramuscular dose of each ingredient between 0.01 mg and 100 mg, preferably between 0.1 mg and 60 mg, e.g. 1 to 40 mg of each ingredient of the pharmaceutical compositions disclosed herein or a pharmaceutically acceptable salt thereof calculated as the free base, the composition being administered 1 to 4 times per day. Alternatively the compositions disclosed herein may be administered by continuous intravenous infusion, preferably at a dose of each ingredient up to 400 mg per day. Thus, the total daily dosage by oral administration of each ingredient will typically be in the range 1 to 2000 mg and the total daily dosage by parenteral administration will typically be in the range 0.1 to 400 mg. In some embodiments, the compounds will be administered for a period of continuous therapy, for example for a week or more, or for months or years.

[0193] Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety, which are sufficient to maintain the modulating effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations.

[0194] Dosage intervals can also be determined using MEC value. Compositions should be administered using a regimen, which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%.

[0195] In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration.

[0196] The amount of composition administered will, of course, be dependent on the subject being treated, on the subject's weight, the severity of the affliction, the manner of administration and the judgment of the prescribing physician.

[0197] The compositions may, if desired, be presented in a pack or dispenser device, which may contain one or more unit dosage forms containing the active ingredient. The pack may for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, may be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. Compositions comprising a compound disclosed herein formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.

[0198] It will be understood by those of skill in the art that numerous and various modifications can be made without departing from the spirit of the present disclosure. Therefore, it should be clearly understood that the forms disclosed herein are illustrative only and are not intended to limit the scope of the present disclosure.

EXAMPLES

[0199] Embodiments of the present invention are disclosed in further detail in the following examples, which are not in any way intended to limit the scope of the invention.

General analytical LC-MS procedure

[0200] Procedure 1 (API): The analysis was performed on a combined prep/analytical Waters/Micromass system consisting of a ZMD single quadropole mass spectrometer equipped with electro-spray ionization interface. The HPLC system consisted of a Waters 600 gradient pump with on-line degassing, a 2700 sample manager and a 996 PDA detector.

[0201] Separation was performed on an X-Terra MS C 18, 5 μm 4.6x50mm column. Buffer A: 1OmM ammonium acetate in water, buffer B: 1OmM ammonium acetate in acetonitrile/water 95/5. A gradient was run from 30%B to 100%B in 10 min, dwelling at 100%B for 1 min, and re-equilibrating for 6 min. The system was operated at 1 ml/min.

[0202] Procedure 2 (AP2): The analysis was performed on a combined prep/analytical Waters/Micromass system consisting of a ZMD single quadropole mass spectrometer equipped with electro-spray ionization interface. The HPLC system consisted of a Waters 600 gradient pump with on-line degassing, a 2700 sample manager and a 996 PDA detector.

[0203] Separation was performed on an X-Terra MS C 18, 5 μm 4.6x50mm column. Buffer A: 1OmM ammonium acetate in water, buffer B: 1OmM ammonium acetate in acetonitrile/water 95/5. A gradient was run from 30%B to 100%B in 7 min, dwelling at 100%B for 1 min, and re-equilibrating for 5.5 min. The system was operated at 1 ml/min.

Analytical HPLC/MS, Ammonium Acetate TAP)

[0204] System: Waters/Micromass ZQ2000 LC/MS system consisting of a ZQ single quadropole mass spectrometer equipped with an electrospray ionization interface, and a Waters Alliance HT with a 2795 Separation Module and 996 Photodiode Array Detector.

[0205] Column: Reversed phase column (Waters Xterra® MS Cjβ 3.5μm, 30x4.6mm ID) with a guard column cartridge system.

[0206] Mobile Phase: A: 1OmM aqueous Ammonium Acetate; B: 1OmM aqueous Ammonium Acetate Acetonitrile/Water (95:5).

[0207] Program: 10 min. gradient program starting at 30%B (initial hold for 0.5 min.), over 5 min. to 100%B, hold for 1.5 min., over 0.5 min. to 30%B, hold for 2.5 min. The flow rate was 1 mL/min.

Preparative HPLC/MS, Ammonium Acetate (PP)

[0208] System: Waters/Micromass LC/ZMD Autopurification system consisting of a ZMD single quadropole mass spectrometer equipped with an electrospray ionization interface, and a Waters 600E Gradient Pump with in-line degassing, 2700 Sample Manager and 996 Photodiode Array Detector.

[0209] Column: Reversed phase column (Waters Xterra® Prep MS Cj s 5μm, 19x100mm).

[0210] Mobile Phase: A: 1OmM aqueous Ammonium Acetate; B: 1OmM aqueous Ammonium Acetate Acetonitrile/Water (95:5).

[0211] Program: 12 min. gradient program starting at 30%B (initial hold for 2.5 min.), over 8.5 min. to 100%B, over 0.5 min. to 30%B ₅ hold for 0.5 min. The flow rate was 17 mL/min.

Typical procedure 1 (See Scheme 1) (TPl): 1 -f 1 -O-chloropropyiyiH-indol-3-yli-ethanone

[0212] 3-Acetylindole (795 mg, 5 mmol), cesium carbonate (3.25 g, 10 mmol) and l-chloro-3-iodopropane (3.06 g, 15 mmol) were weighed into a MW vial and dry MeCN (15 mL) was added. The vial was capped and heated in the MW at 100 ⁰ C for 25 min. The reaction was filtrated and concentrated onto celite and purified by flash chromatography 0-30 % EtOAc in heptane. Yield: 971 mg (83%).

(0213] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40-8.37 (m, IH), 7.75 (s, IH), 7.37-7.28 (m, 3H) ₅ 4.36 (t, J = 6.0 Hz, 2H), 3.46 (t, J = 6.0 Hz, 2H) ₅ 2.51 (S ₅ 3H), 2.30 (pentet, J= 6.0 Hz ₅ 2H).

Typical procedure 2 (See Scheme 1) (TP2): l-(3-chloropropyl)-7-isopropoxy-lH-indole

[0214] 7-isopropoxy-lH-indole_(736 mg, 4.2 mmol), cesium carbonate (2.73 g, 8.4 mmol) and l-chloro-3-iodopropane (2.57 g, 12.6 mmol) were weighed into a vial and dry

MeCN (20 mL) was added. The vial was sealed and heated on a shaker at 50 ⁰ C for 24 h. The reaction was filtrated and concentrated onto celite and purified by flash chromatography 0-20 % EtOAc in heptane. Yield: 750 mg (71%).

[0215] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.2 (d, J = 7.8 Hz, 1 H), 7.04 (d, J = 3.1 Hz, 1 H), 6.99 (t, J= 7.8 Hz, 1 H) ₅ 6.62 (d, J= 7.8 Hz, 1 H) ₅ 6.43 (d, J= 3.1 Hz, 1 H), 4.80 - 4.73 (m, 1 H), 4.58 - 4.49 (m, 2H), 3.49 - 3.46 (m, 2H), 2.37 - 2.35 (m, 2H), 1.45 (d, J = 5.8 Hz, 6H).

Typical procedure 3 (See Scheme 2) (TP3):

1 -(7-bromo-l -(3-chloroproρyO-l H-indol-3-yDethanone

[0216] To a solution of 7-bromo-l //-indole (442 mg, 2.25 mmol) in dry CH ₂ Cl ₂ (10 mL) at 0 ⁰ C was added Et ₂ AlCl (3.4 mL, 1.0 M, 3.4 mmol) dropwise. The mixture was stirred at 0 ⁰ C for 25 min. A solution of AcCl (0.24 mL, 3.36 mmol) in CH ₂ Cl ₂ (5 mL) was added dropwise and the mixture was stirred at 0 ⁰ C until TLC showed complete conversion of the indole (1-3 h). Saturated aqueous NaHCO ₃ (10 mL) was added slowly and the mixture was allowed to reach room temperature. The mixture was diluted with CH ₂ Cb (60 mL) and the mixture was cautiously acidified to pH 4-5 with 2 M HCl (approx. 10 mL) to facilitate phase separation. The aqueous layer was extracted with CH ₂ Cl ₂ (2x 10 mL) and the combined organic layers where washed with saturated aqueous NaHCθ ₃ and evaporated to dryness to give the acetylated compound (496 mg, 93%). This acetyl ated crude product was dissolved in CH ₃ CN (10 mL). To this solution was added Cs ₂ CO ₃ (1.55 g, 4.76 mmol) and 1 - chloro-3-iodopropane (0.70 mL, 6.52 mmol) and the mixture was stirred at 50 ⁰ C overnight. The suspension was diluted with CH ₂ Cl ₂ (70 mL), filtered and adsorbed onto celite. After purification by flash chromatography (heptanes — > heptanes: EtOAc 3:2) the title product was obtained (61 1 mg, 86% over two steps.

[0217] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.41 (dd, J= 8.0, 1.1 Hz ₉ IH), 7.75 (s, IH), 7.44 (dd, J= 7.7, 1.1 Hz, IH), 7.12-7.08 (m, IH), 4.73 (t, J= 6.7 Hz, 2H), 3.50-3.47 (m, 2H), 2.50 (s, 3H), 2.39-2.33 (m, 2H).

[0218] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 192.5, 137.7, 132.8, 129.7, 128.7, 123.7, 122.1, 1 16.5, 103.5, 45.8, 41.3, 34.1 , 27.5.

Typical procedure (See Scheme 3) (TP4): N-(3-methylbenzyl)-lH-indole-3-carboxamide

[0219] Indole-3-carboxylic acid (644 mg, 4 mmol), 1-hydroxybenzotriazole (810 mg, 6 mmol), EDCI (1.15 g, 6 mmol), TEA (1.82 g, 18 mmol) and 3-methylbenzylamine (485 mg, 4 mmol) were weighed into a MW vial and dry MeCN (10 mL) was added. The vial was capped and heated in the MW at 140 °C for 15 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated in vacuo. The product was purified by recrystalization from MeOH. Yield: 41 1 mg (39%).

[0220] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.67 (bs, IH), 7.78 (d, J = 2.8 Hz ₃ IH), 7.48 (d, J= 8.0 Hz, IH), 7.25-7.13 (m, 6H), 6.70 (d, J= 8.0 Hz, IH), 6.23 (bt, IH), 4.68 (d, J = 5.6 Hz, 2H), 2.35 (s, 3H).

Typical procedure 5 (See Scheme 4 ^* ) ( ^" TP5):

^-(S-chloropropyD-N-O^-dichlorobenzvπ-y-methoxy-lH-indol e-S-carboxamide

[0221] To a stirring suspension Of MgI ₂ (706 mg, 2,54 mmol) in DCE (4 mL) was added l ,2-dichloro-4-(isocyanatomethyl)benzene (0.39 mL, 2.65 mmol) and l -(3- chloropropyl)-7-methoxy-lH-indole (567 mg, 2.53 mmol). The mixture was stirred at 80 ⁰ C for 2 h at which point full conversion was observed by TLC (prolonged stirring at room temperature also led to full conversion). The mixture was diluted with EtOAc (200 mL) and the organic layer was washed with saturated aqueous NaHCO3, H ₂ O, 10% aqueous Na2SO3, brine, dried over Na ₂ SO ₄ and evaporated to dryness. After washing the resulting crystals with diethyl ether (3x 10 mL) the title compound was obtained as pinkish crystals (788 mg, 73%) which was used without further purification. 0-15% of the corresponding alkyl iodide was occasionally observed in these reactions, in particular when the reaction was performed at 80 ⁰ C.

[0222] ¹ H NMR (400 MHz, dmso-d ₆ ) δ 8.48-8.45 (m, IH), 7.93 (s, IH), 7.75 (dd, J = 8.1, 0.8 Hz, IH), 7.59-7.56 (m, 2H), 7.33 (dd, J = 8.3, 2.0 Hz, IH), 7.04 (t, J = 7.9 Hz, IH) ₅ 6.75 (d, J= 7.5 Hz, IH), 4.51-4.43 (m, 4H), 3.90 (s, 3H), 3.60 (t, J= 6.3 Hz, 2H), 2.28- 2.18 (m, 2H).

[0223] ¹³ C NMR (IOO MHZ, dmso-d ₆ ) δ 164.1 , 146.9, 141.6, 131.8, 130.6, 130.3, 129.1, 129.0, 128.8, 127.5, 125.2, 121.5, 1 13.8, 109.6, 103.5, 55.4, 46.6, 42.2, 40.9, 34.0.

Typical procedure 6 (See Scheme 5) fTPό): 7-isopropoxy- 1 H-indole

^" ' [0224] 7-hydrozyindol (1.00 g, 7.5 mmol) and resin bound triphenylphosphine (4.25 g, 13 mmol, 3 mmol/g) was taken up in THF (30 mL) and cooled to 0 ⁰ C ₅ before drop wise addition of diisopropylazodicarboxylate (787 mg, 3.9 mmol). After 40 min at 0 ⁰ C isopropanol (1.80 g, 30 mmol) in THF (15 mL) was added slowly. The reaction was left for further 2 h at 0 ⁰ C, then the cooling was removed and the reaction left at room temperature over night. The reaction mixture was filtered and concentrated onto celite, then purified by flash chromatography 0-20% EtOAc in heptane. Yield: 736 mg (56 %).

[02251 ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.26 (dd, J= 0.8 and 7.4 Hz ₅ 1 H), 7.17 (t, J = 2.8 Hz ₅ 1 H), 7.06 (dt, J= 0.8 and 7.4 Hz, 1 H), 6.60 (d, J= 7.4 Hz, 1 H), 6.54 (dt, J = 0.8 and 2.8 Hz ₅ 1 H), 4.76 (hept, J= 6.2 Hz, 1 H), 1.44 (d, J= 6.2 Hz, 6 H).

Typical procedure 7 (TP7): 3α-(4-chlorophenoxyV8-azabicvclor3.2.1 loctane

[0226] 4-Chlorophenol (395 mg, 3 mmol) and resin bound triphenylphosphine (1.20 g, 3.75 mmol, 3 mmol/g) was taken up in THF (10 mL) and cooled to 0 ⁰ C, before drop wise addition of diisopropylazodicarboxylate (787 mg, 3.9 mmol). After 40 min at 0 ⁰ C tert- butyl 3β-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate (500 mg, 2.2 mmol) in THF (5 mL) was added slowly. The reaction was continued for 2 h at 0 °C, then the cooling was removed and the reaction left at room temperature over night. The reaction mixture was filtered and concentrated onto celite, then purified by flash chromatography 0-30% EtOAc in heptane. The product was taken up in DCM (5 mL), TFA (5 mL) was added and the reaction

mixture left stirring for 1 h and concentrated in vacuo. The product was taken up in EtOAc, then washed with NaOH (2 N), dried over sodium sulphate, filtered and concentrated in vacuo. Yield: 370 mg (71 % over two steps).

[0227] ¹ H NMR (400 MHz, CD ₃ OD) δ: 7.29-7.26 (m, 2H) ₅ 6.90-6.88 (m, 2H), 4.67 (bt, J= 4.4 Hz, IH), 3.92-3.91 (m, 2H), 2.39-2.00 (m, 7H).

102281 ¹³ C NMR (100 MHz, CD ₃ OD) δ: 159.7, 133.5, 129.9, 120.8, 72.4, 58.0, 37.0, 30.2.

Typical procedure 8 (See Scheme 6) (TP8): l-(7-Methoxy-lH-indol-3-yDethanone

{0229] MeMgBr (3 ml, 3M in ether, 9 mmol) was added to 7-methoxy-lH-indole dissolved in dry Cη ₂ CI ₂ (6 ml) at 0-5 ⁰ C. The resulting red solution was stirred for 1 h at room temperature. Freshly distilled acetyl chloride (353 mg, 4.5 mmol) was then added at 0-5 ⁰ C and the resulting brown solution was stirred for 1 h at room temperature. Aqueous HCl (2M) was added to the reaction mixture and the organic phase was separated. The aqueous phase was extracted with CH ₂ Cl ₂ and the combined organic phases were washed with water, brine and dried with Na ₂ SO^ The filtrate was concentrated at reduced pressure and the crude product was purified by crystallization (heptane/ethyl acetate 3:1), which gave 345 mg (70%) of the title compound as brown crystals.

[0230] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.80 (br s, IH), 7.93 (d, IH, J = 8.0 Hz), 7.81 (d, IH, J= 2.9 Hz) ₅ 7,20 (t, IH ₅ J= 8 Hz) ₃ 6.73 (d, IH J= 7.9 Hz), 3.96 (s, 3H) ₅ 2.55 (s, 3H).

Typical procedure 9 ('See Scheme 7) (TP9): OS'.45^-2-r2-( ^' 4-fluorophenoxy')ethylV2.5-diazabicvclor2.2.21octane

[0231] A 4 mL disposable vial was charged with (l S,4S)-/e/-/-butyl 2,5- diazabicyclo[2.2.2]octane-2-carboxylate hydrochloride (252 mg, 1.02 mmol), l-(2- bromoethoxy)-4-fluorobenzene (362 mg, 1.65 mmol), Cs ₂ CO ₃ (576 mg, 1.77 mmol) and CH ₃ CN (2 mL). The mixture was sealed and stirred at 60 ⁰ C overnight. The suspension was disluted with CH ₂ Cl ₂ (25 mL), filtered and evaporated to dryness. The resulting crude product was dissolved in CH ₂ Cl ₂ (10 mL) and TFA (5 mL) was cautiously added. After stirring at room temperature for 3 h the mixture was evaporated to dryness. The crude product was dissolved in a minimal amount of MeOH and purified by solid phase extraction using a SCX cartridge eluding with NH ₃ (MeOH) to give the title compound (191 mg, 75% over two steps).

[0232J ¹ H NMR (400 MHz, CDCl ₃ ) δ 6.98-6.93 (m, 2H), 6.85-6.82 (m, 2H), 4.04-4.00 (m, 2H), 3.44-3.41 (m, IH) ₅ 3.10-3.08 (m, IH), 3.00-2.97 (m, 4H), 2.73-2.70 (m, 3H), 2.10-2.02 (m, IH), 1.95-1.88 (m, IH) ₅ 1.80-1.70 (m, 2H).

[0233] ¹³ C NMR (I OO MHZ, CDCl ₃ ) δ 157.5 (d, J= 237 Hz), 155.2, 1 16.0 (d, J = 29 Hz), 1 15.9 (d, J= 1.4 Hz), 67.9, 57.8, 55.5, 50.2, 45.6, 45.0, 25.8, 24.2.

Typical procedure 10 (See Scheme 8) (TPl O):

Tert-butyl flR.5S>3 α -(2-oxo-2-phenylethylV8-azabicvclor3.2.noctane-8-carboxylate

[0234] To a solution of KlR,5S)-8-(tert-butoxycarbonyI)-8-azabicyc]o[3.2.1]oct- 3 α -yl]acetic acid (807 mg, 3 mmol) in THF (10 mL) was added CDMT (624 mg, 3.6 mmol) and NMM (0.99 mL, 9 mmol). A white precipitate was formed during stirring, for 1 hour,

then N,0-dimethylhydroxylamine hydrochloride (291 mg, 3 mmol) was added and the reaction mixture left stirring for 16 h, quenched with water (20 mL) and extracted with ether. The ether phase was washed with sat. aq. Na ₂ Cθ ₃ and HCl (1 N), then dried over Na ₂ SO ₄ and concentrated in vacuo. Yield: 894 mg (95%).

[0235J The crude product was taken up in THF and cooled to 0 ⁰ C, then phenyl grignard (3 mL, 2 M, 6 mmol) was added and the ice bath removed. After 1 h at rt the reaction mixture was quenched with sat. aq. NH ₄ Cl. The product was extracted with EtOAc and the organic phase was washed with Na ₂ CO ₃ , then HCl (1 N), dried over Na ₂ Sθ4 and concentrated in vacuo. Crude yield: 847 mg (90 %). UV/MS: 84/62.

(0236] ¹ H NMR (CDCl ₃ ) δ: 7.93-7.90 (m, 2H), 7.58-7.55 (m, IH), 7.47-7.43 (m, 2H), 4.24-4.12 (m, 2H) ₃ 3.12-3.11 (m, 2H), 2.04-2.00 (m, IH), 1.73-1.71 (m, 2H), 1.44 (s, 9H) ₅ 1.30-1.26 (m, 4H) ₅ 0.89-0.86 (m, 2H).

Typical procedure 1 1 (See Scheme 9) (TPl 1):

(1 R,5SV3α-f2-phenvIethyl)-8-azabicvclor3.2, 1 loctane

[0237] Tert-butyl (lR,5S)-3 α -(2-oxo-2-phenylethyl>8-azabicyclo[3.2.1]octane- 8-carboxylate (847 mg, 2.5 mmol) and KOH (540 mg, 9.6 mmol) was taken up in diethyleneglycol (5 mL) then hydrazine monohydrate (401 μL, 8.3 mmol) was added and the RM was heated to 140 ⁰ C on an oil bath for 16 h. Cooled on an ice bath and quenched with HCl (2 N). Extracted with EtOAc, then dried over Na ₂ SO ₄ and concentrated in vacuo onto celite. The crude product was purified by flash chromatography 0-20 % EtOAc in heptane. Yield: 234 mg (30 %). The isolated product was taken up in a mixture of TFA (2 mL) and DCM (2 mL) and stirred for 1 h at rt,concentrated in vacuo, then taken up in EtOAc, washed with NaOH (2 N), dried over Na ₂ SO ₄ and concentrated in vacuo. Yield: 160 mg (96 %).

[0238] ¹ H NMR (400 MHZ, CDCl ₃ ): δ 7.30-7.14 (m, 5H) ₅ 3.89-3.83 (m, 2H), 2.63-2.59 (m, 2H), 2.33-2.26 (m, 2H), 2.13-2.10 (m, 2H) ₅ 1.91-3.68 (m, 5H), 1.59-1.55 (m, 2H).

[0239] ¹³ C NMR (100 MHz, CDCl ₃ ) - major isomer: δ 142.0, 128.7, 128.5, 126.2, 54.3, 39.7, 35.0, 33.6, 27.5, 27.4.

Typical procedure 12 fSee Scheme 10) CTP 12):

1 -d -(3-(4-(4-Fluorophenoxy)piperidin-l -yl)propyIV7-methoxy-l //-indol-3-yl)ethanone oxalate C658b

[0240] 4-(4-fluorophenoxy)piperidine hydrochloride (163 mg, 0.70 mmol) was added to l-(l-(3-Chloropropyl)-7-methoxy-lH-indol-3-yl)ethanone (93 mg, 0.35 mmol), triethylamine (99 μl, 0.70 mmol) and NaI (cat) in dry DMF (4 ml). The reaction mixture was shaken at 80 ⁰ C for 15 h and at 120 ⁰ C for 1 h. Ethyl acetate and water was then added to the reaction mixture and the organic phase was washed repeatedly with water and finally with brine. Celite was added to the filtrate and the volatile material was removed at reduced pressure. The crude product on celite was purified by column chromatography (heptane/ethyl acetate 1 :1 to 100% ethyl acetate and then ethyl acetate/methanol 9:1 to 4:1), which gave 90 mg (61%) of l-(l-(3-(4-(4-fluorophenoxy)piperidin-l-yl)propyl)-7-methoxy -lH-indol-3- yl)ethanone compound as a clear oil.

[0241] ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.97 (d, IH, J= 8.0 Hz), 7.70 (s, IH), 7.17 (t, IH, J = 8 Hz), 6.95 (m, 2H) ₃ 6.84 (m, 2H), 6.71 (d, IH J = 7.8 Hz), 4.47 (t, 2H, J= 6.4 Hz), 4.24 (m, IH), 3.94 (s, 3H), 2.73 (m, IH), 2.49 (s, 3H), 2.32 (m, 4H), 2.05 (m, 4H) _} 1.84 (m, 2H). Oxalic acid (1.1 eq) dissolved in acetone (1 ml) was added to the clear oil dissolved in acetone (1 ml). The precipitant was filtered off and dried to yield 90 mg of the title compound as white crystals. MS (ES ⁺ , M+l) = 425.

Typical procedure 13 (See Scheme 11) CTP 13 ^s ): N-methoxy-N-methyl- 1 H-indole-3-carboxamide

[0242] To a solution of lH-indole-3-carboxylic acid (650 mg, 4 mmol) in DCM (10 mL) in a MW vial was added N,O-dimethylhydroxylamine hydrochloride (423 mg, 4.4 mmol), PPh ₃ (SOO mg, 8 mmol), CCl ₄ (4 mL) and MMP (0.98 mL, 8.9 mmol). The vial was capped and heated in the MW at 100 ⁰ C for 12 min, the reaction mixture was subsequently stirred at it over night. The resulting mixture was filtered, diluted with DCMj washedwith HCl (0.5 N) and sat. aq. Na ₂ CO ₃ , then dried over Na ₂ SO ₄ and concentrated in vacuo. Yield: 2l9 mg (27%).

[0243] ¹ H NMR (400 MHZ, CDCl ₃ ): δ 8.85 (bs, IH), 8.4 (d, J= 7.6 Hz ₅ IH), 7.97 (d, J= 2.1 Hz, IH), 7.40.7.22 (m, 3H), 3.71 (s, 3H), 3.42 (s, 3H).

1 -( 1 H-pyrrol o [2 , 3 -b)pγ ri din-3 -vDethanone

[0244] To a suspension Of AlCl ₃ (4.91 g, 36.8 mmol) in CH ₂ Cl ₂ (100 mL) at rt was added lH-pyrrolo[2 _} 3-6]pyridine (899 mg, 7.61 mmol). After 60 min AcCl (2.7 mL, 37.8 mmol) was added dropwise and the mixture was stirred overnight. The reaction was quenched by carefull addition of MeOH (35 mL) and evaporated to dryness. Saturated aqueous NaHCO ₃ (150 mL) and EtOAc (100 mL) were added to the residue followed by vigorous stirring. The aqueous layer was extracted with EtOAc (2x 100 mL), and the combined organic layers were dried over Na ₂ SO ₄ and evaporated to dryness to give the title compound as colorless crystals (803 mg, 66%).

[0245] ¹ H NMR (400 MHz, CD ₃ OD) δ 8.70 (dd, J = 7.9, 1.6 Hz, IH), 8.37-8.35 (m, 2H), 7.37 (dd, J= 7.9, 5.0 Hz, I H), 2.58 (s, 3H).

7-methoxy-l//-indole-3-carbonitrile

[0246] To a solution of 7-methoxy-l//-indole-3-carboxylic acid (363 mg, 1.90 mmol) in DMF (10 mL) was added carbonyl diimidazole (382 mg, 2.36 mmol) in one portion. After stirring at room temperature for Ih 30 min 28% aqueous NH ₃ (0.50 mL, approx. 7 mmol) was added, and the mixture was left stirring overnight. After evaporation to dryness the remanens was taken up in EtOAc (200 mL) and the organic layer was washed with H ₂ O (2x 10 mL), saturated aqueous NaHCC> ₃ (10 mL), brine, dried over Na ₂ SO ₄ and evaporated to dryness to give the intermediate amide (527 mg). This amide was dissolved in a mixture of CH ₃ CN (15 mL) and H ₂ O (15 mL). The mixture was heated to 50 ⁰ C and Pd(OAc) ₂ (408 mg, 1.81 mmol) was added in portions over 24 h. The black reaction mixture was quenched with saturated aqueous NaHCO ₃ (25 mL) and the CH ₃ CN was removed by rotary evaporation. The remaining aqueous layer was extracted with EtOAc (3x 25 mL). The combined organic layers washed with brine, dried over Na ₂ SO ₄ and evaporated to dryness to give the pure title compound (134 mg, 41% overall yield.).

[0247] One peak GC-MS m/z (relative intensity) 172(100), 157(67), 129(60), 102(1 1).

1 -( 1 -(3-chloropropyl)- 1 H-pyrrolof 2,3-b ^~ |pyridin-3-ylV2,2,2-trifluoroethanone

[0248] Prepared according to TP2, see also Scheme 1, using 2,2,2-trifluoro-l- (lH-pyrrolo[2,3-b]pyridin-3-yl)ethanone (253 mg, 1.18 mmol), Cs ₂ CO ₃ (810 mg, 2.49 mmol) and l -chloro-3-iodopropane (0.40 mL, 3.7 mmol) in Cη ₃ CN (10 mL). Purification was by flash chromatography (heptanes — > heptanes.EtOAc 3:2) to give the title compound (241 mg, 70%).

[0249] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.59 (dd, J = 7.9, 1.6 Hz ₃ IH) ₃ 8.43 (dd, J = 4.7, 1.6 Hz, IH), 8.1 1 (d, J= 1.7 Hz, IH) ₃ 7.29 (dd, J= 7.9, 4.7 Hz, IH), 4.58-4.54 (m, 2H), 3.53-3.50 (m ₃ 2H) ₅ 2.46-2.39 (m, 2H).

[0250] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 174.9 (q, J = 35.4 Hz), 147.8, 145.6, 137.5 (q, J= 4.8 Hz), 130.9, 119.7, 119.4, 116.8 (q, J= 290.8 Hz), 108.0, 43.2, 41.3, 31.8.

l-(l-(3-chloroprbpyl ^' )-l//-pyrrolor2,3-b1pyridin-3-yl)ethanone

[0251] Prepared according to TP2, see also Scheme 1, by using 1-(1/J- pyrrolo[2,3-6]pyridin-3-yl)ethanone (492 mg, 3.07 mmol), Cs ₂ CO ₃ (1.53 g, 4.70 mmol), 1- chloro-3-iodopropane (0.90 mL, 8.4 mmol) in CH ₃ CN (15 mL) to give the title compound (338 mg, 47%).

[0252] ¹ H NMR (400 MHz, CDCl ₃ ) 6 8.51 (dd, J= 8.0, 1.6 Hz, IH) ₃ 8.29 (dd, J = 4.8, \.6 Hz ₃ IH), 7.82 (s, IH), 7.14 (dd, J = 8.0, 4.8 Hz, IH), 4.44-4.40 (m, 2H) ₅ 3.45-3.42 (m, 2H), 2.43 (s, 3H), 2.35-2.28 (m ₃ 2H).

[0253] ¹³ C NMR (100 MHz, CDCI ₃ ) δ 192.4, 147.6, 144.2, 134.5, 130.7, 1 18.5, 1 18.3, 1 15.2, 42.3, 41.4, 31.9, 26.9.

1 -(3-chloropropyiy 7-methoxy- 1 H-indole-3-carbonitrile

[0254] Prepared according to TP2, see also Scheme 1, by using 7-methoxy- 1 H- indole-3-carbonitrile (134 mg, 0.78 mmol), Cs ₂ CO ₃ (809 mg, 2.48 mmol), l-chloro-3- iodopropane (0.45 mL, 4.2 mmol) in CH ₃ CN (6 mL) to give the title compound (138 mg, 71%).

[0255] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ 7.51 (s, IH), 7.32-7.30 (m, IH), 7.18-7.14 (m, IH), 6.73-6.71 (m, IH) ₅ 4.57-4.54 (m, 2H), 3.94 (s, 3H) ₅ 3.45-3.42 (m, 2H), 2.31-2.25 (m, 2H).

[0256] 13 C NMR (100 MHz, CDCl ₃ ) δ 147.6, 135.7, 130.3, 124.7, 122.9, 1 15.6,

1 12.2, 104.3, 85.7, 55.4, 47.1, 41.3, 33.8.

l-Q-chloropropyiyN-D-methylbenzylMH-indole-S-carboxamide

[0257] Prepared according to TPl ₅ see also Scheme 1, using N-(3-methylbenzyl)- l//-indole-3-carboxamide (264 mg, 1 mmol), cesium carbonate (650 mg, 2 mmol) and 1- chIoro-3-iodopropane (612 mg, 3 mmol) in MeCN (4 mL). The product was purified by flash chromatography 0-30 % EtOAc in heptane. Yield; 280 mg (82%).

[0258] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.60 (s, IH) ₅ 7.54 (dd, J= 8.0 and 0.8 Hz, IH), 7.26-7.10 (m, 6H) ₅ 6.68 (d, J= 8.0 Hz, IH) ₅ 6.15 (bt, IH), 4.66 (d, J= 5.6 Hz, 2H) ₅ 4.56 (t, J= 6.6 Hz ₅ 2H), 3.47 (t, J= 6.6 Hz ₅ 2H), 2.35 (s, 3H), 2.29 (pentet, J= 6.6 Hz, 2H).

N-(3-chloro benzyl)- 1 H-indole-3-carboxamide

[0259] Prepared according to TP4, see also Scheme 3, using indole-3-carboxylic acid (644 mg, 4 mmol), 1 -hydroxybenzotriazole (810 mg, 6 mmol), EDCI (1.15 g, 6 mmol),

TEA (1.82 g, 18 mmol) and 3-chlorobenzylamine (566 mg, 4 mmol) in MeCN (10 mL). The product was purified by recrystalization from MeOH. Yield: 540 mg (48%).

[0260] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.58 (bs, IH), 7.96-7.94 (m, IH), 7.82 (d, J= 2.4 Hz, IH), 7.45-7.44 (m, IH), 7.39 (s, IH), 7.30-7.26 (m, 5H), 6.26 (bt, IH), 4.70 (d, J = 5.6 Hz ₅ 2H).

l-O-chloropropyD-N-O-chlorobenzyD-lH-indole-S-carboxamide

[0261] Prepared according to TP4, see also Scheme 3, using iV-(3-chlorobenzyl)- lH-indole-3-carboxamide (284 mg, 1 mmol), cesium carbonate (650 mg, 2 mmol) and 1- chloro-3-iodopropane (612 mg, 3 mmol) in MeCN (4 mL). The product was purified by flash chromatography 0-30 % EtOAc in heptane. Yield: 170 mg (48%).

[0262] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.98-7.96 (m, IH), 7.77-7.72 (m, IH), 7.44-7.24 (m, 7H), 6.28 (bt, IH), 4.68 (d, J= 6.0 Hz, 2H), 4.36 (t, J= 6.4 Hz, 2H), 3.47 (t, J = 6.4 Hz ₅ 2H), 2.30 (pentet, J= 6.4 Hz, 2H).

7-methoxy-N-f3-methylbenzyiyiH-indole-3-carboxamide

[0263] Prepared according to TP4, see also Scheme 3, using 7-methoxyindole-3- carboxylic acid (764 mg, 4 mmol), l-hydroxybenzotriazole (810 mg, 6 mmol), EDCI (1.15 g,

6 mmol)., TEA (1.82 g, 18 mmol) and 3-methylbenzylamine (485 mg, 4 mmol) in MeCN (10 mL). The product was purified by recrystalization from MeOH. Yield: 466 mg (40%).

[0264] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.81 - 7.79 (m, IH) ₃ 7.49 (d, J= 6.4 Hz, IH), 7.33 - 7.10 (m, 5H), 6.72 (d, J= 6.4 Hz, IH) ₅ 4.70 - 4.68 (m, 2H), 3.97 (s, 3H) ₅ 2.38 (s, 3H).

N-(3 -chlorobenzyl)-7-methoxy- 1 H-indole-3 -carboxamide

[0265] Prepared according to TP4, see also Scheme 3, from 7-methoxyindole-3- carboxylic acid (764 mg, 4 mmol) and 3-chlorobenzylamine (564 mg, 4 mmol) to yield the title compound. Yield: 478 mg (38%).

[0266] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.78 (d, J = 2.7 Hz, IH), 7.47 (d, J = 8.2 Hz ₅ IH), 7.28-7.20 (m, 4H), 7.16 (t, J= 8.2 Hz, IH), 6.70 (d, J= IA Hz, IH) ₅ 4.68 (d, J= 5.8 Hz ₅ 2H), 3.96 (s, 3H).

N-isobutyl-7-methoxy-lH-indole-3-carboxamide

[0267] Prepared according to TP4, see also Scheme 3, from 7-methoxyindole-3- carboxylic acid (764 mg, 4 mmol) and isobutyl amine (292mg, 4 mmol) to yield the title compound. Yield: 422 mg (43%).

[0268] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.77 (d, J = 2.7 Hz ₃ IH) ₅ 7.45 (d, J = 7.8

Hz, IH), 7.17 (t, J= 7.8 Hz, IH), 6.70 (d, J= 7.8 Hz, IH), 3.96 (s, 3H), 3.34 (t, J= 6.6 Hz, 2H), 1.95- 1.92 (m, 1 H), 1.02- 1.00 (m, 6H).

[0269] ¹³ C NMR (100 MHz ₃ CDCl ₃ ) δ: 163.5, 146.7, 127.7, 126.1, 122.4, 1 14.7, 1 12.3, 102.8, 102.3, 55.6, 47.1, 29.0, 20.5.

l-(3-chloropropyl)-7-methoxy-N-( ^' 3-methylben2yl ^' )-lH-indole-3-carboxamide

[0270] Prepared according to TP2, see also Scheme 1, using 7-methoxy-N-(3- methylbenzyl)-lH-indole-3-carboxamide (441 mg, 1.5 mmol), cesium carbonate (975 mg, 3 mmol) and l-chloro-3-iodopropane (918 mg, 4.5 mmol) in MeCN (10 mL) was added. Yield: 438 mg (78%).

[0271] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.60 (s, IH), 7.54 (dd, J= 0.8 and 7.8 Hz, IH), 7.26 -7.10 (m, 5H), 6.68 (d, J = 7.8 Hz, IH), 4.65 (d, J = 5.6 Hz, 2H), 4.56 (t, J = 6.6 Hz, 2H), 3.94 (s, 3H), 3.47 (t, J = 6.4 Hz, 2H), 2.35 (s, 3H), 2.31 - 2.27 (m, 2H).

[0272] 13 C NMR (100 MHz, CDCl ₃ ) δ: 173.1, 148.2, 139.2, 132.6, 128.8, 128.3,

127.8, 126.3, 125.0, 122.4, 1 13.1, 113.1, 111.8, 111.2, 103.5, 55.5, 47.2, 43.7, 41.9, 34.5, 34.4.

N-Q-chlorobenzyl)- 1 -(3-chloropropyl)-7-methoxy- 1 H-indole-3-carb ^' oxamide

[0273] Prepared according to TP2, see also Scheme 1, from N-(3-chlorobenzyl)- 7-methoxy-lH-indole-3-carboxamide (471 mg, 1.5 mmol) to yield the title compound. Yield: 418 mg (72%).

[0274] ¹ H-NMR (400 MHz ₅ CDCl ₃ ) δ: 7.61 (s, IH), 7.53 (d ₌ J= 8.2 Hz, IH) ₅ 7.28 - 7.24 (m, 4H) ₅ 7.14 (t ₅ J= 7.8 Hz, IH), 6.69 (d, J - 7.8 Hz ₅ IH) ₅ 4.66 (d, J= 5.8 Hz, 2H), 4.56 (t, J= 6.7 Hz, 2H), 3.95 (s ₅ 3H) ₅ 3.47 (t, J= 6.7 Hz, 2H), 2.29 (pent, J= 6.7 Hz, 2H).

[0275] ¹³ C-NMR (100 MHz, CDCl ₃ ) δ: 165.2, 147.9, 141.3, 132.7, 130.2, 128.3, 128.0, 127.8, 126.2, 126.1, 122.6, 113.2, 1 13.1, 1 1 1.0, 103.7, 76.7, 55.6, 47.2, 43.1, 41.9, 34.5.

l-O-chloropropyiyN-isobutyl^-methoxy-lH-indole-S-earboxam ide

[0276] Prepared according to TP2, see also Scheme 1, from N-isobutyl-7- methoxy-lH-indole-3-carboxamide (369 mg, 1.5 mmol) to yield the title compound. Yield: 342 mg (70%).

[0277] ¹ H-NMR (400 MHz, CDCl ₃ ) δ: 7.61 (s, IH), 7.55 (d, J= 7.8 Hz, IH), 7.14 (t, J= 7.8 Hz, IH), 6.69 (d, J = 7.8 Hz ₅ IH) ₅ 4.56 (t, J= 6.4 Hz, 2H), 3.95 (s, 3H), 3.47 (t, J = 5.8 Hz, 2H), 3.32 (t, J= 5.8 Hz, 2H), 2.30 - 2.27 (m, 2H) ₅ 1.93 (hept, J = 6.4 Hz, IH), 1.00 (d, J = 6.4 Hz, 6H).

l-(3-chloropropyl ^' )-7-isopropoxy-N-(3-methylbenzyl)-lH-indole-3-carboxamide

[0278] Prepared according to TP5 from l-(3-chloropropyl)-7-isopropoxy-lH- indole (251 mg, 1 mmol) and l-(isocyanatomethyl)-3-methylbenzene (154 mg, 1.05 mmol). The obtained solid was washed with MeOH. Yield 269 mg (67%).

[0279] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.59 it, J = 1.6 Hz, IH), 7.51 - 7.46 (m, IH), 7.26 - 7.17 (m, 3H), 7.11 - 7.06 (m, 2H), 6.66 (d, J = 7.8 Hz, IH), 4.75 (hept, J = 6.3 Hz, IH), 4.65 (d, J = 5.5 Hz, 2H), 4.57 (t, J = 6.1 Hz, 2H), 3.48 (t, J = 6.3 Hz, 2H), 2.30 (pent, J= 6.2 Hz, 2H), 1.56 (s, 3H), 1.42 (d, J= 5.5 Hz, 6H).

l-fS-chloropropylVN-Gλ-dichlorobenzvD^-isopropoxy-lH-ind ole-S-carboxamide

[0280] Prepared according to TP5, see also Scheme 4, from l-(3-chloropropyl)-7- isopropoxy-lH-indole (251 mg, 1 mmol) and l,2-dichloro-4-(isocyanatomethyl)benzene (212 mg, 1.05 mmol). The obtained solid was washed with MeOH. Yield 270 mg (61%).

[0281] ¹ H-NMR (400 MHz, CDCl ₃ ) δ: 7.64 - 7.60 (m, IH), 7.49 - 7.38 (m, 3H), 7.26 - 7.21 (m, IH), 7.11 - 7.09 (m, I H), 6.69 - 6.66 (m, IH), 4.76 - 4.49 (m, 4H), 3.49 - 3.46 (m, IH), 2.32 - 2.29 (m, 2H) ₃ 1.57 - 1.56 (m, 2H), 1.43 - 1.39 (m, 6H).

1 -(I -(3-chloropropylV7-methyl-lH-indol-3-yl)ethanone

[0282] Acetylation was carried out according to TP8, see also Scheme 6, using 7- methyl-1 //-indole (369 mg, 2.81 mmol), MeMgBr (2.8 mL, IM, 2.8 mmol) in CH ₂ Cl ₂ (6 mL). Subsequent alkylation of the crude product was carried out according to TPl using 3- iodo-1 -chloropropane (0.45 mL, 4.2 mmol) and Cs ₂ CO ₃ (1.19 g, 3.7 mmol) in a mixture of CH ₃ CN (3 mL) and DMF (2 mL) to give the title compound. Yield: 248 mg (35%).

[0283] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.31-8.29 (m, IH), 7.73 (s, IH) ₅ 7.19-7.15 (m, IH) ₅ 7.04-7.02 (m, IH), 4.57 (t, J = 6.7 Hz, 2H), 3.52-3.50 (m, 2H) ₃ 2.72 (s, 3H), 2.52 (s, 3H), 2.32-2.25 (m, 2H).

(l-( ^" 3-chloropropyl ^' )-7-methoxy-I//-indol-3-yl)('cvclopropyl)methanone

[0284] Prepared according to TP3, see also Scheme 2, by using 7-methoxy-lH- indole (365 mg, 2.48 mrnol), Et ₂ AlCl (3.5 ml, 1.0 M, 3.5 mmol), cyclopropanecarbony! chloride (0.31 mL, 3.4 mmol) in CH ₂ Cl ₂ (6 mL) and Cs ₂ CO ₃ (2.38 g, 7.2 mmol), I-chloro-3- iodopropane (0.70 mL, 6.52 mmol) in CH»CN (10 mL) to give the title compound (401 mg, 55% over two steps).

[0285] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (dd, J= 8.1 , 0.9 Hz, IH), 7.79 (s, IH), 7.13-7.12 (m, IH), 6.70 (d, J= 7.8 Hz, IH), 4.56 (t, J = 6.5 Hz, 2H), 3.92 (s, 3H), 3.48-3.45 (m, 2H), 2.44-2.38 (m, IH), 2.33-2.27 (m, 2H) ₅ 1.23-1.20 (m, 2H), 0.93-0.89 (m, 2H). fO286] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 194.7, 146.9, 135.4, 128.7, 125.8, 123.0, 117.1, 115.0, 104.0, 55.1, 47.0, 41.6, 33.8, 17.9, 9.6.

l-tT-chloro-l-O-chloropropyP-lH-indol-3-yQethanone

[0287] Prepared according to TP3, see also Scheme 2, by using 7-chloro-lH- indole (310 mg, 2.04 mmol), Et ₂ AlCl (3.0 mL, 1.0 M, 3.0 mmol), AcCl (0.21 mL, 2.9 mmol) in CH ₂ Cl ₂ (9 mL) and Cs ₂ CO ₃ (1.32 g, 4.1 mmol), l -chloro-3-iodopropane (0.65 mL, 6.1 mmol) in CH ₃ CN (10 mL) to give the title compound (438 mg, 79% over two steps).

[0288] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.32 (dd, J= 7.9, 1.2 Hz, IH), 7.69 (s, IH), 7.21-7.11 (m, 2H) ₅ 4.63 (t, J= 6.7 Hz, 2H), 3.45 (t, J= 5.9 Hz, 2H), 2.46 (s, 3H), 2.34-2.28 (m, 2H).

π-(3-chloropropyiy7-methoxy--lH-indol-3-yl)fphenyl)metha none

[0289] Prepared according to TP3, see also Scheme 2, by using 7-methoxy-l//- indole (318 mg, 2.16 mmol), Et ₂ AlCl (3.2 mL, 1.0 M, 3.2 mmol), benzoyl chloride (0.39 mL, 3.4 mmol) in CH ₂ Cl ₂ (6 mL) and Cs ₂ CO ₃ (1.67 g, 5.1 mmol), l-chIoro-3-iodopropane (0.70 mLj 6.5 mmol) in CH ₃ CN (10 mL) to give the title compound (430 mg, 61% over two steps). ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (dd, J= 8.1, 0.9 Hz, IH), 7.82-7.80 (m, 2H), 7.56-7.46 (ra, 4H), 7.25-7.21 (ra, IH), 6.77 (d, J= 7.9 Hz, IH), 4.57 (t, J = 6.6 Hz, 2H), 3.96 (s, 3H), 3.48-3.45 (ra, 2H), 2.34-2.28 (m, 2H).

l-(7-bromo-l-(3-chloropropyl)-2-methyl-lH-indol-3-yl)etha none

[0290] Prepared according to TP3, see also Scheme 2, by using 7-bromo-2- methyl-1 //-indole (425 mg, 2.02 mmol), Et ₂ AlCl (3.0- mL, 1.0 M, 3.0 mmol), AcCl (0.21 mL, 2.9 mmol) in CH ₂ Cl ₂ (10 mL) and Cs ₂ CO ₃ (1.61 g, 4.94 mmol), l-chloro-3-iodopropane (0.68 mL, 6.3 mmol) in CH ₃ CN (10 mL) to give the title compound (449 mg, 68% over two steps).

[0291] ¹ H NMR (400 MHz, CDCl ₃ ) δ 7. 98 (dd, J= 8.1 , 1.0 Hz, IH) ₅ 7.36 (dd, J = 7.7, 1.0 Hz, IH), 7.02 (dd, J= 8.1, 7.7 Hz, IH), 4.66-4.63 (m, 2H), 3.59 (t, J= 6.1 Hz, 2H), 2.72 (s, 3H), 2.60 (s, 3H) ₅ 2.24-2.17 (m, 2H).

[0292] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 194.0, 145.4, 131.9, 129.7, 127.9, 122.6, 120.1, 114.9, 103.2, 41.4, 41.3, 33.8, 31.7, 12.5.

W

1 -(I -fS-chloroproDviyy-ethyl-lH-indol-3-vPethanone

[0293] Prepared according to TP3, see also Scheme 2, by using 7-ethyl-l //-indole (307 mg, 2.11 mmol), Et ₂ AlCl (3.2 mL, 1.0 M, 3.2 mmol), AcCl (0.23 mL, 3.2 mmol) in CH ₂ Cl ₂ (10 mL) and Cs ₂ CO ₃ (1.38 g, 4.26 mmol), l-chloro-3-iodopropane (0.68 mL, 6.3 mmol) in CH ₃ CN (10 mL) to give the title compound (334 mg, 60% over two steps).

[0294] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.34 (dd, J = 8.0, 1.3 Hz, IH) ₅ 7.73 (s, IH), 7.23-7.19 (m, IH), 7.10-7.08 (m, IH), 4.49 (t, J= 6.8 Hz, 2H) ₃ 3.49-3.46 (m, 2H), 3.04-2.98 (m, 2H) ₅ 2.49 (s, 3H) ₅ 2.27-2.21 (m, 2H) ₅ 1.34 (t, J= 7.5 Hz, 3H).

[0295] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 192.6, 136.7, 134.1 , 127.7, 127.3, 124.4, 122.7, 120.4, 116.8, 46.2, 41.2, 33.8, 27.3, 25.1, 15.8.

l-π-(3-chloro-2-methylpropyl>7-methoxy-lH-indol-3-y0e thanone

[0296] Prepared according to TP3, see also Scheme 2, by using 7-methoxy-lH- indole (669 mg, 4.55 mmol), Et ₂ AlCl (6.8 mL, 1.0 M, 6.8 mmol), AcCl (0.49 mL, 6.8 mmol) in CH ₂ Cl ₂ (15 mL) and Cs ₂ CO ₃ (1.99 g, 6.13 mmol), l-chloro-3-iodo-2-methylpropane (0.94 mL, 8.0 mmol) in CH ₃ CN (20 mL) to give the title compound (589 mg, 70% over two steps).

[0297] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.00 (dd, J= 8.I ₅ 0.9 Hz, IH), 7.61 (s, IH), 7.17-7.12 (m, IH), 6.69-6.67 (m, IH), 4.38-4.24 (m, 2H), 3.90 (s, 3H) ₅ 3.46-3.34 (m, 2H), 2.51-2.46 (m, 4H), 1.02 (d, J= 6.8 Hz, 3H).

[0298] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 192.6, 146.9, 136.1, 128.6, 126.O ₅ 123.0, 1 16.5, 114.8, 104.0, 55.1, 52.5, 47.8, 36.7, 27.3, 15.0.

1 -( 1 -Q-chloropropyP^-methoxy- 1 H-indol-3-yl)-2-phenylethanone

[0299] Prepared according to TP3, see also Scheme 2, by using 7-methoxy- 1 H- indole (286 mg, 1.94 mmol), Et ₂ AlCl (3.0 mL, 1.0 M ₃ 3.0 mmol), 2-phenylacetyl chloride (0.39 mL, 3.0 mmol) in CH ₂ Cl ₂ (10 mL) and Cs ₂ CO ₃ (1.50 g, 4.63 mmol), l-chloro-3- iodopropane (0.70 mL, 6.5 mmol) in CH ₃ CN (10 mL) to give the title compound (332 mg, 50% over two steps).

[0300] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.06 (dd, J= 8.1 , 0.9 Hz, IH), 7.72 (s, IH), 7.36-7.16 (m, 6H) ₅ 6.72-6.70 (m, IH), 4.55 (t, J - 6.4 Hz, 2H), 4.1 1 (s, 2H), 3.92 (s, 3H), 3.41-3.38 (m ₅ 2H), 2.31-2.24 (m, 2H).

[0301] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 192.5, 146.9, 136.2, 135.8, 129.2, 129.2, 128.4, 126.4, 125.8, 123.3, 115.9, 1 15.2, 104.2, 55.2, 47.0, 46.9, 41.5, 33.6.

1 -(3 -chloropropyl)-7-methox v- 1 //-indole

[0302] A dry round bottomed flask was charged with KOH (574 mg, 10.2 mmol) which was finely ground under Ar. To this powder was added DMSO (15 mL) and 7- methoxy-lH-indoIe (0.90 mL, 6.89 mmol). The suspension was submitted to ultrasound irradiation for 30 min and cooled to 0 ⁰ C. To this mixture was added l-bromo-3- chloropropane (2.00 mL, 20.3 mmol) and the mixture was left with stirring overnight. The solution was poured into ice-water (25 mL) and extracted with EtOAc (4x 50 mL). The combined organic layers were washed with H ₂ O ₅ brine, dried over Na ₂ SO ₄ and adsorbed onto celite. Purification was by flash chromatography (heptanes — > heptanes:EtOAc 4:1) to give the title compound (1.40 g, 91%).

[0303] ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.20 (dd, J = 8.0, 0.9 Hz ₅ IH), 7.03-6.97 (m, 2H), 6.63-6.61 (m, IH), 6.43 (d, J= 3.1 Hz, IH), 4.54 (t, J= 6.4 Hz, 2H), 3.93 (s, 3H), 3.46-3.43 (m, 2H), 2.30-2.24 (m, 2H).

[0304] ¹³ C NMR (IOO MHz, CDCl ₃ ) δ 147.4, 131.2, 129.3, 1 19.9, 1 13.8, 1 13.8, 102.2, 101.3, 55.2, 46.1, 42.1, 34.6.

1 -(3 -chloropropyl)-7-ethyl-l //-indole

[0305] A dry round bottomed flask was charged with KOH (1.10 g, 19.7 mmol) which was finely ground under Ar. To this powder was added DMSO (30 mL) and 7-ethyl- lH-indole (2.00 mL, 14.6 mmol). The suspension was submitted to ultrasound irradiation for 30 min and cooled to 0 ⁰ C. To this mixture was added l-bromo-3-chloropropane (4.30 mL, 43.7 mmol) and the mixture was left with stirring overnight. The solution was poured into ice-water (25 mL) and extracted with EtOAc (4x 50 mL). The combined organic layers were washed with H ₂ O, brine, dried over Na ₂ SO ₄ and adsorbed onto celite. Purification was by flash chromatography (heptanes — » heptanes: EtOAc 10:1) to give the title compound (875 mg, 20%).

[0306] ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.48 (dd, J = 7.6, 1.5 Hz, I H), 7.08-6.99 (m, 3H), 6.50 (d, J= 6.5 Hz, IH), 4.48 (t, J= 6.7 Hz, 2H), 3.48-3.45 (m, 2H), 3.07-3.01 (m, 2H), 2.25-2.17 (m, 2H), 1.36 (t, J= 7.5 Hz, 3H).

[0307] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 130.3, 129.8, 127.2, 122.7, 1 19.9, 1 19.1, 102.1, 45.5, 41.8, 34.5, 25.6, 15.9. (signal for C _7b was not observed).

l-(3-chloropropyl)-iV-r3,4-dichlorobenzyl)-7-ethyl-li/-in dole-3-carboxamide

[0308] Prepared according to TP5, see also Scheme 4, by using MgI ₂ (559 mg, 2.01 mmol), 1 -(3 -chloropropyl)-7-ethyl-l //-indole (430 mg, 1.94 mmol), l,2-dichloro-4- (isocyanatomethyl)benzene (0.30 mL, 2.0 mmol) in DCE (4 mL) to give the title compound as off-white crystals (564 mg, 69%). •

[0309J ¹ H NMR (400 MHz ₃ dmso-d ₆ ) δ 8.05-8.47 (m, IH), 8.51-8.03 (m, IH) ₅ 7.99 (s, IH), 7.57-7.57-7.54 (m, 2H), 7.33-7.30 (m, IH), 7.07-6.98 (m, 2H), 4.46-4.42 (m, 4H), 3.68-3.65 (m, 2H), 3.03-2.99 (m, 2H), 2.23-2.18 (m, 2H), 1.27-1.23 (m, 3H).

[0310] ¹³ C NMR (100 MHz ₅ dmso-de) δ 165.0, 142.4, 134.3, 133.1, 131.5, 131.1 , 129.9, 129.8, 128.7, 128.3, 128.2, 123.9, 121.8, 120.0, 1 10.4, 46.7, 43.1, 41.7, 34.8, 25.4, 16.7.

N-benzy 1- 1 -(3 -chloropropyl)-7-eth yl- 1 H-indole-3 -carboxamide

[0311] Prepared according to TP5, see also Scheme 4, by using MgI ₂ (570 mg, 2.05 mmol), l-(3-chloropropyl)-7-ethyl-l//-indole (430 mg, 1.94 mmol), (isocyanatomethyl)benzene (0.27 mL, 2.2 mmol) in DCE (4 mL) to give the title compound as off-white crystals (445 mg, 65%).

(0312J ¹ H NMR (400 MHz ₅ dmso-d ₆ ) δ 8.42^8.39 (m, IH) ₅ 8.08-8.06 (m ₅ IH) ₅ 8.00 (s, IH), 7.33-7.28 (m, 4H) ₅ 7.23-7.19 (m, I H), 7.06-6.97 (m, 2H), 4.46-4.42 (m, 4H), 3.68-3.65 (m, 2H), 3.03-2.99 (m, 2H), 2.23-2.18 (m, 2H), 1.27-1.23 (m ₅ 3H).

[0313] ¹³ C NMR (I OO MHZ, dmso-d _δ ) δ 164.9, 141.0, 134.3, 133.0, 128.9, 128.8, 128.1 , 127.9, 127.3, 123.9, 121.6, 120.1, 110.7, 46.7, 43.1, 42.6, 34.8, 25.4, 16.7.

1 -(3-chloropropylV7-methoxy-iV-(3-methylbenzyl)- 1 H-indole-3-carboxamide

[0314] Prepared according to TP5, see also Scheme 4, by using MgI ₂ (681 mg, 2.45 mmol), 1 -(3 -chloropropyl)-7-methoxy-l //-indole (538 mg, 2.40 mmol), 1- (isocyanatomethy])-3-methylbenzene (0.34 mL, 2.45 mmol) in DCE (5 mL) to give the title compound as colorless crystals after flash chromatography (heptanes — > heptanes:EtOAc 7:3) followed by recrystallization from EtOAc / heptanes (438 mg, 49%).

[0315] ¹ H NMR (400 MHz, dmso-d ₆ ) δ 8.35-8.32 (m, IH), 7.93 (s, IH), 7.76-7.73 (m, IH), 7.20-7.17 (m, IH), 7.12-7.10 (m, 2H), 7.04-7.00 (m, 2H), 6.72 (d, J= 7.6 Hz, IH), 4.49-4.40 (m, 4H), 3.88 (s, 3H), 3.60-3.57 (m, 2H), 2.27 (s, 3H), 2.23-2.18 (m, 2H).

1 -(3-chloropropyl)-N-(3-fluorobenzyl)-7-methoxy- 1 H-indole-3-carboxamide

[0316] Prepared according to TP5, see also Scheme 4, by using MgI ₂ (745 mg, 2.68 mmol), l-(3-chloropropyl)-7-methoxy-l //-indole (600 mg, 2.68 mmol), l-fluoro-3-

(isocyanatomethyl)benzene (0.34 mL, 2.68 mmol) in DCE (5 mL) to give the title compound as colorless crystals after flash chromatography (heptanes — » heptanes :EtOAc 7:3) followed by recrystallization from EtOAc / heptanes (531 mg, 53%) as a 1:1 mixture of the chloride and the iodide.

[0317] ¹ H NMR (400 MHz, dmso-d ₆ ) δ 8.44-8.41 (m, IH), 7.94 (s, 1 H), 7.75-7.72 (m, IH), 7.37-7.32 (m, IH), 7.17-7.10 (m, 2H), 7.06-7.00 (m, 2H), 6.73 (d, J = 7.6 Hz, IH), 4.50-4.40 (m, 4H), 3.89 (s, 3H) ₅ 3.59 (t, J= 6.2 Hz, 2H), 2.26-2.19 (m, 2H).

l-( ^" 3-chloroρropyl)-7-methoxy-λ ^r -(2-methylbenzyl ^' )-lH-indole-3-carboxamide

[0318] Prepared according to TP5, see also Scheme 4, by using MgI ₂ (745 mg, 2.68 mmol), l-(3-chloropropyl)-7-methoxy-lH-indole (600 mg, 2.68 mmol), 1- (isocyanatomethyl)-2-methylbenzene (0.37 mL, 2.68 mmol) in DCE (5 mL) to give the title compound as colorless crystals after flash chromatography (heptanes — » heptanes -.EtOAc 7:3) followed by recrystallization from EtOAc / heptanes (390 mg, 39%).

[0319] ¹ H NMR (400 MHz, dmso-d ₆ ) δ 8.23-8.20 (m, 1 H), 7.96 (s, 1 H), 7.76-7.73 (m, IH), 7.28-7.26 (m, IH), 7.14-7.1 1 (3H), 7.03-6.99 (m, IH), 6.72 (d, J = 7.6 Hz, IH), 4.49-4.39 (m, 4H), 3.88 (s, 3H), 3.60-3.57 (m, 2H), 2.31 (s, 3H), 2.26-2.20 (m, 2H).

7-Cvano- lH-indole

[0320] Pd(PPh ₃ ) ₄ (103 mg, 0.09 mmol) was added to 7-bromo-l //-indole (588 mg, 3 mmol) and Zn(CN) ₂ in degassed DMF (10 ml). The vial was capped and heated in the MW at 170 ⁰ C for 15 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated in vacuo. The product

was purified by column chromatography (heptane 100% to heptane/EtOAc 9:1) followed by recrystallization from heptane. Yield: 350 mg (82%).

[0321] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ 8.74 (br s, IH), 7.86 (d, IH, J = 8.0 Hz), 7.52 (d, IH, J= 7.6 Hz), 7.34 (t, IH, J= 2.6 Hz), 7.17 (t, IH ₅ J= 8.0 Hz), 6.65 (m, IH).

3 -acetyl- 1 -(3-chloropropyI)- 7-cvano-indole

[0322] Preperad accordingly to TP3, see also Scheme 2, using 7-cyano-l //-indole (350 mg, 2.45 mmol), Et ₂ AlCl (3.7 mL, 1.0 M, 3.7 mmol), acetyl chloride (0.22 mL, 3.7 mmol) in CH ₂ Cl ₂ (10 mL) and Cs ₂ CO ₃ (0.88 g, 2.7 mmol), NaI (10 mg), l-chloro-3- iodopropane (0.43 mL, 4.1 mmol) in DMF (10 mL), 45 min at 100 ⁰ C to give the title compound (280 mg, 43% over two steps).

[0323] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.70 (m, IH), 7.84 (s, IH), 7.62 (m, IH), 7.33 (t, 1 H, J = 8 Hz), 4.73 (t, 2H, J= 6.8 Hz), 3.55 (t, 2H, J= 5.6 Hz), 2.54 (s, 3H) ₅ 2.42 (m, 2H).

1 -(I -( ^" 3-Chloropropyl)-7-methoxy-l/-/-indol-3-yl)ethanone

[0324] Prepared according to TPl, see also Scheme 1, using l-(7-methoxy-l//- indol-3-yl)ethanone (500 mg, 2.65 mmol), Cs ₂ CO ₃ (1.73 g, 5.3 mmol), NaI (cat) and 1- chloro-3-iodopropane (827 μmol, 7.94) in dry CH ₃ CN (10 ml). Purification by flash

chromatography (heptane/ethyl acetate 99:1-1:1) gave 675 mg (97%) of title compound as white crystals.

[0325] ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.97 (d, IH, J= 8.0 Hz), 7.67 (s, IH), 7.18 (t, IH ₅ J= 8 Hz), 6.72 (d, IH J= 7.8 Hz), 4.58 (t, 2H, J= 6.4 Hz), 3.94 (s, 3H), 3.47 (t, 2 H, J = 6.0 Hz), 2.51 (s, 3H), 2.32 (m, 2H).

1 -D-chloropropyD-N-methoxy-N-methyl-I H-indole-3-carboxamide

[0326] Prepared according to TP3, see also Scheme 2, from N-methoxy-N- methyl-1 H-indole-3-carboxamide (865 mg, 4.24 mmol). The product was purified by flash chromatography 0-40 % EtOAc in heptane to yield the title compound: 886 mg (75%).

[0327] ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.41 (d, J = 8.0 Hz, IH), 7.96 (s, IH), 7.41- 7.25 (m, 3H) ₅ 4.41 (t, J = 6.7 Hz, 2H), 3.77 (s, 3H), 3.45 (d, J = 6.7 Hz, 2H), 3.40 (s, 3H), 2.31 (pent, J= 6.7 Hz, 2H).

Amines

1 -(3-phenoxypropyl>-l ,4-diazepane

[0328] Prepared according to TP9, see also Scheme 7, by using lert-butyl 1,4- diazepane-1-carboxylate (390 mg, 1.95 mmol), (3-bromopropoxy)benzene (598 mg, 2.78 mmol), Cs ₂ CO ₃ (1.03 g, 3.17 mmol) to give the title compound (343 mg, 75%).

[0329] ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.29-7.25 (m, 2H), 6.94-6.89 (m, 3H), 4.03-4.00 (m, 2H), 3.01-2.95 (m, 4H), 2.75-2.68 (m, 6H), 1.96-1.91 (m, 2H), 1.85-1.79 (m, 2H).

[0330] ¹³ C NMR (100 MHz, CDCl ₃ ) δ 159.3, 129.6, 120.8, 1 14.8, 66.3, 57.4, 55.1 , 54.6, 48.8, 47.1 , 29.9, 27.8.

S-Q-^-fluorophenoxy^ethyiyS^-diazabicvclop.σ.1]octane

[0331] Prepared according to TP9, see also Scheme 7, by using tert-butyl 3,8- diazabicyclo[3.2.1]octane-8-carboxylate (248 mg, 1.17 mmol), l-(2-bromoethoxy)-4- fluorobenzene (384 mg, 1.75 mmol), Cs ₂ CO ₃ (571 mg, 1.75 mmol) in CH ₃ CN (10 mL) to give the title compound (188 mg, 64%).

[0332] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ 6.89-6.84 (m, 2H) ₅ 6.75-6.72 (m, 2H), 3.92-3.89 (m, 2H), 3.33-3.30 (m, 2H), 2.64-2.60 (m, 4H) ₃ 2.55 (br s, IH) ₅ 2.25-2.23 (m, 2H), 1.77-1.75 (m, 2H), 1.63-1.59 (m, 2H).

4-(3-chlorophenoxy)piperidine

[0333] Prepared according to TP6, see also Scheme 5, from tert-butyl 4- hydroxypiperidine-l -carboxylate (400 mg, 2 mmol) and 3-chlorophenol (358 mg, 2.8 mmol). The crude product was purified by flash chromatography 0-20 % EtOAc in heptane. The resulting product was dissolved in CH ₂ Cl ₂ (10 mL) and TFA (5 mL) was cautiously added. After stirring at room temperature for 3 h the mixture was evaporated to dryness. The crude product was dissolved in a minimal amount of MeOH and purified by solid phase extraction using a SCX cartridge eluding with NH ₃ (MeOH) to give the title compound 304 mg (72% over two steps).

[0334] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.11 - 7.06 (m, IH), 6.97 - 6.85 (m, 2H), 6.71 - 6.69 (m, IH), 4.44 - 4.40 (m, IH), 3.71 - 3.63 (m, 2H), 3.42 - 3.37 (m, 2H), 1.95 - 1.88 (m, 2H) ₅ 1.79 - 1.72 (m, 2H).

4-(2-phenoxyethvDpiρeridine

[0335] Prepared according to TP6, see also Scheme 5, using tert-butyl 4-(2- hydroxyethyl)piperidine-l-carboxylate (458 mg, 2 mmol) and phenol (263 mg, 2.8 mmol). The crude product was purified by flash chromatography 0-20 % EtOAc in heptane. The resulting product was dissolved in CH ₂ C1 ₂ (10 mL) and TFA (5 mL) was cautiously added. After stirring at room temperature for 3 h the mixture was evaporated to dryness. The crude product was dissolved in a minimal amount of MeOH and purified by solid phase extraction using a SCX cartridge eluding with NH ₃ (MeOH) to give the title compound 293 mg (56% over two steps).

[0336] ¹ H NMR (400 MHz, CDCl ₃ ) δ:7.31 -7.25 (m, 2H), 6.98 - 6.88 (m, 2H), 4.13 - 4.06 (m, 2H), 4.00 (t, J= 7.2 Hz, 2H), 2.78 - 2.69 (m, 2H), 1.78 - 1.65 (m, 5H) ₅ 1.23 - 1.19 (m, 2H).

[0337] ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 159.2, 129.6, 120.8, 1 14.7, 65.5, 46.6, 36.5, 33.3., 31.7.

4-(2-(4-chlorophenoxy)ethvI)piperidine

[0338] Prepared according to TP6, see also Scheme 5, from tert-butyl 4-(2- hydroxyethyl)piperidine-l-carboxylate (458 mg, 2 mmol) and 4-chlorophenol (361 mg, 2.8 mmol). The crude product was purified by flash chromatography 0-20 % EtOAc in heptane. The resulting product was dissolved in CH ₂ Cl ₂ (10 mL)- and TFA (5 mL) was cautiously added. After stirring at room temperature for 3 h the mixture was evaporated to dryness. The crude product was dissolved in a minimal amount of MeOH and purified by solid phase extraction using a SCX cartridge eluding with NH ₃ (MeOH) to give the title compound 406 mg (86% over two steps).

[0339] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.20 - 7.18 (m, 2H) ₅ 6.81 - 6.78 (m, 2H), 4.16 - 4.07 (m, 2H), 3.97 (t, J= 7.2 Hz, 2H), 2.74 - 2.67 (m, 2H), 1.77 - 1.60 (m, 5H), 1.20 - 1.11 (m, 2H).

tert-butyl 3β-hydroxy-8-azabicyclof3.2.1]octane-8-carboxylate

[0340] A reaction flask was charged with 3α-hydroxy-8-azabicyclo[3.2.1]octane- 8-carboxylic acid tert-butyl ester (3.94 g, 17.3 mmol), 4-nitrobenzoic acid (1 1.3 g, 67.8 mmol), PPh ₃ (18.8 g, 68.6 mmol) in dry THF (140 mL) and cooled to 0 ⁰ C. Diisopropylazodicarboxylate (13.8 mL, 70.1 mmol) was added drop wise over 15 min. After 1 h cooling was removed and the mixture stirred at rt overnight. The mixture was then stirred at 45 ⁰ C for 5 h followed by cooling to rt and the mixture was diluted with diethylether and washed with several portions of saturated aqueous NaHCO ₃ . The combined aqueous layers were extracted with diethyl ether and the combined organic layers dried over Na ₂ SO ₄ and evaporated to dryness. The resulting gum was stirred with diethyl ether (80 mL) while n- heptane (40 mL) was added slowly to cause crystallization. The mixture was filtered and the filter cake extracted with diethyl ethern-heptane 1 :1 (300 mL). The filtrate was adsorbed onto celite and purified by flash column chromatography (SiO ₂ ; n-heptane → n-heptane/ethyl acetate 7:3) to give the intermediate benzoic acid ester. The ester was dissolved in THF (40 mL) and LiOH-H ₂ O (0.60 g, 14.3 mmol) in water (7 mL) was added. After stirring at rt for 5 h saturated aqueous NaHCO ₃ was added and the mixture extracted with diethyl ether. The combined organic layers were washed with saturated aqueous NaHCO ₃ , brine, dried over Na ₂ SO ₄ and evaporated to dryness to give the title compound as colorless crystals (3.33 g, 82%).

(lR,3r,5S)-3-(4-fluorophenoxyy8-azabicvclo[3.2.1 ^" [octane

(0341] Prepared according to TP7, see also Scheme 5, from 4-fluorophenol (313 mg, 2.8 mmol) and tert-butyl 3β-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylale (451 mg, 2.0 mmol). Yield: 130 mg (29 % over two steps). /

[0342] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 6.95 - 6.90 (m, 2H), 6.78 - 6.72 (m, 2H), 4.53 - 4.49 (m, IH) ₅ 4.23 - 4.1 1 (m, 2H), 2.17 - 1.90 (m, 8H).

(lR,3r,5S)-3-(2-chlorophenoxyV8-azabicvclo| ^" 3.2.noctane

[0343] Prepared according to TP7, see also Scheme 5, from 2-chlorophenol (358 mg, 2.8 mmol) and tert-butyl 3β-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate (451 mg, 2.0 mmol). Yield: 263 mg (58 % over two steps).

[0344] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.34 (d, J = 6.6 Hz, IH), 7.18 (t, J = 6.6 Hz, IH), 6.83 (t, J- 6.6 Hz, IH), 6.79 (d, J = 6.6 Hz, IH), 4.64 - 4.60 (m, IH), 4.23 - 4.18 (m, 2H), 2.32 - 1.95 (m, 8H).

3-Ethoxycarbonylmethylene-8-azabicyclo[3.2.1 ^" |octane-8-carboxylic acid t-butyl ester

[0345] A reaction flask was charged with triethyl phosphonoacetate (7.458 g, 33.3 mmol) in dry THF (20 mL) under Argon. NaH (60% in mineral oil, 1.33 g, 33.3 mmol) was added in portions and the mixture was stirred at rt for 1 h. The clear solution was cooled to <10 ⁰ C with an icebath followed by dropwise addition of 3-oxo-8-azabicyclo[3.2.1]octane-8- carboxylic acid /-butyl ester (4.977 g, 22.2 mmol) dissolved in THF (5 mL) over 45 min. The temperature was slowly raised to rt and the reaction was stirred for another 20 h. The reaction mixture was quenched with water and the product extracted into ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and concentrated. The product was purified by flash column chromatography (SiO ₂ ; n-heptane/ethyl acetate 4: 1) to give the title compound: 5.416 g (82%).

[0346] ¹ H NMR (CDCl ₃ ) δ 5.76 - 5.74 (m, IH), 4.28 (br s, 2H), 4.19 - 4.07 (m 2), 3.66 - 3.59 (m, IH), 2.76 - 2.20 (m, 2H), 2.11 - 2.06 (m, IH) ₅ 1.93 - 1.87 (m, 2H), 1.58 - 1.54 (m, 2H), 1.46 (m, 9H), 1.26 (t, 3H).

(8-Azabicyclo[3.2.1 ^~ |oct-3-ylidene)acetic acid ethyl ester

[0347] To 2-ethoxycarbonylmethyIene-8-azabicyclo[3.2.1]octane-8-carbox ylic acid t-butyl ester (12.3 g, 41.8 mmol) in dichloromethane was added TFA (10 mL) and the reaction was stirred for 8 h. The solution was concentrated under reduced pressure, diluted with dichloromethane, and washed with 2 M NaOH followed by brine. The water phases were thereafter back-extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate, filtered, and concentrated. The crude product: 7.04 g (91%) was used without further purification.

(8-A2abicyelof3.2.11oct-3α-yl)acetic acid ethyl ester

[0348] A 250 mL reaction flask was charged with (8-azabicyclo[3.2. l]oct-3- ylidene)acetic acid ethyl ester (3.7 g, 19 mmol), ammonium formiate (14 g, 190 mmol), and Pd/C (0.32 g) in 150 mL MeOH. When all of the ammonium formiate was dissolved the mixture was degassed for 15 min. The reaction was stirred on under an inert atmosphere (N ₂ ) over night at rt. The mixture was filtered through celite, concentrated, diluted with 2 M NaOH (ca pH 10), and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated to give the crude product 3.1 g (83%; 85:15 α:β) that was used without further purification. Major isomer:

[0349] ¹ H NMR (CDCl ₃ ) δ 4.08 (q, J = 7.2 Hz ₃ 2 H), 3.45 - 3.41 (m, 2 H), 2.40 (d, J = 8.0 Hz, 2 H), 2.25 - 2.18 (m, 1 H), 2.06 - 1.96 (m, 2 H), 1.82 - 1.55 (m, 5 H), 1.31 - 1.23 (m, 2 H), 1.21 (t, J= 7.2 Hz, 3 H).

[0350] ¹³ C NMR (CDCl ₃ ) δ 173.3, 60.4, 53.6, 42.6, 36.7, 30.4, 25.4, 14.4.

3α-Ethoxycarbonylmethyl-8-azabicvclor3.2.11octane-8-carb oxγlic acid tert-butyl ester

[0351] A solution of di-/er?-butyldicarbonate (4.3 g, 20 mmol) in THF (10 mL) was added to a cooled (ice water bath) solution of (8-azabicyclo[3.2.1]oct-3α-yl)acetic acid ethyl ester (2.8 g, 14 mmol) in THF (40 mL): The reaction was stirred at rt for 14 h and then concentrated. The semi-solid residue was diluted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and concentrated. The oily residue was purified by flash column chromatography (SiO ₂ ; heptane/ethyl acetate 7:3) to yield the title compound: 3.8 g (73%) as an oil. Major isomer:

[0352] ¹ H NMR (CDCl ₃ ) δ 4.16 (vbr s, 2 H), 4.1 1 (q, J= 6.8 Hz, 2 H), 2.43 (d, J = 7.6 Hz ₃ 2 H), 2.24 - 2.12 (m, 3 H), 2.00 - 1.92 (m, 2 H), 1.70 - 1.61 (M, 2 H), 1.44 (s, 9 H), 1.23 (t, J= 6.8 Hz, 3 H).

F(lR,5SV8-(tert-butoxycarbonvi>-8-azabicyclo[3.2.1]oct -3 α -yl]acetic acid

[0353] 3α-Ethoxycarbonylmethyl-8-azabicyclo[3.2.1]octane-8-carboxy lic acid tert-butyl ester (5.38 g, 18 mmol) was taken up in THF (30 mL) and NaOH (2M, 20 mL) and the reaction mixture was stirred at rt for 48 h. The THF was distilled off and the aq. phase made acidic with HCl (pH=2) before extraction of the product with ether. The organic phase was dried over Na ₂ SO ₄ and concentrated in vacuo. Yield: 4.87 g (99%).

[0354] Prepared according to TPlO, see also Scheme 8, from ftlR,5S)-8-(tert- butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3 α -yl]acetic acid (1.34 g, 5 mmol) and 4- chlorophenylmagnesium chloride (10 mL, 1 M, 10 mmol). After extractive work up the product was purified by flash chromatography 0-20 % EtOAc in heptane. Yield 1.48 g (82 %). The product (386 mg, 1 mmol) was taken up in a mixture of TFA (2 mL) and DCM (2 mL) and and stirred for 1 h at rt,concentrated in vacuo, then taken up in EtOAc, washed with NaOH (2 N), dried over Na ₂ SO ₄ and concentrated in vacuo. Yield: 278 mg (97 %).

[0355] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.84 (d, J = 6.8 Hz, 2H), 7.45 (d, J = 6.8 Hz, 2H), 4.21 - 4.11 (m, 2H), 3.09 - 3.02 (m, 2H), 2.38 - 1.93 (m, 4H), 1.71 - 1.63 (m, 3H), 1.24 - 1.19 (m, 2H).

[0356] ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 198.8, 139.7, 135.6, 129.7, 129.2, 56.5, 53.6, 36.9, 30.5, 24.5.

πR.3r.SSV3-(4-chlorophenethylV8-azabicvclor3.2.noctane

[0357] Prepared according to TPl 1, see also Scheme 9, from (lR,3r,5S)-tert-butyl 3-(2-(4-chlorophenyl)-2-oxoethyl)-8-azabicyclo[3.2.1]octane- 8-carboxylate (928 mg, 2.6 mmol). After extractive workup, the product was purified by SCX. Yield: 310 mg (48%).

[0358] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.24 - 7.20 (m, 2H) ₅ 7.07 - 7.01 (m, 2H), 3.52 - 3.43 (m, 2H), 2.55 - 2.50 (m, IH), 2.07 - 1.98 (m, 2H), 1.80 - 1.66 (m, 6H), 1.32 - 1.27 (m, 2H).

2-rπR,3r _> 5SV8-azabicvcloC3.2.11octan-3-ylVl-(3.4-dichlorophenyl)ethan one

[0359] Prepared according to TPlO, see also Scheme 8, from JχiR,5S)-8-(tert- butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3 α -yl]acetic acid (468 mg, 1.5 mmol) and 3,4- dichlorophenyl magnesium chloride (6 mL, 0.5 M, 3 mmol). After extractive work up the product was purified by flash chromatography 0-20 % EtOAc in heptane. The product was

taken up in a mixture of TFA (2 mL) and DCM (2 mL), stirred for 1 h at rt and purified by SCX. Yield: 300 mg (68 %).

[0360] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.97 (d, J = 2.0 Hz, IH), 7.72 (dd, J= 2.0 and 8.6 Hz, IH), 7.52 (d, J= 8.6 Hz, IH), 3.56 - 3.54 (m, 2H), 3.04 (d, J= 7.5 Hz, 2H), 2.50 - 2.45 (m, 1 H), 2.18 - 2.1 1 (m, 2H), 1.92 - 1.89 (m, 2H), 1.77 - 1.74 (m, 2H), 1.34 - 1.29 (m, 2H).

[03611 ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 197.6, 137.8, 136.8, 133.6, 131.0, 130.3, 127.3, 53.5, 46.4, 36.7, 30.3, 24.3.

[0362] Prepared according to TPlO, see also Scheme 8, from £(lR,5S)-8-(tert- butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3 a -yl]acetic acid (468 mg, 1.5 mmol) and 3,5- dichlorophenylmagnesium chloride (6 mL, 0.5 M, 3 mmol). After extractive work up the product was purified by flash chromatography 0-20 % EtOAc in heptane. The product was taken up in a mixture of TFA (2 mL) and DCM (2 mL), stirred for 1 h at rt and purified by SCX. Yield: 260 mg (58 %).

[0363] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.75 (d, J = 1.5 Hz, 2H), 7.58 (t, J = 1.5 Hz, IH), 4.05 - 3.98 (m, 2H) ₅ 4.36 (d, J = 7.8 Hz, 2H), 2.68 - 2.62 (m, IH), 2.53 - 2.45 (m, 2H) ₅ 2.34 - 2.29 (m, 2H), 2.05 - 1.97 (m, 2H), 1.67 - 1.60 (m, 2H).

[0364] ^{" 13} C NMR (100 MHz ₅ CDCl ₃ ) δ: 195.8, 139.0, 136.2, 133.4, 126.6, 54.2, 45.8, 33.0, 26.9, 22.8.

2-(πR,3r,5S)-8-azabicvclo[3.2.1]octan-3-yl)-l-(3-chlorop henyl)ethanone

[0365] Prepared according to TPlO, see also Scheme 8, from ftlR,5S)-8-(tert- butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3 α -yl]acetic acid (468 mg, 1.5 mmol) and 3-

chlorophenylmagnesium chloride (6 mL, 0.5 M ₅ 3 mmol). After extractive work up the product was purified by flash chromatography 0-20 % EtOAc in heptane. The product was taken up in a mixture of TFA (2 mL) and DCM (2 mL), stirred for 1 h at rt and purified by SCX. Yield: 290 mg (66 %).

[0366] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.91 - 7.86 (m, IH) ₅ 7.82 - 7.76 (m, 1 H), 7.57 - 7.52 (m, IH), 7.44 - 7.38 (m, IH), 4.02 - 3.98 (m, 2H), 3.22 - 3.18 (m, 2H), 2.27 - 2.65 (m, IH), 2.54 - 2.46 (m, 2H), 2.33 - 2.21 (m, 2H), 2.02 - 1.97 (m, 2H), 1.85 - 1.80 (m, 2H).

[0367] ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 196.5, 138.2, 135.1 , 134.7, 131.9, 128.2, 126.3, 55.4, 46.0, 32.2, 26.4, 23.4.

2-rπR.3r.5SV8-azabicvclop.2.11octan-3-vn-l-φyridin-2-vn ethanone

[0368] Prepared according to TPl O, see also Scheme 8, from JXlR,5S)-8-(tert- butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3 α -yl]acetic acid (468 mg, 1.5 mmol) and 2- pyridininmagnesium chloride (12 mL, 0.25 M ₃ 3 mmol). After extractive work up the product was purified by flash chromatography 0-20 % EtOAc in heptane. The product was taken up in a mixture of TFA (2 mL) and DCM (2 mL), stirred for 1 h at rt andpurified by SCX. Yield: 172 mg (50 %).

[0369] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.66 - 8.65 (m, IH), 8.01 - 7.99 (m, IH), 7.83 - 7.79 (m ₅ IH), 7.46 - 7.43 (m, IH), 3.59 - 3.53 (m, 2H), 3.39 - 3.37 (m, 2H) ₅ 2.59 - 2.50 (m, IH), 2.17 - 2.10 (m, 2H), 1.93 - 1.86 (m ₅ 4H), 1.42, - 1.38 (m, 2H).

[0370] ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 201.8, 153.8, 149.2, 137.1, 127.3, 122.1 , 54.9, 45.2, 36.5, 29.8, 29.0, 28.9, 24.3.

2-r(lR,3r,5S)-8-azabicvclo[ ^" 3.2.11octan-3-yl)-l-(3-chloro-4-fluorophenyπethanone

[0371] Prepared according to TPlO, see also Scheme 8, from £(lR,5S)-8-(tert- butoxycarbonyl)-8-azabicyclo[3.2.1]oct-3 α -yl]acetic acid (468 mg, 1.5 mmol) and 3-chloro- 4-fluorophenylmagnesium chloride (6 mL, 0.5 M, 3 mmol). After extractive work up the product was purified by flash chromatography 0-20 % EtOAc in heptane. The product was taken up in a mixture of TFA (2 mL) and DCM (2 mL), stirred for 1 h at rt and purified by SCX. Yield: 122 mg (21 %).

[0372] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.00 - 7.97 (m, IH) ₅ 7.84 ^' - 7.80 (m, IH), 7.26 - 7.19 (m, IH), 3.57 - 3.55 (m, 2H), 3.10 - 3.04 (m, 2H), 2.48 - 2.46 (m, IH), 2.19 - 2.17 (m, 2H) ₃ 1.93 - 1.89 (m, 2H), 1.79 - 1.77 (m, 2H), 1.35 - 1.31 (m, 2H).

[0373] ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 198.0, 134.3, 131.2, 128.6, 128.5, 1 17.2, 1 16.9, 53.5, 46.4, 36.7, 30.4. 24.3.

1 -(2-(4-fluorophenoxy)ethyl ^' )-K4-diazepane

[0374] Prepared according to TP9, see also Scheme 7, from tert-butyl 1,4- diazepane-1 -carboxylate (400 mg, 2 mmol), l-(2-bromoethoxy)-4-fluorobenzene (569 mg, 2.6 mmol). Yield: 450 mg (94 %).

[0375] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 6.96 -6.91 (m, 2H), 6.82 - 6.79 (m, 2H), 4.38 - 3.34 (m, 2H), 4.00 (t, J =5.4 Hz ₅ 2H) ₅ 3.05 - 3.00 (m, 2H), 2.95 - 2.80 (m, 4H), 1.86 - 1.83 (m, 2H).

[0376] ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 162.5, 158.7, 156.3, 155.1 , 1 16.1 , 1 15.9, 1 15.8, 115.7, 67.3, 56.7, 55.8, 54.9, 47.8, 46.3, 28.6.

1 -f2-phenoxyethyl ^' )-l ,4-diazepane

[0377] Prepared according to TP9, see also Scheme 7 from /er/-butyl 1,4- diazepane-1-carboxylate (400 mg, 2 mmol), (2-bromoethoxy)benzene (569 mg, 2.6 mmol). Yield: 377 mg (86 %).

[0378] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.28 - 7.24 (m, 2H), 6.95 - 6.86 (m, 3H), 5.22 - 5.20 (m, 2H), 4.06 -4.03 (m, 2H), 3.09 - 2.82 (8H), 1.91 - 1.85 (m, 2H).

[0379] ¹³ C NMR (100 MHz ₅ CDCl ₃ ) δ: 158.9, 129.7, 121.1, 114.8, 66.6, 57.0, 55.0, 54.8, 47.8, 46.1, 28.2.

3-Trifluorosulfonγl-8-tertButyloxycarbonyl-8-azabicyclof3.2 .11-oct-2-ene (N-Boc- nortropanone enol triflate ^" )

[0380] LDA was generated by adding BuLi (20 mL, 1.68M, 32.6 mmol) to a solution of diisopropylamine (2.38 g, 32.6 mmol) in dry THF (1OmL) at -78 ⁰ C under argon. The mixture was kept at that temperature for 30 min followed by the addition of a solution of N-Bocnortropinone (5.27 g, 23.4 mmol) in dry THF (20 mL). The mixture was then left stirring for Ih while maintaining the temperature at 78 ⁰ C. Then a solution of 2-[N ₅ N- Bis(trifluoromethylsulfonyl)amino]-5-chloropyridine (10.08 g, 25.7 mmol) in dry THF (20 mL) was added and the mixture was slowly allowed to reach room temperature overnight and subsequently concentrated and purified by flash chromatography (EtO Ac/heptane 1 :6,) to give the title compound 6.68 g (80%) which on prolonged standing crystallised into a white solid.

[0381] ¹ H NMR (CDCl ₃ ) δ 6.10 (bs, IH), 4.42 (m, 2H), 3.05 (bs, IH), 2.23 (m, IH), 2.07 (d, J=I 6.6Hz, IH), 1.93-2.03 (m ₃ 2H), 1.72 (m, IH), 1.43 (s, 9H).

[0382] ¹³ C NMR (CDCl ₃ ) δ 153.9, 148.0, 124.0, 1 18.7, 80.5, 51.9, 36.5, 34.7, 30.1, 28.4. .

tert-butyl (lR,5S)-3-pentyl-8-azabicyclof3.2.1 ^" loctane-8-carboxylate

[0383] In a dry argon flushed schlenk flask palladium acetate (220 mg, 0.98 mmol) and tricyclohexyl phosphine (549 mg, 1.96 mmol) were dissolved in THF (40 mL) and NMP (20 mL). After 5 min S-trifluorosulfonyl-S-tertButyloxycarbonyl-δ- azabicyclo[3.2.1]-oct-2-ene (N-Boc-nortropanone enol triflate) (7.0 g, 19.6 mmol) and NMI (1.72 g, 21 mmol) were added. In a second dry argon flushed flask pentyl magnesium bromide (2M, 14 rnL, 28 mmol) was transmetallated to the corresponding zinc reagent with ZnBr ₂ (1.5 M, 18.6 mL, 28 mmol) at it. The formed pentyl zinc reagent was added to the reaction mixture (exothermic). The reaction was heated to 80 ⁰ C for 16 h, then quenched with MeOH (10 mL) and filtered through celite. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % EtOAc in heptane. Yield: 1.92 g (73%).

[0384] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ: 5.67 (bs, IH), 4.38-4.17 (m, 2H), 2.78- 2.60 (m, IH), 2.19-2.06 (m, IH), 1.98-1.55 (m, 6H), 1.43 (s, 9H), 1.38-1.17 (m, 6H), 0.87 (t, J=7.2 Hz, 3H).

πR,5S)-3α-pentyl-8-azabicyclor3.2.πoctane

[0385] tert-butyl (lR,5S)-3-pentyl-8-azabicyclo[3.2.1]octane-8-carboxylate (450 mg, 1.7 mmol) was dissolved in DCM (2 mL) and TFA (2mL) and left stirring for 1 h, concentrated in vacuo. The crude product was redissolved in EtOAc and washed with NaOH (2 M, aq.), dried over sodium sulphate, filtered and concentrated in vacuo. Platinum oxide (34 mg), acetic acid (100 mg, 1.7 mmol) and MeOH were added, the flask was evacuated and flushed with H ₂ . The reaction was stirred for 2 h at rt then filtered through celite and

concentrated in vacuo. The concentrate was taken up in DCM and washed with NaOH (2 M, aq.) dried over sodium sulphate, filtered and concentrated in vacuo. Yield: 272 mg (88%).

[0386] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ: 3.41 (bs, 2H), 1.95 (pentet, J = 6.9 Hz, 2H) ₅ 1.74-1.21 (m, 15H), 0.84 (t, J= 7.0 Hz, 3H).

[0387] ¹³ C NMR (100 MHZ, CDCl ₃ ) - major isomer: δ 53.7, 38.0, 37.4, 32.1 , 30.9, 28.5, 28.3, 22.8, 14.2.

l-π-r3-f4-butyl-l-ρiperidinyl)propyn-lH-indol-3-vn-etha none C900b

[0388] l-[l -(3-chloropropyl)-lH-indol-3-yl]-ethanone (235 mg, 1 mmol), cesium carbonate (650 mg, 2 mmol), potassium iodide (166 mg, 1 mmol) and 4-n-butylpiperidine (134 mg, 0.95 mmol) were weighed into a MW vial and dry MeCN (4 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction was repeated 4 times. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-10 % MeOH in DCM. Yield: 1.07 g (78%). LC/MS purity: UV/MS 100/100.

[0389] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.38-8.36 (m, IH), 7.82 (s, IH), 7.40-7.26 (m, 3H), 4.26 (t, J = 6.4 Hz, 2H), 2.88 (bd, 2H) ₅ 2.52 (s, 3H) ₅ 2.29 (t, J = 6.8 Hz, 2H), 2.08 (pentet, J= 6.8 Hz, 2H), 1.95 (bt, 2H), 1.71 (bd, 2H), 1.30-1.24 (m, 9H), 0.89 (t ₅ J= 6.8 Hz, 3H).

[0390] ¹³ C NMR (100 MHz, CDCl ₃ ); δ 193.1, 137.0, 135.6, 126.6, 123.4, 122.9, 122.7, 117.2, 1 10.0, 54.9, 54.1 , 44.7, 36.4, 35.9, 32.4, 29.2, 27.8, 26.8, 23.1, 14.3.

i-q-o-rαR.5S')-3 α -Q-phenvlethvlVδ-azabicvclorS.σ. lloct-δ-vnpropvU- 1 H-indol-3- vDethanone C616b

[0391] l-[l-(3-chloropropyl)-lH-indol-3-yl]-ethanone (117 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and (lR,5S)-3-(2- phenylethyl)-8-azabicyclo[3.2.1]octane (80 mg, 0.35 mmol) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 88 mg (57%). LC/MS purity: UV/MS 99/98.

[0392] ¹ H NMR (400 MHz ₃ CDCl ₃ ) δ: 8.39-8.37 (m, IH), 7.85 (s, IH), 7.42-7.16 (m, 8H), 4.33 (t, J= 6.6 Hz, 2H), 3.20 (bs, 2H), 2.62 (t, J= 7.2 Hz, 2H), 2.52 (s, 3H), 2.32 (t, J- 6.6 Hz, 2H), 2.25-2.17 (m, 2H), 2.03 (pentet, J= 6.6 Hz, 2H), 1.94-1.90 (m, 2H), 1.78 (t, J= 5.8 Hz, 2H) ₅ 1.68-1.38 (m, 5H).

[0393] l-[l-(3-chloropropyl)-lH-indol-3-yl]-ethanone (117 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and (lR,5S)-3- pentyl-8-azabicyclo[3.2.1]octane (81 mg, 0.45 mmol) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min.

The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 123 mg (72%). LC/MS purity: UV/MS 100/92.

[0394] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.39-8.36 (m, IH), 7.81 (s, IH), 7.43-7.26 (m, 3H), 4.33 (t, J= 6.6 Hz ₅ 2H) ₅ 3.12-3.09 (m, 2H) ₅ 2.52 (s, 3H), 2.24 (t, J = 6.6 Hz ₅ 2H), 2.15-2.09 (m, 2H) ₅ 1.96 (pentet, J = 6.6 Hz ₅ 2H), 1.90-1.87 (m, 2H), 1.74-1.22 (m, 13H) ₅ 0.89 (t, J= 7.0 Hz ₅ 3H).

[0395] ¹³ C NMR (100 MHz, CDCl ₃ ); δ 193.1, 137.1, 135.8, 126.6, 123.3, 122.8, 122.6, 117.0, 110.2, 58.8, 48.2, 44.6, 38.6, 36.I ₅ 32.2, 28.6, 28.6, 28.5, 27.7, 27.4, 22.9, 14.3.

N-(3-methylbenzyl ^' )-l-(3-|rπR.5SV3 α ^-phenylethylVS-azabicvclofS.σ.11oct-8-vnpropyU- lH-indole-3-carboxamide C296b

[0396] l-(3-chloropropyl)-N-(3-methylbenzyl>lH-indole-3-carboxam ide (1 17 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and (li?.,5ιS)-3-pentyl-8-azabicyclo[3.2.1]octane (80 mg, 0.35 mmol) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 74 mg (41%). LC/MS purity: UV/MS 100/92.

[0397] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.98-7.81 (m, 2H), 7.44-7.42 (m, IH), 7.29-7.10 (m, 1 IH) ₅ 6.15 (bt, IH), 4.66 (d, J= 5.6 Hz, 2H), 4.28 (t, J= 6.6 Hz, 2H), 3.22 (bs, 2H), 2.89 (t, J= 7.2 Hz, 2H), 2.62-2.58 (m, 2H), 2.37-1.36 (m, 14H), 1.27 (t, J= 7.2 Hz, 2H).

l-Cl-IS-^-G-methoxyphenylVl-piperidinyllpropyll-lH-indol- 3-vDethanone CβSgb

[0398] l-[l -(3-chloropropyl)-l H-indol-3-yl]-ethanone (1 17 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and 4-(2- methoxyphenyl)piperidine (86 mg, 0.45 mmol) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 125 mg (71%). LC/MS purity: UV/MS 99/86.

[0399] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.28-8.26 (m, 2H), 7.59 (dt, J = 8.0 and

1.0 Hz, IH), 7.34-7.13 (m, 4H), 6.94-6.88 (m, 2H), 4.40 (t, J = 6.8 Hz, 2H), 3.81 (s, 3H), 3.43-3.40 (m, 2H), 3.18-3.10 (m, IH), 2.97-2.93 (m, 2H) ₅ 2.78-2.75 (m, 2H), 2.54 (s, 3H), 2.34-2.30 (m, 2H), 1.95-1.89 (m, 4H).

l-(l-{3-r4-π.3-benzothiazol-2-vn-l-piperidinvnpropyU-lH- indol-3-yl)ethanone C667b

[0400] l-[l-(3-chloropropyl)-lH-indol-3-yl]-ethanone (117 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and 2-(4- piperidinyl)-l,3-benzothiazole (98 mg, 0.45 mmol) were weighed into a MW vial and dry

MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 100 mg (53%). LC/MS purity: UV/MS 98/84. [0401] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ: 8.26-8.24 (m, 2H), 7.96-7.90 (m, 2H), 7.58-7.22 (m, 5H), 4.39 (t, J= 6.8 Hz, 2H), 3.34-3.24 (m, 5H), 2.76-2.72 (m, 2H), 2.61-2.57 (m, 2H), 2.53 (s, 3H), 2.28-2.22 (m, 4H).

l-π-(3-r4-(4-fluorophenoxy)-l-piperidinyl1propyl)-lH-ind ol-3-yl)ethanone C656b

10402] l-[l-(3-chloropropyl)-lH-indol-3-yl]-ethanone (1 17 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and 4-(4- fluorophenoxy)piperidine (104 mg, 0.45 mmol) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 1 1 1 mg (63%). LC/MS purity: UV/MS 98/82.

[0403] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.25-8.22 (m, 2H), 7.55-7.53 (m, IH), 7.35-7.21 (m, 2H), 7.00-6.91 (m, 4H), 4.40-4.34 (m, 3H), 2.99-2.95 (m, 2H) ₅ 2.70-2.66 (m, 4H), 2.52 (s, 3H), 2.22-2.18 (m, 2H), 2.04-2.00 (m, 2H), 1.88-1.82 (m, 2H).

N-(3-chlorobenzyl)-l-(3-f ^' 4-r4-fluorophenoxyVl-piperidinyl]propyπ-lH-indole-3- carboxamide C292b

[0404] l-(3-chloropropyl)-N-(3-chlorobenzyl)-lH-indole-3-carboxamid e (180 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and 4-(4-fluorophenoxy)piperidine (104 mg, 0.45 mmol) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 80 mg (34%). LC/MS purity: UV/MS 99/84.

[0405] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.14 (dt, J = 8.0 and 0.6 Hz ₃ IH), 7.88 (s, IH), 7.43 (dt, J = 8.4 and 1.0 Hz, IH), 7.37-7.35 (m, 1H),7.26-7.16 (m, 5H), 6.96-6.92 (m, 2H), 6.85-6.82 (m, 2H), 4.53 (s, 2H), 4.21-4.18 (m, 3H), 2.63-2.59 (m, 2H), 2.25 (t, J = 7.4 Hz, 2H), 2.21-2.13 (m, 2H), 1.98 (pentet, J= 7.4 Hz, 2H), 1.91-1.86 (m, 2H), 1.71-1.63 (m, 2H).

1 -(l-{3-r4-(2-chIoroE>henoxy)-l-piperidinvπpropyl)-l H-indol-3-yl)ethanone C627b

[0406] l-[l-(3-chloroρropyl)-lH-indol-3-yl]-ethanone (117 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and 4-(2- chlorophenoxy)piperidine (1 1 1 mg, 0.45 mmol) were weighed into a MW vial and dry MeCN (2 raL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 181 mg (98%). LC/MS purity: UV/MS 99/95.

[0407] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.28 (s, IH), 8.24-8.22 (m, IH) ₅ .7.59-7.57 (m, IH), 7.35 (dd, J= 8.0 and 1.6 Hz, IH), 7.31 -7.21 (m, 3H), 7.12 (dd, J- 8.0 and 1.6 Hz, IH), 6.95 (dt, J = 7.2 and 1.2 Hz, IH), 4.73.4.69 (m, IH), 4.39 (t, J= 7.2 Hz, 2H), 3.36-3.17 (m, 6H), 2.51 (s, 3H) ₃ 2.40-2.36 (m, 2H) ₅ 2.20-2.05 (m, 4H).

l-{l-f3-f6-methoxy-L3λ9-tetrahvdro-2H-β-carbolin-2-yl)p ropyll-lH-indol-3-vUethanone C901b

[0408] l -[l -(3-chloropropyl)-lH-indol-3-yl]-ethanone (117 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and 6-methoxy- 1,2,3,4-tetrahydro-β-carboline (91 mg, 0.45 mmoJ) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 66 mg (37%). LC/MS purity: UV/MS 97/58.

[0409] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.25-8.23 (m, I H), 8.10 (s, IH), 7.47 (d, J = 8.4 Hz, IH), 7.28-7.19 (m, 2H) ₅ 7.14 (d, J= 8.8 Hz, IH), 6.87 (d, J= 2.4 Hz, IH), 6.70 (dd, J= 8.4 and 2.4 Hz, IH), 4.26 (t, J = 6.8 Hz, 2H), 3.76 (s, 3H), 3.69 (s, 2H) ₅ 2.88 (t, J = 6.0

Hz ₅ 2H), 2.76 (t, J = 6.0 Hz, 2H), 2.64 (t, J= 7.9 Hz, 2H), 2.43 (s, 3H) ₅ 2.15 (pentet, J= 7.9 Hz, 2H).

l-fl-Oα -[3-r4-chlorophenoxy)-8-azabicvclol ^' 3.2.noct-8-yl ^' |propyU-lH-indol-3-yl)ethanone C390b

[0410] l-[l-(3-chloropropyl)-lH-indol-3-yl]-ethanone (117 mg, 0.5 mmol), cesium carbonate (325 mg, 1 mmol), potassium iodide (83 mg, 0.5 mmol) and 3α-(4- chlorophenoxy)-8-azabicyclo[3.2.1]octane (106 mg, 0.45 mmol) were weighed into a MW vial and dry MeCN (2 mL) was added. The vial was capped and heated in the MW at 120 ⁰ C for 20 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-5 % MeOH in DCM. Yield: 90 mg (46%). LC/MS purity: UV/MS 99/96.

[0411] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.39-8.36 (m, I H), 7.81 (s, I H), 7.42-7.40 (m, IH), 7.30-7.21 (m, 4H), 6.76-6.73 (m, 2H), 4.50 (t, J= 5.6 Hz, 2H), 4.32 (t, J= 6.6 Hz, 2H), 3.13-3.12 (m, 2H), 2.52 (s, 3H), 2.29 (t, J= 6.6 Hz, 2H), 2.13-1.85 (m, 10 H).

[0412] ¹³ C NMR (100 MHz, CDCl ₃ ) δ: 193.1, 156.2, 137.1, 135.5, 129.7, 126.6, 125.5, 123.3, 122.8, 122.7, 117.2, 116.9, 110.1, 70.5, 58.4, 48.7, 44.6, 35.8, 28.7, 27.8, 26.3.

l-d-G-('4-(Ben2θ[d1thiazol-2-vπpiperidin-l-yl ^N )propyl)-7-methoxy-l//-indol-3-yl)ethanone oxalate C669b

[0413] The title compound was synthesized according to TP 12 at 0.35 mmol scale using 2-(piperidin-4-yl)benzo[d]thiazole (153 mg, 0.70 mmol) and no triethylamine. This gave 90 mg (58%) of the free base.

[0414] ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.98 (m, 2H), 7.86 (d, IH, J = 8.0 Hz) ₅ 7.71 (s, IH), 7.45 (Di ₁ IH), ^" 7.35 (m, IH), 7.17 (t, IH ₃ J= 8 Hz), 6.71 (d, IH J = 7.8 Hz), 4.49 (t, 2H, J = 6.6 Hz), 3.94 (s, 3H), 3.13 (m, IH) ₅ 3.03 (m, 2H) ₃ 2.49 (s, 3H), 2.32 (t, 2H ₃ J = 6.8 Hz), 2.23- 1.98 (m, 8H). The title compound (89 mg) was isolated as white crystals. MS (ES ⁺ , M+l) = 448.

l-(l-(3-(4-( ^" 2-Chlorophenoxy)piperidin-l-yl)propylV7-methoxy-l//-indol-3- yl)ethanone oxalate C629b

[0415] The title compound was synthesized according to TP 12 at 0.35 mmol scale using 4-(2-chlorophenoxy)piperidine hydrochloride (174 mg, 0.70 mmol). This gave 105 mg (68%) of the free base.

[0416] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ 7.98 (d, IH, J = 8.0 Hz), 7.70 (s, IH) ₃ 7.37 (dd, IH, J= 7.8, 1.6 Hz) ₅ 7.20 (m, IH) ₅ 7.17 (t, IH ₅ J= 8 Hz), 6.95 (dd, IH ₅ J- 8.2, 1.4 Hz) ₅ 6.90 (dl, IH ₅ J= 7.4, 1.4 Hz) ₅ 6.71 (d, IH J= 7.8 Hz) ₅ 4.47 (I ₅ 2H, J- 6.4 Hz), 4.40 (m, IH) ₅ 3.94 (s, 3H), 2.73 (m, IH), 2.49 (s, 3H), 2.32 (m, 4H) ₅ 2.05 (m, 4H) ₅ 1.90 (m, 2H). The title compound (96 mg) was isolated as white crystals. MS (ES ⁺ , M+l) = 441.

l-d-('3-r4-('4-Chlorophenoxy)piperidin-l -yI)propyl ^' )-7-methoxy-l/f-indol-3-yl)ethanone oxalate C645b

[0417] The title compound was synthesized according to TPl 2 at 0.35 mmol scale using 4-(4-chlorophenoxy)piperidine (115 mg, 0.55 mmol). This gave 60 mg (39%) of the free base. ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ 7.97 (d, IH, J= 8.0 Hz), 7.70 (s, IH), 7.22 (m, 2H) ₅ 7.17 (t, IH ₅ J = 8 Hz), 6.82 (m, 2H), 6.71 (d, IH J= 7.8 Hz), 4.47 (t, 2H ₅ J= 6.4 Hz) ₅ 4.29 (m, IH) ₅ 3.94 (s, 3H) ₅ 2.71 (m, IH) ₅ 2.49 (s, 3H), 2.32 (m, 4H) ₅ 2.05 (m, 4H), 1.82 (m, 2H). The title compound (60 mg) was isolated as white crystals. MS (ES ⁺ , M+l) = 441.

1 -(I -(3-C3 α -(4-Chlorophenoxy)-8-azabicyclo[3.2.1 ]octan-8-yl)propyiy7-methoxy-lH-indol- 3-yl)ethanone oxalate C598b

[0418] The title compound was synthesized according to TP 12 at 0.35 mmol scale using 3-(4-chlorophenoxy)-8-azabicyclo[3.2.1]octane (166 mg, 0.7 mmol) and no triethylamine. This gave 115 mg (70%) of the free base.

[0419] ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ 7.97 (d, 1 H, J - 8.0 Hz), 7.70 (s, 1 H), 7.20 (m, 2H), 7.15 (t, I H, J = 8 Hz), 6.72 (m, 2H), 6.69 (d, IH J = 7.8 Hz), 4.49 (m 3H), 3.92 (s, 3H), 3.28 (m, 2H), 2.49 (s, 3H), 2.42 (t, 2H, J = 7.2 Hz), 2.21 (m, 2H), 2.10-1.87 (m, 8H). The title compound (58 mg) was isolated as white crystals. MS (ES ⁺ , M) = 467.

1 -(7-bromo- 1 -(3-(4-(4-chlorophenoxy)piperidin- 1 -yDpropylV 1 H-indol-3-yl)ethanone oxalate C468b

[0420] A 4 mL vial was charged with 1 -(7-bromo- l-(3-chloropropyl)-lH-indol-3- yl)ethanone (139 mg, 0.44 mmol), 4-(4-chlorophenoxy)piperidine (87 mg, 0.41 mmol), Cs ₂ CO ₃ (232 mg, 0.71 mmol), NaI (62 mg, 0.41 mmol) and CH ₃ CN (2 mL). The mixture was stirred at 50 ⁰ C overnight and then at 80 ⁰ C for 6 h. To the resulting suspension was added H ₂ O (1 mL), EtOAc (2 mL) and the organic layer was applied to a SCX ion exchange

column. The cartridge was washed with MeOH, and the crude product was eluded with NH ₃ (MeOH). The resulting crude amine was purified by flash chromatography (EtOAc — > EtOAc:MeOH 4: 1) to give the free base (62 mg, 31%). Oxalic acid (1.1 eq) dissolved in acetone (0.3 ml) was added to the clear oil dissolved in acetone (0.5 ml). The precipitant was filtered off and dried to yield 62 mg of the title compound as white crystals.

[0421] ¹ H NMR (400 MHz, CDCl ₃ ) (of free base) δ 8.43 (dd, J = 8.0, 1.1 Hz,

1H),~7.83 (s, IH), 7.45 (dd, J- 7.7, 1.0 Hz ₅ IH), 7.24-7.20 (m, 2H) ₅ 7.12-7.08 (m, IH) ₅ 6.84- 6.80 (m, 2H) ₃ 4.65 (t, J = 6.7 Hz, 2H), 4.32-4.26 (m, IH), 2.76-2.68 (m, 2H), 2.50 (s, 3H), 2.36-2.27 (m, 4H), 2.15-1.98 (m ₃ 4H) ₅ 1.89-1.79 (m, 2H).

[0422] ¹³ C NMR (100 MHz, CDCl ₃ ) (of free base) δ 192.4, 155.9, 138.4, 133.1 , 129.7, 129.4, 128.6, 125.7, 123.5, 122.1, 1 17.3, 1 16.3, 103.7, 72.7, 54.1, 50.3, 46.6, 30.7, 28.6, 27.5.

l-(3-(4-(benzofdlthiazol-2-vπpiperidin-l -yI)propyl)-N-isobutyl-7-methoxy-lH-indole-3- carboxamide C184b

[0423] l-(3-chloropropyl)-N-isobutyl-7-methoxy-l H-indole-3-carboxamide (25 mg, 0.08 mmol), potassium iodide (2 mg, 0.01 mmol), DIPEA (21 mg, 0.16 mmol) and 2- (piperidin-4-yl)benzo[d]thiazole (34 mg, 0.16 mmol) were weighed into a vial and dry DMF (1 mL) was added. The vial was sealed and heated on a shaker at 80 °C for 24 h. The reaction mixture was diluted with EtOAc and washed with MgSO ₄ (4% aq.), water and brine, dried over sodium sulphate, filtered and concentrated onto celite. The product was purified by flash chromatography 0-10 % MeOH in DCM. Yield: 31 mg (78%).

[0424] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.96 (d, J = 6.5 Hz, IH), 7.85 (d, J = 6.5 Hz, IH), 7.54 (s, IH), 7.49 (d, J = 8.0 Hz ₅ IH), 7.45 (t, J = 8.4 Hz, IH), 7.34 (t, J= 8.4 Hz, IH), 7.12 (t, J= 8.4 Hz, IH), 6.67 (d, J= 8.0 Hz ₅ IH), 4.45 (t, J= 6.8 Hz, 2H), 3.94 (s, 3H),

3.32 (t, J= 6.0 Hz, IH), 3.1 1-2.98 (m, 3H), 2.33 (t, J= 6.8 Hz, I H), 2.07-1.90 (m, 9H), 1.00 (d, J= 7.6 Hz, IH).

[0425] ¹³ C NMR (400 MHz, CDCl ₃ ) δ: 177.1 , 166.4, 154.2, 148.9, 135.7, 133.9, 128.9, 127.2, 127.0, 125.8, 123.7, 123.O ₃ 122.7, 1 13.6, 1 12.1, 104.2, 56.5, 56.2, 54.4, 49.1 , 47.9, 42.7, 33.6, 30.0, 29.9, 21.4.

1 -(7-methoxy-l-(3-(4-propoxypiperidin-l -yl)propyl)-lH-indol-3-yl)ethanone C730b

[0426] Prepared according to TP 12 from l-(l-(3-chloropropyl)-7-methoxy-lH- indol-3-yl)ethanone (199 mg. 0.75 mmol) and 4-propoxypiperidine (214 mg, 1.5 mmol). Yield of the title compound: 247 mg (89%).

[0427] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.97 (d, J = 8.0 Hz, IH), 7.694 (s, IH), 7.161 (t, J = 8.0 Hz, I H), 6.70 (d, J = 8.0 Hz, IH), 4.44 (t, J = 6.8 Hz, 2H), 3.92 (s, 3H), 3.396(t, J = 6.8 Hz, 2H), 3.31-3.26 (m, I H), 2.76-2.67 (m, 2H), 2.48 (s, 3H), 2.21 (t, J = 6.4Hz ₅ 2H), 2.09-2.89 (m, 6H), 1.65-1.55 (m, 4H), 0.92 (t, J= 7.2 Hz, 2H).

l-(7-methoxy-l -r3-r4-propoxypiperidin-l-yl ^* )propyl')-lH-indol-3-vπethanol C902

[0428] LiAlH ₄ (3.8 mg, 0.1 mmol) was weighed into a dry, argon flushed vial, dry THF (1 mL) was added, followed by l-(7-methoxy-l-(3-(4-propoxypiperidin-l-yl)propyl)- 1 H-indol-3-yl)ethanone (20 mg, 0.05 mmol) in THF (1 mL). The reaction mixture was left for 1 h at rt followed by 1 h at 80 ⁰ C. Quenched with water and NaOH (2 N) and extracted with EtOAc. The combined organic phases was dried over Na ₂ SO ₄ and concentrated in

vacuo. The product was purified by flash chromatography 0-2 % MeOH in DCM. Yield: 7 mg (50%).

[0429] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.32 (d, J = 7.2 Hz, IH) ₅ 7.01-6.97 (m, 2H), , 6.61 (d, J = 8.0 Hz, IH), 5.17 (q, J = 5.6 Hz, IH), 4.35 (t, J = 7.2 Hz, 2H), 3.90 (S, IH), 3.37 (t, J= 6.8 Hz, IH), 3.29-3.24 (m, IH), 2.74-2.70 (m, 2H), 2.26 (t, J= 6.8 Hz ₅ 2H), 2.14-1.86 (m, 8H), 1.64-1.54 (m, 6H) ₃ 0.90 (t, J= 7.2 Hz, 3H).

3-ethyl-7-methoxy-l-(3-(4-propoxypiperidin-l-yl)propyl> ;lH-indole C903

[0430] l-(7-methoxy-l-(3-(4-propoxypiperidin-l-yl)propyl)-lH-indol- 3- yl)ethanone (20 mg, 0.05 mmol) was taken up in DCM in an argon flushed vial and cooled on an ice bath before slowly adding TiCl ₄ (10 mg, 0.05 mmol, neat), after 10 min BH ₃ -NHMe ₂ (6 mg, 0.1 mmol) was added in DCM (1 mL) and the reaction mixture was allowed to warm to rt, left for an additional 2 h before the reaction was quenched with HCl (2N). The crude product was taken up in EtOAc and washed with water, dried over Na ₂ SO ₄ and concentrated in vacuo. The product was purified by prep TLC from 2 % MeOH in DCM. Yield: 0.9 mg (8%). UY/MS: 95/90.

N-r3-chlorobenzylV7-methoxy-l-(3-((lR.3r,5S)-3-(2-oxo-2-p henvlethvl>-8- azabicyclo[3.2.1]octan-8-yl)propyiyiH-indole-3-carboxarnide C221b

[0431] Prepared according to TP12 from N-(3-chlorobenzyl)-l -(3-chloropropyl)- 7-methoxy-lH-indole-3-carboxamide (98 mg. 0.25 mmol) and 2-((lR,3r,5S)-8-

azabicyclop^.lJoctan-S-yQ-l-phenylethanone (115 mg, 0.5 mmol). Yield of the title compound: 113 mg (77%).

[0432] ¹ H-NMR (400 MHz, CDCl ₃ ) δ: 7.91 - 7.89 (m, 2H), 7.72 (d, J = 0.8 Hz, IH), 7.64 (d, J = 8.0 Hz, IH), 7.57 - 7.53 (m, IH), 7.46 - 7.43 (m, 2H), 7.34 (s, IH), 7.26 - 7.19 (m, 3H), 7.10 (dt, J= 1.2 and 8.0 Hz, IH), 6.65 (d, J = 8.0 Hz, IH), 4.64 (d, J= 6.0 Hz, 2H), 4.47 (t, J= 6.8 Hz, 2H), 3.92 (s, 3H), 3.17 - 3.12 (m, 2H), 3.05 (d, J = 7.2 Hz, 2H), 2.56 - 2.49 (m, IH), 2.22 - 2.15 (m, 4H), 1.99 - 1.87 (m, 4H), 1.68 - 1.57 (m, 2H), 1.25 - 1.17 (m, 2H).

7-methoxy-N-r3-methylbenzyl)-l-r3-r( ^' lR,3r,5SV3-r2-oxo-2-phenvIethyl>-8- azabicyclo[3.2.1]octan-8-yl)propylHH-indole-3-carboxarnide C193b

[0433 j Prepared according to TPl 2 from l-(3-chloropropyl)-7-methoxy-N-(3- methyIbenzyl>lH-indole-3-carboxamide (98 mg. 0.25 mmol) and 2-((lR,3r,5S)-8- azabicyclo[3.2.1]octan-3-yl)-l-phenylethanone (115 mg, 0.5 mmol). Yield of the title compound: 111 mg (46%).

[0434] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.93 - 7.89 (m, 2H), 7.75 - 7.53 (m, 3H), 7.46 - 7.40 (m, 2H), 7.33 - 7.06 (m, 5H), 4.68 - 4.63 (m, 2H), 4.50 - 4.43 (m, 2H), 3.97 (s, 3H), 3.17 - 3.05 (m, 4H), 2.53 - 2.45 (m, IH), 2.33 (s, 3H), 2.27 - 2.15 (m, 4H), 1.98 - 1.90 (m, 4H), 1.67 - 1.60 (m, 2H), 1.22 - 1.17 (m, 2H).

[0435] ¹³ C NMR (400 MHz, CDCl ₃ ) δ: 200.3, 147.8, 138.9, 138.5, 133.3, 133.2, 132.8, 131.1, 129.0, 129.0, 128.8, 128.7, 128.7, 128.2, 126.3, 124.9, 122.1 , 113.1 , 103.4, 58.3, 55.5, 50.6, 50.6, 48.1, 46.9, 43.6, 35.1 , 30.2, 27.1, 23.9.

Synthesis of libraries

[0436] Alkyl halides (0.03 mmol/reaction) were dissolved in ^' DMF (0.5 mL/reaction). Secondary amines (0.06 mmol/reaction) and DIEA (0.06 mmol/reaction) were dissolved in DMF (0.3 mL/reaction). NaI (cat) was added to a microtiter plate. The microtiter plate was moved to liquid handler and the solutions containing alkyl halides and amines were dispensed. The microtiter plate was shaken at 80 ⁰ C for 22 hours. Volatile materials were then removed at reduced pressure. The remaining crude products were dissolved in DMF (0.32 mL) and filtered using a 96-position filter plate (0.8 mL, 0.4 micrometer) into microtiter plates. The crude products were purified by preparative LC/MS according to PP (analytical methods). Purity analyses of the purified products were performed according to AP (analytical methods).

[0437] The following compounds were prepared using the library procedure:

N-f3,4-dichlorobenzyI ^' )-7-isopropoxy-l -(3-(4-( ^" 3-phenoxypropyl)- 1 ,4-diazepan- 1 -yl)propyl> 1 H-indole-3-carboxamide COOl

[0438] Amount made: 1.6 mg. LCMS m/z 651 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -(3-C4-r2-f4-chloronaphthalen- 1 -yloxy)ethyl)piperazin- 1 -yQpropyD-N-f 3-fluorobenzvO-7- methoxy- 1 H-indole-3-carboxamide C002

[0439] Amount made: 3.3 mg. LCMS m/z 629 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3,4-dichlorobenzyπ-7-ethyl- 1 -( ^r 3-(4-(2-phenoxyethyl)pipera2in- 1 -yl)proρyl> 1 H-indole-3- carboxamide C003

[0440] Amount made: 3.3 mg. LCMS m/z 593 [M+H] ⁺ , purity (UV/MS) 100/90.

carboxamide C004

[0441] Amount made: 6.3 mg. LCMS m/z 591 [M+H] ⁺ , purity (UV/MS) 96/80.

N-Q^-dichlorobenzvD-y-ethyl-l-O^-^-fluorobenzvD-l λ-diazepan-l-vDpropyD-lH- indole-3-carboxamide C005

[0442] Amount made: 5.6 mg. LCMS m/z 595 [M+H] ⁺ , purity (UV/MS) 85/70.

l-O-fπRJr^SVS-r∑-rS^-dichlorophenvD-σ-oxoethylVS-azabicv clors^.noctan-8- y l)propyiy7-isopropoxy-N-( ^' 3-methylbenzyl)- 1 H-indole-3-carboxamide CQQ6

[0443] Amount made: 1.1 mg. LCMS m/z 660 [M+H] ⁺ , purity (UV/MS) 100/90.

l -O-CπRJr^SVS-α-^-chlorophenvn^-oxoethvn-8-azabicvclorS^.ll octan-S-vnpropylV?- isopropoxy-N-(3-methylbenzy1)-l H-indole-3-carboxamide C007

[0444] Amount made: 5.0 mg. LCMS m/z 626 [M+H] ⁺ , purity (UV/MS) 99/80.

7-isopropoxy-N-(3-methylbenzylVl -(3-(πR.3r,5S)-3-(2-oxo-2-(pyridin-2-vnethyl)-8- azabicyclof3.2.πoctan-8-yl ^* )propyl)-l H-indole-3-carboxamide C008

[0445] Amount made: 1.8 mg. LCMS m/z 593 [M+HJ ⁺ , purity (UV/MS) 100/70.

l -(3-(4-C2-chloro-6-fluorobenzyl)-L4-diazepan-l-vπpropyl)-N- (3,4-dichlorobenzvπ-7-ethyl- 1 H-indole-3-carboxamide C009

[0446] Amount made: 7.3 mg. LCMS m/z 629 [M+H] ⁺ , purity (UV/MS) 98/80.

l-C3-(nR,3r,5SV3-(2-(3-chloro-4-fluorophenylV2-oxoethylV8 -a2abicvclo[3.2.noctan-8- yOproρyl>7-isopropoxy-N-(3-methylbenzyiyi H-indole-3-carboxamide COlO

[0447] Amount made: 3.3 mg. LCMS m/z 644 [M+H] ⁺ , purity (UV/MS) 97/70.

7-isopropoxy-N-(3-methylbenzyl)-l-(3-(4-( ^' 2-phenoxyethyl ^' )piperidin-l-yπpropyiyi H-indole- 3-carboxamide COIl

[0448] Amount made: 0.9 mg. LCMS m/z 568 [M+H] ⁺ , purity (UV/MS) 73/60.

1 -(3-(4-(2-(4-fluorophenoxy)ethyl ^: )-l ,4-diazepan-l -yπpropyl>7-isopropoxy-N-(3- methylbenzy I)- 1 H-indole-3 -carboxamide COl 2

[0449] Amount made: 1.4 mg. LCMS m/z 601 [M+H] ⁺ , purity (UV/MS) 100/100.

l-r3-fπS.4SV5-(2-( ^" 4-fluorophenoxy ^> >ethylV2.5-diazabicvclor2.2.21octan-2-vnpropylV7- isopropoxy-N-O-methylbenzylVl H-indole-3-carboxamide C013

[0450] Amount made: 6.0 mg. LCMS m/z 613 [M+H] ⁺ , purity (UV/MS) 100/90.

N-f3.4-dichlorobenzylVl-(3-(dR.SSV3-f2-f4-fluorophenoxy ^' >ethyl>-3.8- diazabicyclop^.lfoctan-δ-yOpropyiyT-isopropoxy-l H-indole-3-carboxamide CO 14

[0451] Amount made: 2.6 mg. LCMS m/z 667 [M+H] ⁺ , purity (UV/MS) 90/70.

N-benzyI-7-ethyl- 1 -(3-(4-(2-phenoxyethyl')-h4-dia2epan-l -vDpropylV 1 H-indole-3- carboxamide COl 5

[0452] Amount made: 1.5 mg. LCMS m/z 539 [M+H] ⁺ , purity (UV/MS) 100/100.

N-(3.4-dichlorobenzylVl-(3-(αR,3r.5SV3-f2-r3.4-dichlorophen vn-2-oxoethvn-8- azabicyclor3.2.1]octan-8-yl')propyl ^' )-7-isopropoxy-lH-indole-3-carboxamide C016

[0453] Amount made: 2.3 mg. LCMS m/z 714 [M+H] ⁺ , purity (UV/MS) 96/60.

l-f3-f(lR.3r.5SV3-(2-(4-chlorophenylV2-oxoethvn-8-a2abicy clor3.2.noctan-8-yl')ρropylVN- (3,4-dichlorobenzyl)-7-isopropoxy-lH-indole-3-carboxarnide C017

[0454] Amount made: 2.1 mg. LCMS m/z 680 [M+H] ⁺ , purity (UV/MS) 98/70.

l-r3-f(lR,3r,5S)-3-f2-G-chloro-4-fluorophenylV2-oxoethylV 8-azabicvclor3.2.noctan-8- y0propyl>-N-(3,4-dichlorobenzyl>7-isopropoxy-l H-indole-3-carboxamide C018

[0455] Amount made: 6.6 mg. LCMS m/z 698 [M+H] ⁺ , purity (UV/MS) 87/70.

N-(3 ,4-diehlorobenzyl)-7-isopropoxy- 1 -(3-(4-(2-phenoxyethy Dpiperidin- 1 -vDpropy IV 1 H- indole-3-carboxamide C019

[0456] Amount made: 3.9 mg. LCMS m/z 622 [M+H]\ purity (UV/MS) 85/50.

l-(3-(4-(2-(4-chloronaphthaIen-l-yloxy)ethyl ^' )piperazin-l-yπpropyl>-N-( ^' 3,4-dichlorobenzvπ- 7-ethyl-l H-indole-3-carboxamide C020

[0457] Amount made: 6.8 mg. LCMS m/z 677 [M+H] ⁺ , purity (UV/MS) 100/80.

N-r3,4-dichlorobenzylVl-C3-(4-C2-( ^' 4-fluorophenoxy ^' )ethyl>-l,4-dia2epan-l-yl ^* )propyl>-7- isopropoxy-1 H-indole-3-carboxamide C021

[0458] Amount made: 3.2 mg. LCMS m/z 655 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3.4-dichlorobenzvπ-7-isopropoxy-l-(3-(4-( ^/ 2-phenoxyethyl>-l ,4-dia2epan-l-yl)propyl')- 1 H-indole-3-carboxamide C022

[0459] Amount made: 1.1 mg. LCMS m/z 637 [M-HH] ⁺ , purity (UV/MS) 100/100.

i-f3-fdS,4SV5-r2-C4-fluorophenoxy')ethylV2.5-diazabicvclo r2.2.2]octan-2-vnpropylV7- methoxy-N-C3-methylbenzylVl H-indole-3-carboxamide C023

[0460] Amount made: 2.5 mg. LCMS m/z 585 [M+H] ⁺ , purity (UV/MS) 100/90.

l-f3-fnR,5S)-3-(2-(4-fluorophenoxv)ethvl)-3,8-diazabicvcl or3.2.11octan-8-vnpropylV7- methoxy-N-(3-rnethylbenzyiyi H-indole-3-carboxamide C024

[0461] Amount made: 2.1 mg. LCMS m/z 585 [M-HH] ⁺ , purity (UV/MS) 100/80.

N-f 3 ,4-dichlorobenzvD-7-ethyl-l -f 3 -(4-(3-phenoxypropyl)piperazin- 1 -yPpropylV 1 H-indole- 3-carboxamide C025

[0462] Amount made: 8.2 mg. LCMS m/z 607 [M-HH] ⁺ , purity (UV/MS) 99/50.

7-methoxy-N-(3-methylbenzyl>-l-(3-(4-f3-phenoxypropyl& gt;l ,4-diazepan- l-yπpropylVlH- indole-3-carboxamide C026

[0463] Amount made: 1.2 mg. LCMS m/z 569 [M+H] ⁺ , purity (UV/MS) 98/90.

l-f3-(TlR.3r.5SV3-(2-r4-chlorophenylV2-oxoethylV8-a2abicy clor3.2.11octan-8-vnpropylV7- methoxy-N-(3-rnethylbenzyiyi H-indole-3-carboxamide C027

[0464] Amount made: 3.1 mg. LCMS m/z 598 [M+H] ⁺ ₅ purity (UV/MS) 99/70.

N-(3.4-dichlorobenzyn-l-(3-((lS,4SV5-r2-(4-fluorophenoxy& gt;ethyl')-2,5- diazabicyclof2.2.21octan-2-yl)propyl)-7-isopropoxy-l H-indole-3-carboxamide C028

[0465] Amount made: 3.2 mg. LCMS m/z 667 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -f 3 -(4-f4-fluorobenzyD- 1 ,4-diazepari- 1 -yDpropylV 7-methoxy-N-(2-methy Ibenzyl)- 1 H- indole-3-carboxamide C029

[0466] . Amount made: 0.3 mg. LCMS m/z 543 [M+H] ⁺ , purity (UV/MS) 99/90.

l-r3-(4-(2-( ^' 4-chlorophenoxy)ethyl)piperazin-l-yl)propylV7-methoxy-N-(2-m ethylbenzylV lH-indole-3-carboxamide C030

[0467] Amount made: 6.3 mg. LCMS m/z 575 [M+H] ⁺ , purity (UY/MS) 100/100.

N-f3,4-dichlorobenzvn-7-ethvM-π-(πS.4S)-5-(2-f4-fluorop henoxy)ethviV2,5- diazabicvcIof2.2.2]octan-2-yl)propyl)-lH-indole-3-carboxamid e C031

[0468] Amount made: 1.6 mg. LCMS m/z 637 [M+H] ⁺ , purity (UV/MS) 100/100.

N-π,4-dichlorobenzyn-7-ethyl-l-r3-(flR,5SV3-r2-r4-fluoro phenoxy)ethylV3,8- diazabicyclor3.2.1]octan-8-yl)propyl>lH-indole-3-carboxar nide C032

[0469] Amount made: 2.6 mg. LCMS m/z 637 [MH-H] ⁺ , purity (UV/MS) 100/100.

7-isopropoxy-N-f3-methylbenzyl>l-(3-(4-f3-phenoxypropy D-l ,4-diazepan-l -yQpropylη H- indole-3-carboxamide C033

[0470] Amount made: 2.5 mg. LCMS m/z 597 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-rπR.3r.5SV3-r2-r4-chlorophenvn-2-oxoethvn-8-azabicv clor3.2.noctan-8-ynpropylVN- (3,4-dichlorobenzyl)-7-ethyl-lH-indole-3-carboxamide C034

[0471] Amount made: 4.0 mg. LCMS m/z 650 [M+H] ⁺ , purity (UV/MS) 100/80.

N-ben2yl-l-(3-π-benzylpyrrolidin-3-ylamino)propyl>-7- ethyl-lH-indole-3-carboxamide C035

[0472] Amount made: 5.2 mg. LCMS m/z 495 [M+H] ⁺ , purity (UV/MS) 98/60.

N-(3,4-dichloroben2yl)-7-ethyl-l-(3-(4-( ^' 2-phenoxyethyl)piperidin-l-yπpropyl ^' )-lH-indole-3- carboxamide C036

[0473] Amount made: 4.9 mg. LCMS m/z 592 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -f 3-(4-f 2-f diisopropylarnino)ethyl)piperazin- 1 -yl)propyl>7-methoxy-N-(2-methylbenzyl> lH-indole-3-carboxamide C037

[0474] Amount made: 8.3 mg. LCMS m/z 548 [M+H] ⁺ , purity (UV/MS) 98/80.

N-( ^" 3,4-dichlorobenzyl)-7-ethyl-l -(3-(4-(2-(4-fIuorophenoxy)ethylV 1 ,4-diazepan-l - yPpropylV 1 H-indole-3-carboxamide C038

[0475] Amount made: 5.2 mg. LCMS m/z 625. [M+H] ⁺ ₅ purity (UV/MS) 97/80.

N-f 3 ,4-dich]orobenzyIV 7-ethy 1- 1 -f 3-(4-(2-phenoxyethy IV 1 ,4-diazepan- 1 -vQpropylV 1 H- indole-3-carboxamide C039

[0476] Amount made: 2.0 mg. LCMS m/z 607 [M+H] ⁺ , purity (UV/MS) 100/100.

7-methoχy-N-r2-methylbenzyl)-l-(3-(4-f2-moφholino-2-oxo ethyl)piperazin-l -yl)propylV 1 H-indole-3-carboxamide C040

[0477] Amount made: 5.1 mg. LCMS m/z 548 [M+H] ⁺ , purity (UV/MS) 100/80.

l-π-rπR,SS)-3-r2-f4-fluorophenoχy)ethylV3.8-diazabicyc lor3.2.noctan-8-vnpropylV7- isopropoxy-N-G-methyl benzyl Vl H-indole-3-carboxamide C041

[0478] Amount made: 3.2 mg. LCMS m/z 613 [M+H] ⁺ , purity (UV/MS) 85/50.

7-methoxy-N-(2-methylbenzyiy 1 -(3-(4-phenethyl-l ,4-diazepan- 1 -yOpropylVl H-indole-3- carboxamide C042

[0479] Amount made: 5.9 mg. LCMS m/z 539 [M+H] ⁺ , purity (UV/MS) 99/70.

7-methoxy-N-r3-methylbenzylVl-(3-( ^' 4-(2-phenoxyethyl)piperidin-l-yl ^' )propylVlH-indole-3- carboxamide C043

[0480] Amount made: 1.9 mg. LCMS m/z 540 [M+H] ⁺ , purity (UV/MS) 100/70.

N-benzyl-7-ethyl-l-π-rπ S,4SV5-r2-r4-fluorophenoxy Methyl V2.5-diazabicvclor2.2.2]octan-2- yPpropyiy 1 H-indole-3-carboxamide C044

[0481] Amount made: 1.5 mg. LCMS m/z 569 [M+H] ⁺ , purity (UV/MS) 100/100.

N-benzyl-y-ethyl-l-π-fπR.SSVS-Q-^-fluorophenoxy'lethvn- S.δ-diazabicvclop.Z.lloctan- δ-yDpropyiyi H-indole-3-carboxamide C045

[0482] Amount made: 4.2 mg. LCMS m/z 569 [IVH-H] ⁺ , purity (UV/MS) 100/100.

1 -G-(4-r2-chloro-6-fluorobenzyl ^' )- 1 ,4-diazepan-l -vπpropylV7-methoxy-N-r2-methylbenzyl>- lH-indole-3-carboxamide C046

[0483] Amount made: 4.1 mg. LCMS m/z 577 [M+H] ⁺ , purity (UV/MS) 98/70.

1 -(3-(4-(2-chloro-6-fluorobenzyl ^' )- 1 ,4-diazepan-l -yl)propylVN-( ^' 3-fluorobenzλ ^f lV7-methoxy- 1 H-indole-3-carboxamide C047

[0484] Amount made: 4.1 mg. LCMS m/z 581 [M+H] ⁺ , purity (UV/MS) 97/70.

7-methoxy-N-(2-methylbenzylVl -(3-(4-(3-phenoxypropyπpiρerazin- 1 -vDpropylVl H-indole- 3-carboxamide C048

[0485] Amount made: 3.1 mg. LCMS m/z 555 [M+H] ⁺ , purity (UV/MS) 100/90.

7-methoxy-N-r2-methylbenzyl)-l-r3-r4-phenethylpiperazin-l -yl')propylVlH-indole-3- carboxamide C049

[0486] Amount made: 6.2 mg. LCMS m/z 525 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-(l-ben2ylpyrrolidin-3-ylamino)propyl>-N-r3,4-dich lorobenzyl)-7-ethyl-lH-indole-3- carboxamide C050

[0487] Amount made: 1.0 mg. LCMS m/z 563 [M+H] ⁺ , purity (UV/MS) 97/80.

N-benzyl-7-ethyl- 1 -f3-(4-(2-phenoxyethyl ^* )piperidin- 1 -vDpropylV 1 H-indole-3-carboxamide COSl

[0488] Amount made: 1.8 mg. LCMS m/z 524 [M+H] ⁺ , purity (UV/MS) 100/100.

N-benzv 1-7-ethy 1- 1 -f 3-( 4-(2-(4-fluorophenoxy')ethylV 1.4-diazepan- 1 -y HpropylV 1 H-indole-3- carboxamide C052

[0489] Amount made: 4.8 mg. LCMS m/z 557 [M+H] ⁺ , purity (UV/MS) 96/80.

N-(3-fluoroben2yl)-l-(3-(4-( ^' 4-fluorobenzvπ-1.4-diazepan-l-yl)propyl ^' >-7-methoxy-lH- indole-3-carboxamide C053

[0490] Amount made: 1.0 mg. LCMS m/z 547 [M+H] ⁺ , purity (UV/MS) 99/90.

N-(3,4-dichlorobenzyπ-l-r3-f4-( ^' 2-fdiisopropylamino)ethyl)piperazin-l-yπpropylV7-ethyl- lH-indole-3-carboxamide C054

[0491] Amount made: 7.2 mg. LCMS m/z 600 [M+H] ⁺ , purity (UV/MS) 100/90.

N-f 3.4-dichlorobenzyl)-7-ethyl- 1 -( ^" 3-(4-(2-morpholino-2-oxoethyDpiperazin- 1 -vDpropylV 1 H- indole-3-carboxamide C055

[0492] Amount made: 5.9 mg. LCMS m/z 600 [M+H] ⁺ , purity (UV/MS) 100/100.

7-methoxy-N-C2--rnethylbenzy IV 1 -(3-f4-(2-phenoxyethyl)piperazin- 1 -y Dpropy 1 V 1 H-indole-3- carboxamide CQ56

[0493] Amount made: 1.9 mg. LCMS m/z 541 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(3-(4-(2-(diisopropylamino ^' )ethyl)piperazin-l-yl)propyl ^' )-7-isopropoxy-N-(3-methylben2yl)- 1 H-indole-3-carboxamide C057

[0494] Amount made: 7.1 mg. LCMS m/z 576 [M+H] ⁺ , purity (UV/MS) 98/70.

N-(3,4-dichlorobenzyl)-7-isopropoxy-l -(3-(4-phenethyl- 1 ,4-diazepan-l -vDpropyl)- 1 H- indole-3-carboxamide C058

[0495] Amount made: 5.3 mg. LCMS m/z 621 [M+H] ⁺ , purity (UV/MS) 99/80.

N-(3,4-dichlorobenzyπ-7-isopropoxy-l-( ^' 3-('4-(2-phenoxyethyl)piperazin-l-yl)propyl)-lH- indole-3-carboxamide C059

[0496] Amount made: 4.0 mg. LCMS m/z 623 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3,4-dichlorobenzyl)-7-isopropoxy-l-( ^' 3-r4-r2-moφholino-2-oxoethyl ^' )piperazin-l- yl)propyl)-l H-indole-3-carboxamide C060

[0497] Amount made: 2.3 mg. LCMS m/z 630 [M-HH] ⁺ , purity (UV/MS) 100/90.

N-f3,4-dichlorobenzylVl-('3-(4-f2-( ^' diisopropylamino ^' )ethyI)piperazin-l-vπpropyl ^' )-7- isopropoxy-1 H-indole-3-carboxamide C061

[0498] Amount made: 3.9 mg. LCMS m/z 630 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -(3-(4-(2-(4-chlorophenoxy)ethv0piperazin-l -yl)propyl>-N-(3.4-dichlorobenzyl>7- isopropoxy-1 H-indole-3-carboxamide C062

[0499] Amount made: 6.4 mg. LCMS m/z 657 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -(3-( 1 -benzylpyrroUdin-3-ylamino ^' )propyl>-N-r3,4-dichlorobenzylV7-isoproDoxy-l H-indole- 3-carboxamide C063

[0500] Amount made: 2.6 mg. LCMS m/z 593 [M+H] ⁺ , purity (UV/MS) 94/80.

1 -(3-CdJhVdTO- lH-pyridof L2-a1pyrazin-2(6H JR8R9H,9aH)-v i)propylV7-isopropoxy-N-(3- methylbenzylVl H-indole-3-carboxamide C064

[0501] Amount made: 2.9 mg. LCMS m/z 503 [M+H] ⁺ , purity (UV/MS) 100/100.

7-isopropoxy-N-(3-methylbenzylVl-(3-(4-phenethylpiperazin -l-yl)propylVlH-indole-3- carboxamide C065

[0502] Amount made: 4.6 mg. LCMS m/z 553 [M+H) ⁺ , purity (UV/MS) 85/60.

7-isopropoxy-N-(3-methylbenzylVl-(3-(4-(3-phenoxvpropyl ^' )piperazin-l-vπpropyl>-lH- indole-3-carboxamide C066

[0503] Amount made: 3.0 mg. LCMS m/z 583 [M+H] ⁺ , purity (UV/MS) 99/70.

l-(3-(4-(2-(4-chloronaphthalen-l-yloxy ^' )ethyl)piperazin-l-yl)propyl>7-isopropoxv-N-(3- methy Ibenzy IV 1 H-indol e-3 -carboxamide CQ67

[0504] Amount made: 2.9 mg. LCMS m/z 653 [M+H] ⁺ , purity (UV/MS) 100/90.

7-isopropoxy-N-(3-methylbenzyl> 1 -(3-(4-phenethyl-l ,4-diazepan-l -vDpropylVl H-indole-3- carboxamide C068

[0505] Amount made: 1.5 mg. LCMS m/z 567 [M+H]\ purity (UV/MS) 99/70.

7-methoxy-N-f3-methylbenzylVl-r3-r(lR,3r,5S)-3-(2-oxo-2-Cpyr idin-2-yl)ethylV8- azabicvclo| ^" 3.2. l ^" joctan-8-yl)propyl)-lH-indole-3-carboxamide C069

[0506] Amount made: 1.3 mg. LCMS m/z 565 [M+H]\ purity (U V/MS) 97/80.

7-isopropoxy-N-('3-methylbenzyl)-l-( ^/ 3-( ^' 4-C2-moφholino-2-oxoethyl)piperazin-l-yl)propyl ^' )- lH-indole-3-carboxaniide C070

[0507] Amount made: 5.8 mg. LCMS m/z 576 [M+H] ⁺ ₃ purity (UV/MS) 100/80.

N-(3.4-dichlorobenzylV7-isopropoxy-l-(3-( ^' 4-phenethylpiperazin-l-vπpropylVlH-indole-3- carboxamide C071

[0508] Amount made: 3.6 mg. LCMS m/z 607 [M+H] ⁺ , purity (UV/MS) 100/80.

l-r3-( ^" 4-(2-(4-chlorophenoxy)ethyl)piperazin-l-yl)propyl>-7-isop ropoxy-N-(3-methylbenzyl)- 1 H-indole-3-carboxamide C072

[0509] Amount made: 3.1 mg. LCMS m/z 603 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-(l -benzylρyrrolidin-3-ylamino)propyl>-7-isopropoxy-N-(3-me thylbenzyl')-lH-indole-3- carboxamide C073

[0510] Amount made: 3.5 mg. LCMS m/z 539 [M+H] ⁺ , purity (UV/MS) 98/80.

N-benzyl-l-G-rdihvdro-lH-pyridori.2-a1pyrazin-2f6H.7H.8H, 9H.9aH>yl)propylV7-ethyl- 1 H-indole-3-carboxamide C074

[0511] Amount made: 3.9 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 100/100.

N-benzyl-7-ethyl- 1 -f3-f4-(3-phenoxypropyl)piperazin- 1 -vDpropyl)- 1 H-indole-3-carboxamide C075

[0512] Amount made: 2.2 mg. LCMS m/z 539 [M+H] ⁺ , purity (UV/MS) 100/100.

l-f3-(4-(2-(diisopropylamino)ethyπpiperazin-l-yl)propyl) -N-(3-fluorobenzyl)-7-methoxy- 1 H-indole-3-carboxamide C076

[0513] Amount made: 9.0 mg. LCMS m/z 552 [M+H] ⁺ , purity (UV/MS) 81 /60.

N-benzyl-1 -(3-(4-(2-chloro-6-fluorobenzyl>-l ,4-diazepan-l -yl)propyl)-7-ethyl-l H-indoIe-3- carboxamide C077

[0514] Amount made: 3.6 mg. LCMS m/z 561 [M+H] ⁺ , purity (UV/MS) 100/90.

N-benzyl-7-ethyl- 1 -(3 -(4-(4-fluorobenzy 0- 1 ,4-diazepan- 1 -y Opropy I)- 1 H-indole-3- carboxamide C078

[0515] Amount made: 5.1 mg. LCMS m/z 527 [M+H] ⁺ , purity (UV/MS) 90/60.

N-(3-fluorobenzyl)-7-methoxy- 1 -(3-(4-f2-morpholino-2-oxoethyl)piperazin-l -yDpropylV 1 H- indoIe-3-carboxamide C079

[0516] Amount made: 9.4 mg. LCMS m/z 552 [M+H] ⁺ , purity (UV/MS) 98/80.

N-(3-fϊuorobenzyl ^' )-7-methoxy-l-r3-r4-r2-phenoxyethyl)piperazin-l-vI)propylVlH -indole-3- carboxamide C080

[0517] Amount made: 6.3 mg. LCMS m/z 545 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3-fluorobenzy l)-7-methoxy- 1 -(3-f 4-phenethyl- 1.4-diazepan- 1 -vnpropylV 1 H-indole-3- carboxamide C081

[0518] . Amount made: 6.0 mg. LCMS m/z 543 [M+H] ⁺ , purity (UV/MS) 98/80.

N-benzyl-1 -(3-(4-(2-(diisopropylamino)ethv0piperazin-l -yl ^* )propyl>7-ethyl-l H-indole-3- carboxamide C082

[0519] Amount made: 6.7 mg. LCMS m/z 532 [M+H] ⁺ , purity (UV/MS) 99/80.

N-benzyl-1 -(3-(4-( ^" 2-r4-chlorophenoxy)ethvπpiperazin-l-yl)propyl>-7-ethyl-l H-indole-3- carboxamide C083

[0520] Amount made: 8.9 mg. LCMS m/z 559 [M+H] ⁺ , purity (UV/MS) 100/90.

7-isopropoxy-N-( ^' 3-methylbenzyl ^' )-l-(3-( ^' 4-r2-phenoxyethvπpiperazin-l-yl ^' )propyl)-l H- indole-3-carboxamide C084

[0521 ] Amount made: 4.8 mg. LCMS m/z 569 [M+H] ⁺ , purity (UV/MS) 100/90.

N-G ,4-dichlorobenzy P-7-methoxy- 1 -(3 -(4-phenethy lpiperazin- 1 -y DpropylV 1 H-indole-3 - carboxamide C085

[0522] Amount made: 2.1 mg. LCMS m/z 579 [M+H] ⁺ , purity (UV/MS) 100/100.

N-O^-dichlorobenzyiyV-ethyl-l-O-^-O-phenoxypropylV 1, ^diazepan-l-yPpropyiyi H- indole-3-carboxamide C086

[0523] Amount made: 1.8 mg. LCMS m/z 621 [M+H] ⁺ , purity (UV/MS) 100/90.

l -(3-C4.(2-(4-fluorophenoxy ^' )ethyl ^' )-1.4-diazepan-l-yl ^' )propyl>-7-methoxy-N-( ^' 3- methylbenzylVlH-indole-3-carboxamide C087

[0524] Amount made: 2.4 mg. LCMS m/z 573 [M+H] ⁺ , purity (UV/MS) 100/90.

7-methoxy-N-( ^' 3-methylbenzyl ^* )-l-(3-(4-(2-phenoxyethyl ^' )-l,4-diazepan-l-yl)propyl>-lH- indole-3 -carboxamide C088

[0525] Amount made: 1.0 mg. LCMS m/z 555 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3-(I -benzylpyrrolidin-3-ylamino)propyl>N-(3,4-dichlorobenzyl) -7-methoxy-l H-indole-3- carboxamide C089

[0526] Amount made: 3.4 mg. LCMS m/z 565 [M+H] ⁺ , purity (UV/MS) 99/80.

1 -(3 -(4-(2-(4-chlorophenoxy)ethyl)piperazin- 1 -v0propyl)-N-(3.4-dichlorobenzylV 7-methoxy- 1 H-indole-3-carboxamide C090

[0527] Amount made: 8.1 mg. LCMS m/z 629 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3,4-dichlorobenzylVl-(3-(4-(2-(diisopropylamino)ethyπpip erazin-l-yl ^' )propylV7- methoxy- 1 H-indole-3-carboxamide C091

[0528] Amount made: 6.9 mg. LCMS m/z 602 [M+H] ⁺ , purity (UV/MS) 99/90.

N-(3,4-dichlorobenzvπ-7-methoxy-l-(3-(4-(2-mθφholino-2-ox oethyl ^' )piperazin-l-yl ^' )propyl ^' )- 1 H-indole-3-carboxamide C092

[0529] Amount made: 8.5 mg. LCMS m/z 602 [M+H] ⁺ , purity (UV/MS) 100/80.

N-(3 ,4-dichlorobenzyl)-7-methoxy- 1 -(3-f 4-f2-phenoxyethyl)piperazin- 1 -ylipropylV 1 H- indoIe-3-carboxamide C093

[0530] Amount made: 6.9 mg. LCMS m/z 595 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3,4-dichlorobenzvD-7-methoxy- 1 -f3-f4-ph.enetb.yl- 1 ,4-diazepan- 1 -vDpropyl V 1 H-indole-3 - carboxamide C094

[0531] Amount made: 8.0 mg. LCMS m/z 593 [M+H] ⁺ , purity (UV/MS) 99/80.

N-(3,4-dichlorobenzyl)-l-( ^' 3-(4-r4-fluorobenzyl)-l ,4-diazepan-l-yl)propyl ^' )-7-methoxy-l H- indole-3 -carboxamide C095

[0532] Amount made: 1.7 mg. LCMS m/z 597 [M+H] ⁺ , purity (UV/MS) 99/90.

l-r3-(4-(2-chloro-6-fluorobenzyπ-1.4-diazepan-l-yl)propy l)-N-(3,4-dich]orobenzyI)-7- methoxy-1 H-indole-3 -carboxamide C096

[0533] Amount made: 4.7 mg. LCMS m/z 631 [M+H] ⁺ , purity (UV/MS) 89/60.

l-(3-(4-(2-(4-chloronaphthalen-l-yloxy ^' )ethyπpiperazin-l-yl)propyl ^' )-N-( ^' 3,4-dichlorobenzyπ- 7-methoxy- 1 H-indoIe-3-carboxamide C097

[0534] Amount made: 4.0 mg. LCMS m/z 679 [M+H] ⁺ , purity (UV/MS) 100/90.

l-C3-(4-( ^' 2-(4-chloronaphthalen-l-yloxy)ethyπpiperazin-l-yπpropyl)-N -(3,4-dichlorobenzyl)- 7-isopropoxy-l H-indole-3-carboxamide CQ98

[0535] Amount made: 4.3 mg. LCMS m/z IQl [M+H] ^4" , purity (UV/MS) 100/90.

N-(3,4-dichlorobenzyl)-7-ethyl-l-r3-('4-phenethylpiperazin-l -yl ^" )propyl>-lH-indole-3- carboxamide C099

[0536J Amount made: 9.5 mg. LCMS m/z SIl [M+H] ⁺ , purity (UV/MS) 100/90.

N-( ^' 3 _< 4-dichlorobenzyl ^' )-7-isopropoxy-l-f3-(4-( ^' 3-phenoxypropyl)piperazin-l-yl)propyl')-lH- indole-3-carboxamide ClOO

[0537] Amount made: 4.0 mg. LCMS m/z 637 [M+H] ⁺ , purity (UV/MS) 84/40.

N-fSλ-dichlorobenzvn-l-π^dihvdro-lH-pyridorL∑-aipyraz in-lCόHJH.SH.gH.gaH)- yl)propyl>7-methoxy- 1 H-indole-3-carboxamide ClOl

[0538] Amount made: 1.8 mg. LCMS m/z 529 [M+H] ⁺ , purity (UV/MS) 100/100.

l-r3-ri-benzylpyrrolidin-3-ylamino)propyl)-N-(3-fluoroben zyl)-7-methoxy-lH-indole-3- carboxamide Cl 02

[0539] Amount made: 2.1 mg. LCMS m/z 515 [M+H] ⁺ , purity (UV/MS) 98/80.

N-Oλ-dichlorobenzvn-l-O-fdihvdro-lH-pyridoπ^-alpyrazin- ∑rόHJH^H^H.PaHV yl)propyl)-7-ethyl-l H-indole-3-carboxamide C103

[0540] Amount made: 3.3 mg. LCMS m/z 527 [M+H] ⁺ , purity (UV/MS) 99/100.

1 -(3-(4-(2-r4-chlorophenoxy)ethyl)piperazin- 1 -yl)propyl ^' )-N-(3-fluorobenzyπ-7-methoxy- 1 H- indole-3-carboxamide C104

[0541] Amount made: 8.1 mg. LCMS m/z 579 [M+H] ⁺ , purity (UV/MS) 100/100.

7-methoxy-N-( ^' 3-methylbenzyl ^' )-l-(3-(4-phenethylpiperazin-l-yπpropyl)-lH-indole-3- carboxamide C105

[0542] Amount made: 7.4 mg. LCMS m/z 525 [M+H] ⁺ , purity (UV/MS) 100/90.

7-methoxy-N-(3-methylbenzy IV 1 -(3-f4-f 3-phenoxypropy0piperazin- 1 -yPpropyl)- 1 H-indole- 3-carboxamide C106

[0543] Amount made: 6.6 mg. LCMS m/z 555 [M+H] ⁺ , purity (UV/MS) 81/60.

1 -(3-(4-(2-chloro-6-f1uorobenzy I)- 1 ,4-diazepan- 1 -yl)propylV7-methoxy-N-(3-methylbenzy I)- 1 H-indole-3-carboxamide C107

[0544] Amount made: 4.7 mg. LCMS m/z 577 [M+H] ⁺ , purity (UV/MS) 100/80.

7-methoxy-N-( ^" 3-methylbenzyl)-l-(3-(4-(2-morpholino-2-oxoethyl)piperazin-l -yl)propyl)- 1 H-indole-3-carboxamide C108

[0545] Amount made: 5.6 mg. LCMS m/z 548 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3-(4-(2-(diisopropyJamino')ethvI ^' )piperazin- 1 -yl)propylV7-methoxy-N-f 3-methylbenzyl> lH-indole-3-carboxamide C109

[0546] Amount made: 7.2 mg. LCMS m/z 548 [M+H] ⁺ , purity (UV/MS) 99/80.

1-( ^" 3-Cl -benzy lpyrrolidin-3 -y lamino ^' )propyl>-7-methoxy-N-f 3 -methylbenzylV 1 H-indole-3- carboxamide CIlO

[0547] Amount made: 3.8 mg. LCMS m/z 51 1 [M+H] ⁺ , purity (UV/MS) 99/70.

N-π^-dichlorobenzvn-l-rS-rdihydro-lH-pyridoπ ^-aipyrazin-σCόHJH.SH^H.gaHV yl)propyl>-7-isopropoxy-lH-indole-3-carboxamide ClIl

[0548] Amount made: 4.0 mg. LCMS m/z 557 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -(3-((I R,3r,5S)-3-(2-(3-chloro-4-fluorophenyn-2-oxoethylV8-azabicvc lof3.2.1 loctan-8- y0propylV7-metrioxy-N-(3-methvIbenzviyiH-indoIe-3-carboxarni de C112

[0549] Amount made: 7.6 mg. LCMS m/z 616 [M+H] ⁺ , purity (UV/MS) 95/70.

N-(3,4-dichlorobenzyl)-7-methoxy-l -(3-(4-(3-phenoxypropyl)piperazin-l -yDpropylVl H- indole-3-carboxamide Cl 13

[0550] Amount made: 6.9 mg. LCMS m/z 609 [M+H] ⁺ , purity (UV/MS) 98/40.

N-(3-fluorobenzylVl -(3-r(lS,4SV5-(2-(4-fluorophenoxy)ethyl)-2.5-diazabicvclor2. 2.21octan- 2-v0propyl)-7-methoxy- 1 H-indole-3 -carboxamide Cl 14

[0551] Amount made: 6.8 mg. LCMS m/z 589 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3-fluorobenzyl)-l-f3-f(lR.5S)-3-(2-(4-fluorophenoxy)ethyl V3.8-diazabicvclo| ^" 3.2.11octan- 8-yl)propyl)-7-methoxy-l H-indole-3 -carboxamide Cl 15

[0552] Amount made: 3.9 mg. LCMS m/z 589 [M+H] ⁺ , purity (UV/MS) 99/70.

N-(3,4-dichloroben2yl)-l-(3-((lS,4S)-5-(2-(4-fluorophenoxy ^> )ethylV2.5- diazabicyclo[ ^' 2.2.2]octan-2-vDpropyl)-7-methoxy-l H-indole-3 -carboxamide Cl 16

[0553] Amount made: 1.7 mg. LCMS m/z 639 [M+H] ⁺ , purity (UV/MS) 100/90.

N-f3,4-dichlorobenzylVl-f3-fflR.5SV3-f2-f4-fluorophenoxy ^' )ethylV3.8- diazabicvclor3.2.11octan-8-yl)propyiy7-methoxy-lH-indole-3-c arboxarnide Cl 17

[0554] Amount made: 5.2 mg. LCMS m/z 639 [M+H] ⁺ , purity (UV/MS) 93/80.

N-(3,4-dichlorobenzyl)-7-methoxy-l -(3-(4-(3-phenoxypropyiy 1 ,4-diazepan- 1 -vOpropylV 1 H- indole-3-carboxamide C118

[0555] Amount made: 9.6 mg. LCMS m/z 623 [M+H] ⁺ , purity (UV/MS) 100/90.

l-π-CnRJr.SSVS-r∑-^-chlorophenylVσ-oxoethylVδ-azabic vclop.σ. noctan-S-vnpropylVN- O-Zt-dichlorobenzyiyT-rnethoxy-l H-indole-3-carboxamide C119

[0556] Amount made: 1.7 mg. LCMS m/z 652 [M+H] ⁺ , purity (UV/MS) 91/60.

N-π.4-dichlorobenzvI')-7-methoχy-l-r3-CπR.3r.5SV3-r2-o xo-2-(pyridin-2-yl')ethylV8- azabicycloF3.2. l]octan-8-yl)propyiyi H-indole-3-carboxamide C120

[0557] Amount made: 4.0 mg. LCMS m/z 619 [M+H] ⁺ , purity (UV/MS) 99/90.

l-(3-(Tl S.4S)-5-(2-r4-fluorophenoxy ^' )ethyl')-2,5-diazabicyclor2.2.21octan-2-vnpropylV7- methoxy-N-Q-methylbenzyiyiH-indole-S-carboxamide C121

[0558] Amount made: 2.8 mg. LCMS m/z 585 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3,4-dichlorobenzyl ^' )-l-D-(4-(2-(4-fluorophenoxy ^' )ethyl ^" )-l,4-dia2epan-l-yπpropyl>-7- methoxy-1 H-indole-3-carboxarnide C122

[0559] Amount made: 3.4 mg. LCMS m/z 627 [M+H] ⁺ , purity (UV/MS) 99/90.

l-(3-(dR.5S ^' )-3-r2-f4-fluorophenoxy ^' )ethyl)-3.8-diazabicvclor3.2.noctan-8-yπpropyl>-7- methoxy-N-(2-methylbenzyl> 1 H-indole-3-carboxamide C123

[0560] Amount made: 5.1 mg. LCMS m/z 585 [M+H] ⁺ , purity (UV/MS) 100/70.

N-( 3-fluorobenzy X)- 1 -C3 -(4-f2-(4-fluorophenoxy)ethyl ^' )- 1 ,4-diazepan- 1 -yl)propyl)-7-methoxy- 1 H-indole-3-carboxamide C 124

[0561] Amount made: 1.8 mg. LCMS m/z 577 [M+H] ⁺ , purity (UV/MS) 100/90.

N-f 3 -fluorobenzvO-7-methoxy- 1 -(3-(4-f2-phenoxyethyl)piperidin- 1 -vDpropylV 1 H-indoIe-3- carboxamide C125

[0562 J Amount made: 2.9 mg. LCMS m/z 544 [M+H] ⁺ , purity (UV/MS) 100/70.

N-G-fluorobenzvn-T-methoxy-l-O-rdRJr^SVS-q-oxo^-rpyridin^ -vnethylVδ- azabicvclof3.2.11octan-8-yl)propylVlH-indole-3-carboxarnide Cl 26

[0563] Amount made: 1.2 mg. LCMS m/z 569 [M+H] ⁺ , purity (UV/MS) 92/70.

1 -G-CfI R.3r.5SV3-(2-r4-chlorophenvn-2-oxoethylV8-azabicvclor3.2.1 loctan-8-yl)propylVN- (3-fluorobenzylV7-methoxy-lH-indole-3-carboxamide C127

[0564] Amount made: 5.3 mg. LCMS m/z 602 [M+H] ⁺ , purity (UV/MS) 100/70.

l-( ^' 3-rriR.3r.5SV3-(2-r3,4-dichlorophenyn-2-oxoethvn-8-azabicvcl or3.2.11octan-8- yl)propyl)-N-(3-fluorobenzyπ-7-methoxy-lH-indole-3-carboxam ide C128

[0565] Amount made: 5.6 mg. LCMS m/z 636 [M+H] ⁺ , purity (UV/MS) 100/90.

l-0-(4-f2-f4-fluorophenoxy)ethviyiλ-diazepan-l-yl)propyl V7-methoxy-N-f2- methylbenzyl)-lH-indole-3-carboxamide C129

[0566] Amount made: 3.1 mg. LCMS m/z 573 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3-fluorobenzvD-7-methoxy- 1 -(3-C4-C 3-phenoxypropyl> 1.4-diazepan- 1 -y Ppropy I)- 1 H- indole-3-carboxamide C130

[0567] Amount made: 2.4 mg. LCMS m/z 573 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3,4-dichlorobenzyπ-7-methoxy-l-(3-('4-(2-phenoxyethyl)pi peridin-l-yl)propyl ^' )-lH- indoIe-3-carboxamide C131

[0568] Amount made: 3.2 mg. LCMS m/z 594 [M+H] ⁺ , purity (UV/MS) 90/70.

N-f3,4-dichlorobenzylV7-ethyl-l-r3-rflR.3r,5S)-3-r2-oxo-2 -rpyridin-2-yl)ethylV8- azabicvclo[3.2.1]octan-8-yl)propylMH-indole-3-carboxamide C132

[0569] Amount made: 1.8 mg. LCMS m/z 617 [M+H] ⁺ , purity (UV/MS) 99/80.

7-methoxy-N-r2-methylbenzyl ^' )-l-(3-f4-r2-phenoxyethyl ^' )piperidin-l-yl')propyl>lH-indole-3- carboxamide C133

[0570] Amount made: 4.5 mg. LCMS m/z 540 [M+H] ⁺ , purity (UV/MS) 99/60.

1 -C3-f 1 -benzylpyrrolidin-3-ylamino)propylV7-methoxy-N-f2-methylbenz yl)-l H-indole-3- carboxamide C134

[0571] Amount made: 2.9 mg. LCMS m/z 51 1 [M+H] ⁺ , purity (UV/MS) 99/80.

1 -f3-(Yl RJr.SSVS-Q-fS-chloro^-fluorophenylVσ-oxoethvn-S-azabicvclof 3.2.1 ^" |octan-8- vπpropylV7-methoxy-N-r2-methylbenzyl)-lH-indole-3-carboxami de C135

[0572] Amount made: 1.5 mg. LCMS m/z 616 [M+H] ⁺ , purity (UV/MS) 83/50.

7-methoxy-N-r2-methylbenzyl ^* )-l-( ^' 3-r4-(2-phenoxyethyl ^' )-K4-diazepan-l-yl)propyl)-lH- indole-3-carboxamide C136

[0573] Amount made: 2.2 mg. LCMS m/z 555 [M+H] ⁺ , purity (UV/MS) 98/80.

7-methoxy-N-r2-methylbenzylVl-( ^' 3-fπR.3r,5SV3-f2-oxo-2-(pyridin-2-yl)ethyl>8- azabicyclo[3.2.1 ]octan-8-y0propyiy lH-indole-3-carboxamide C137

[0574] Amount made: 3.8 mg. LCMS m/z 565 [M+H] ⁺ , purity (UV/MS) 96/80.

1 -(3-(dihvdro-l H-Dyridoπ .σ-alpyrazin-σCάH JH,8H.9H.9aHVyl)propylVN-(3-fluorobenzvn- 7-methoxy-lH-indole-3-carboxamide C138

[0575] Amount made: 3.0 mg. LCMS m/z 479 [M+H] ⁺ , purity (UV/MS) 99/80.

l-(3-(πR.3r,5SV3-(2-r4-chlorophenvn-2-oxoethvn-8-azabicv clor3.2.1]octan-8-ynpropyl>-7- methoxy-N-(2-methylbenzyl)-lH-indole-3-carboxamide C139

[0576] Amount made: 1.2 mg. LCMS m/z 598 [M+H] ⁺ , purity (UV/MS) 98/80.

l -(3-(πR.3r,5S)-3-C2-f3,4-dichlorophenyn-2-oxoethyl)-8-azabi cvclor3.2.11octan-8- y0ρropyl>7-methoxy-N-(2-methylbenzyl>lH-indole-3 -carboxamide Cl 40

[0577] Amount made: 2.7 mg. LCMS m/z 632 [M+H] ⁺ , purity (UV/MS) 100/80.

7-methoxy-N-(2-methylbenzyl> 1 -(3-(4-(3-phenoxypropyD- 1.4-diazepan- 1 -vDpropylV 1 H- indole-3-carboxamide C141

[0578] Amount made: 5.0 mg. LCMS m/z 569 [M+H]\ purity (UV/MS) 100/90.

l-r3-( ^" 2,3-dihydro-lH-inden-2-ylamino)propylV7-methoxy-N-(3-methylb en _-- yl)-lH-indole-3- carboxamide C142

[0579] Amount made: 4.6 mg. LCMS m/z 468 [M+H]\ purity (UV/MS) 89/70.

1 -( ^" 3-(2,3-dihydro- 1 H-inden-2-y lamino)propyl VN-isobutyl-7-methoxy- 1 H-indole-3- carboxamide C143

[0580] Amount made: 5.2 mg. LCMS m/z 420 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -f S-π-re-^-chlorophenylVσ-bxoethviyS-azabicvclo^ .2.11octan-8-yl)propyiy7-methoxy-N- (3-methylbenzyiyi H-indole-3-carboxamide C144

[0581] Amount made: 7.6 mg. LCMS m/z 598 [M-Hl] ⁺ , purity (UV/MS) 98/70.

1 -(3-(3-(2-(4-chlorophenyl ^' )-2-oxoethviy8-azabicvclor3.2. l]octan-8-vOpropyiyN-isobutyl-7- methoxy-1 H-indole-3-carboxamide C145

[0582] Amount made: 6.4 mg. LCMS m/z 550 [M+H] ⁺ , purity (UV/MS) 98/70.

l-(3-(3-(2-chlorobenzyl)piperidin-l-yl)propyl)-7-methoxy- N-r3-methylbenzyl)-lH-indole-3- carboxamide C146

[0583] Amount made: 4.3 mg. LCMS m/z 544 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -(3-f3-(2-chlorophenoxy)-8-azabicyclof3.2.1 ^" |octan-8-vOpropyl)-7-methoxy-N-(3- methylbenzyl)-l H-indole-3-carboxamide C147

[0584] Amount made: 5.4 mg. LCMS m/z 572 purity (UV/MS) 100/80.

1 -D-O-Q-chlorophenoxyVS-azabicyclofS^, 1 ]octan-8-yQpropyl>N-isobutyl-7-methoxy- 1 H- indole-3 -carboxamide Cl 48

[0585] Amount made: 4.6 mg. LCMS m/z 524 [M+H] ⁺ , purity (UV/MS) 98/80.

l-r3-( ^" 3-r4-chlorophenethylV8-azabicyclof3.2.11octan-8-yl)propyl> ;-7-niethoxy-N-(3- methylbenzyl>-lH-indole-3-carboxamide C149

[0586] Amount made: 6.9 mg. LCMS m/z 584 [M+H] ⁺ , purity (UWMS) 94/60.

l-π-rS-^-chlorophenethylVS-azabicvclorS^.lloctan-S-vπpr opylVN-isobutyl-y-methoxy- lH-indole-3-carboxamide C150

[0587] Amount made: 5.8 mg. LCMS m/z 536 [M+H] ⁺ , purity (UWMS) 97/70.

1 -π-r3-r4-chlorophenoxy)-8-azabicvclo[3.2.1 loctan-S-yppropy^-methoxy-N-f 3- methylbenzylVlH-indole-3-carboxamide Cl 51

[0588] Amount made: 4.4 mg. LCMS m/z 572 [M+H] ⁺ , purity (UV/MS) 87/70.

l-(3-f3-r4-chlorophenoxy)-8-azabicyclor3.2.noctan-8-yl')prop yl ^' )-N-isobutyl-7-methoxy-lH- indole-3-carboxarnide C152

[0589] Amount made: 3.0 mg. LCMS m/z 524 [M+H] ⁺ , purity (UV/MS) 94/70.

1 -(3-C3 -r4-chlorophenoxy)piperidin- 1 -vDpropylV7-methoxy-N-(3-methylbenzy IV 1 H-indole- 3-carboxamide Cl 53

[0590] Amount made: 4.3 mg. LCMS m/z 546 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-(3-r4-chlorophenoxy ^' )piperidin-l-yl ^' )propyl ^' )-N-isobutyl-7-methoxy-lH-indole-3- carboxamide C154

[0591] Amount made: 5.8 mg. LCMS m/z 498 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3-f3-f4-fluorophenoxyV8-azabicvcIof3.2.1 ^" |octan-8-y0propylV7-methoxy-N-(3- methylbenzy IV 1 H-i ndole-3 -carboxamide Cl 55

[0592] Amount made: 5.6 mg. LCMS m/z 556 [M+H] ⁺ , purity (UV/MS) 92/60.

l-( ^' 3-(3-r4-fluorophenoxyV8-azabicyclo[3.2.11octan-8-yPpropylVN- isobutyI-7-methoxy-l H- indole-3-carboxamide C156

[0593] Amount made: 4.2 mg. LCMS m/z 508 [M+H] ⁺ , purity (UV/MS) 98/80.

l-(3-(4-r2-( ^' 4-chloronaphthalen-l-yloxy)ethyl)piperazin-l-yl)propyl)-7-me thoxy-N-(2- methylbenzylVlH-indole-3-carboxamide C157

[0594] Amount made: 2.1 mg. LCMS m/z 625 [M+H] ⁺ , purity (UV/MS) 100/100.

l-f3-(4-f2-(4-chloronaphthalen-l-yloxy)ethvπpiperazin-l- yI)propyl)-7-methoxy-N-(3- methylbenzylVlH-indole-3-carboxamide C158

[0595] Amount made: 0.9 mg. LCMS m/z 625 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3-(4-(2-(4-chloronaphthalen- 1 -yloxytethvOpiperazin- 1 -yDpropyl)-N-isobutyl-7-methoxy- lH-indole-3-carboxamide C159

[0596] Amount made: 0.8 mg. LCMS m/z 517 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3-(4-r2-(4-chlorophenoxy)ethyl ^' )piperazin- 1 -yl)propyl)-7-methoxy-N-(3-methylbenzylV l H-indole-3-carboxamide C16Q

[0597] Amount made: 6.6 mg. LCMS m/z 575 [M+H] ⁺ , purity (UV/MS) 100/90.

l -(3-(4-(2-(4-chlorophenoxy)ethvπpiperazin-l-vπpropyl>-N -(3,4-dichlorobenzyπ-7-ethyl- lH-indole-3-carboxamide C161

[0598] Amount made: 8.8 mg. LCMS m/z 621 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -(3-(4-(2-(4-chlorophenoxy)ethyl)piperazin-l -yl)propylV-N-isobutyl-7-methoxy-l H-indole- 3-carboxamide C 162

[0599] Amount made: 7.8 mg. LCMS m/z 527 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-(4-(2-(4-chlorophenoxy)ethyl ^' )piperidin-l-vπpropylV7-methoxy-N-(3-methylbenzyl> lH-indole-3-carboxamide C163

[0600] Amount made: 3.1 mg. LCMS m/z 574 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3"(4-(2-(4-chlorophenoxy ^' )ethyl ^' )piperidin-l -vPpropyl>N-isobutyl-7-methoxy-l H-indole- 3-carboxamide C164

[0601] Amount made: 0.6 mg. LCMS m/z 526 [M+H]\ purity (UV/MS) 100/90.

1 -(3-(4-f2,4-dichlorobenzyl)piperazin-l -yl)propyl>7-methoxy-N-(3-methyIbenzyiy 1 H- indole-3-carboxamide C165

[0602] Amount made: 2.4 mg. LCMS m/z 579 [MH-H] ⁺ , purity (UV/MS) 100/90.

l-(3-(4-(2,4-dichlorobenzyπpiperazin-l-vπpropylVN-isobu tyl-7-methoxy-lH-indole-3- carboxamide C 166

(0603] Amount made: 7.3 mg. LCMS m/z 531 [MH-H] ⁺ , purity (UV/MS) 100/100.

1 -(3-f4-(2-chlorobenzyl> 1 λ-diazepan-1 -yl)propyl>7-methoxy-N-(3-methylbenzyl)- 1 H- indole-3-carboxamide C167

[0604] Amount made: 4.3 mg. LCMS m/z 559 [M+H] ⁺ , purity (UV/MS) 97/80.

l-(3-(4-(2-chlorobenzvπ-l,4-diazepan-l-yl)propyl')-N-iso butyl-7-methoxy-lH-indole-3- carboxamide C168

[0605] Amount made: 4.1 mg. LCMS m/z 51 1 [MH-H] ⁺ , purity (UV/MS) 98/80.

l-(3-(4-(2-chlorophenoxy)piperidinrl-yl ^' )propyl ^' )-7-methoxy-N-(3-methylbenzyl ^* )-lH-indole- 3-carboxamide C169

[0606] Amount made: 9.8 mg. LCMS m/z 546 [MH-H] ⁺ , purity (UV/MS) 89/50.

l -(3-(4-(2-chlorophenoxy)piperidin-l-yl)propyl ^' )-N-isobu-yl-7-methoxy-lH-indole-3- carboxamide C170

[0607] Amount made: 8.5 mg. LCMS m/z 498 [MH-H] ⁺ , purity (UV/MS) 94/70.

l-(3-(4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperaz in-l-yl)propylV7-methoxy-N-(3- methylbenzyiyiH-indole-3-carboxarnide C171

[0608] Amount made: 9.4 mg. LCMS m/z 600 [MH-H] ⁺ , purity (UV/MS) 100/100.

l-r3-(4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperaz in-l-yl)propyl)-N-(3-chlorobenzyπ- 7-methoxy-lH-indole-3 -carboxamide C172

[0609] Amount made: 2.4 mg. LCMS m/z 620 [M+H] ⁺ , purity (UV/MS) 100/100.

W 2

1 -(3-(4-( S-chloro-S-ftrifluoromethvDpyridin^-vDpiperazin- 1 -yl)propyl>N-isobutγi-7- methoxy- 1 H-indole-3-carboxamide C173

[0610] Amount made: 8.2 mg. LCMS m/z 552 [M+H] ⁺ , purity (UV/MS) 100/100.

l-O-^-O-chlorophenoxy^piperidin-l-vDpropyiyy-methoxy-N-O- methylbenzylVlH-indole- 3-carboxamide C174

[0611] Amount made: 4.9 mg. LCMS m/z 546 [M+H] ⁺ , purity (UV/MS) 100/80.

l-( ^" 3-(4-r3-chlorophenoxy)piperidin-l-yl)propyl>-N-isobutyl-7 -methoxy-lH-indole-3- carboxamide C 175

[0612] Amount made: 5.8 mg. LCMS m/z 498 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3-f4-(4-chlorophenoxy)piperidin-l -yl)propyI>7-methoxy-N-(3-methylbenzyl)-l H-indole- 3-carboxamide C176

[0613J Amount made: 6.6 mg. LCMS m/z 546 [M+H] ⁺ , purity (UV/MS) 78/50.

[0614] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.71 - 7.55 (m, 2H), 7.34 - 7.09 (m, 7H) ₅ 6.81 - 6.78 (m, 2H), 6.72 - 6.69 (m, IH), 4.63 - 4.55 (m, 2H), 4.47 - 4.40 (m, 2H), 3.97 (s, 3H), 3.63 - 2.89 (m, 9H), 2.37 (s, 3H), 2,35 -2.09 (m, 4H).

l-CS^-^-chlorophenoxy^piperidin-l-vDpropylVN-isobutyl^-me thoxy-lH-indole-S- carboxamide C 177

[0615] Amount made: 3.5 mg. LCMS m/z 498 [M+H] ⁺ , purity (UV/MS) 88/60.

1 -(3-(4-(4-fluorobenzyI)- 1,4-diazepan-l -yl)propylV7-methoxy-N-(3-methylbenzyl ^' )- IH- indole-3-carboxamide C178

[0616] Amount made: 6.5 mg. LCMS m/z 543 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-(4-C4-fluorobenzyl')-1.4-dia2epan-l-yπpropyl ^* )-N-isobutyl-7-methoxy-lH-indole-3- carboxamide C179

[0617] Amount made: 5.6 mg. LCMS m/z 495 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-C4-( ^' 4-fluorophenoxy)piperidin-l-yl)propyl>-7-methoxy-N-π-met hylbenzyl ^' )-lH-indole- 3-carboxamide C180

[0618] Amount made: 2.5 mg. LCMS m/z 530 [M+H] ⁺ , purity (UV/MS) 94/70.

l-(3-r4-(4-fluorophenoxy ^' )piperidin-l-yl)propyl ^' )-N-isobutyl-7-methoxy-lH-indole-3- carboxamide C181

[0619] Amount made: 2.3 mg. LCMS m/z 482 [M+H] ⁺ , purity (UV/MS) 96/80.

l-(3-( ^' 4-rbenzofd]thia2ol-2-yl)piperidin-l-yl)propyl>-7-methoxy- N-r3-methylbenzyl>-lH- indole-3-carboxamide C182

[0620] Amount made: 6.3 mg. LCMS m/z 553 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -(3-(4-(benzo[d]thiazol-2-yl')piperidin- 1 -yl)propyl ^' )-N-(3-chIorobenzylV7-methoxy- 1 H- indole-3-carboxamide C183

[0621] Amount made: 3.3 mg. LCMS m/z 573 [M+H] ⁺ , purity (UV/MS) 98/70.

l-(3-r4-(benzo[d1thiazol-2-yl)piperidin-l-vπpropyl)-N-is obutyl-7-methoxy-lH-indole-3- carboxamide C184

[0622] Amount made: 6.9 mg. LCMS m/z 505 [M+H] ⁺ , purity (UV/MS) 97/70.

l-(3-(4-benzoylpiperidin-l-yl)propyl ^' )-7-methoxy-N-( ^' 3-methylbenzyl)-l H-indole-3- carboxamide Cl 85

[0623] Amount made: 3.8 mg. LCMS m/z 524 [M+H] ⁺ , purity (UV/MS) 95/60.

, l-(3-(4-benzoylpiperidin-l-yπpropylVN-(3-chlorobenzvπ-7-me thoxy-lH-indole-3- carboxamide Cl 86

[0624] Amount made: 1.1 mg. LCMS m/z 544 [M+H] ⁺ , purity (UV/MS) 98/70.

l-(3-r4-benzoylpiperidin-l-yl)propyl)-N-isobutyl-7-methox y-lH-indole-3-carboxamide C187

[0625] Amount made: 5.4 mg. LCMS m/z 476 [M+H] ⁺ , purity (UV/MS) 100/80.

W

l-r3-r4-butylpiperidin-l-yl)propyl ^' )-7-methoxy-N-( ^' 3-methylbenzyl)-lH-indole-3- carboxamide C188

[0626] Amount made: 5.3 mg. LCMS m/z 476 [M+H] ⁺ , purity (UV/MS) 99/90.

1 -f 3-(4-butylpiperidin- 1 -yDpropyiyN-O-chlorobenzyl ^' W-rnethoxy- 1 H-indole-3-carboxamide C189

[0627] Amount made: 5.8 mg. LCMS m/z 496 [M+H] ⁺ , purity (UV/MS) 99/90.

1 -( ^" 3-( ^" 4-butylpiperidin- 1 -yl)propyl>N-isobutyI-7-methoxy- 1 H-indole-3-carboxamide C190 [0628] Amount made: 2.8 mg. LCMS m/z 428 [M+H] ⁺ , purity (UV/MS) 100/90.

7-methoxy- 1 -(S-^-Q-methoxyphenyPpiperidin- 1 -yPpropy D-N-O-methylbenzylV 1 H-indole- 3-carboxamide Cl 91

[0629] Amount made: 9.7 mg. LCMS m/z 526 [M+H] ⁺ , purity (UV/MS) 96/70.

7-methoxy-N-(3-methylbenzyl)-l-r3-(2-phenoxyethylamino ^' )propyl)-lH-indole-3- carboxamide Cl 92

[0630] Amount made: 4.8 mg. LCMS m/z All [M+H] ⁺ , purity (UV/MS) 91/70.

7-methoxy-N-r3-methylbenzylVl-r3-C3-('2-oxo-2-phenylethyl V8-azabicyclo[3.2.11octan-8- yl)propyD-l H-indole-3-carboxamide C193

[0631] Amount made: 4.2 mg. LCMS m/z 564 [M+H] ⁺ , purity (UV/MS) 96/80.

7-methoxy-N-(3-methylbenzyl)-l -r3-(3-pentyl-8-azabicvclo [3.2.1 ]octan-8-yπpropyl ^' )- I H- indole-3 -carboxamide C 194

[0632] Amount made: 2.8 mg. LCMS m/z 516 [M+H] ⁺ , purity (UV/MS) 97/90.

7-methoxy-N-(3-methylbenzyl V 1 -D-π-phenethvI-δ-azabicycloD .2.1 loctan-8-yl)ρropyl)- 1 H- indole-3 -carboxamide C195

[0633] Amount made: 5.0 mg. LCMS m/z 550 [M+Hf, purity (UV/MS) 91/70.

7-methoxy-N-(3-methylbenzyl)-l-( ^' 3-r4-( ^' 2-oxoindolin-l-yπpiperidin-l-yl>propyl)-lH-indole- 3-carboxamide C 196

[0634] Amount made: 0.9 mg. LCMS m/z 551 [M+H] ⁺ , purity (UV/MS) 94/80.

7-methoxy-N-( ^' 3-methylbenzyl)- 1 -f3-(4-(2-phenoxyethyl)piperazin- 1 -vDpropyl)- 1 H-indole-3- carboxamide C197

[0635] Amount made: 8.1 mg. LCMS m/z 541 [M+H] ⁺ , purity (UV/MS) 100/100.

vDpropyl)- 1 H-indole-3-carboxamide C198

[0636] Amount made: 6.9 mg. LCMS m/z 565 [M+H] ⁺ , purity (UV/MS) 98/70.

7-methoxy-N-( ^' 3-methylbenzyl)-l-r3-( ^' 4-(3-(pyridin-4-ylVl,2.4-oxadiazol-5-vπpiperidin-l - vDpropyl)- 1 H-indole-3-carboxamide C199

[0637] Amount made: 8.0 mg. LCMS m/z 565 [M+H] ⁺ , purity (UV/MS) 98/60.

7-methoxy-N-(3-methylbenzyl>-l-(3-(4-oxospirorchroman- 2.4'-piperidine]-r-yl)propyl)-lH- indole-3-carboxamide C200

[0638] Amount made: 6.2 mg. LCMS m/z 552 [M+H] ⁺ , purity (UV/MS) 99/90.

7-methoxy-N-( ^" 3-methylbenzyl ^* )-l-f3-(4-phenethyl-l ,4-diazepan-l-yl)propyl)-l H-indole-3- carboxamide C201

[0639] Amount made: 6.3 mg. LCMS m/z 539 [M+H] ⁺ , purity (UV/MS) 100/90.

N-r3.4-dichlorobenzyl)-7-isopropoxy-l-(3-(dR,3r,5S)-3-(2-oxo -2-(pyridin-2-vnethylV8- azabicyclor3.2.1 ^" ]octan-8-yπpropyl)-l H-indole-3-carboxamide C202

[0640] Amount made: 4.3 mg. LCMS m/z 647 [M+H] ⁺ , purity (UV/MS) 98/80.

N-f3-chlorobenzy I)- 1 -(3-(2,3-dihydro- 1 H-inden-2-y lamino)propyl)-7-methoxy- 1 H-indole-3- carboxamide C203

[0641] Amount made: 5.7 mg. LCMS m/z 488 [M+H] ⁺ , purity (UV/MS) 94/90.

N-π-chlorobenzylVl-O-rS-Q-^-chlorophenylVσ-oxoethylVδ- azabicvclorS^. lloctan-S- y0propylV7-rnethoxy-l H-indole-3-carboxamide C2Q4

[0642] Amount made: 7.7 mg. LCMS m/z 618 [M+H] ⁺ , purity (UV/MS) 98/60.

N-(3 -chlorobenzyl)- 1 -f 3-(3-(2-chlorobenzyl)piperidin- 1 -yl)propyl)-7-:methoxy- 1 H-indole-3 - carboxamide C205

[0643] Amount made: 4.2 mg. LCMS m/z 564 [M+H] ⁺ , purity (UV/MS) 98/80.

N-(3-chlorobenzylVl-D-(3-(2-chlorophenoxy)-8-azabicvclor3.2. 11octan-8-yl')propyl ^' )-7- methoxy-1 H-indole-3-carboxamide C206

[0644] Amount made: 4.5 mg. LCMS m/z 592 [M+H] ⁺ , purity (UV/MS) 100/80.

N-(3-chlorobenzyl)-l -r3-(3-(4-chlorophenethyl)-8-azabicyclo[3.2.1 ]octan-8-vI)propylV7- methoxy-1 H-indole-3-carboxamide C207

[0645] Amount made: 6.4 mg. LCMS m/z 604 [M+H] ⁺ , purity (UV/MS) 97/60.

N-( ^* 3-chlorobenzyl ^' )-l-(3-(3-('4-chlorophenoxy)-8-azabicyclo[3.2.1]octan-8-yl)p ropyl)-7- methoxy- 1 H-indole-3-carboxamide C208

[0646] Amount made: 3.4 mg. LCMS m/z 592 [M+H] ⁺ ₅ purity (UV/MS) 87/70.

N-(3-chlorobenzyl)- 1 -( ^" 3-(3-(4-chlorophenoxy)piperidin- 1 -yDpropy l>7-methoxy- 1 H-indole- 3-carboxamide C209

[0647] Amount made: 7.2 mg. LCMS m/z 566 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3-chlorobenzyl)-l-( ^' 3-(3-(4-fluorophenoxy)-8-azabicvcIo[3.2.11octan-8-yl)propyl) -7- methoxy- 1 H-indole-3-carboxamide C210

[0648] Amount made: 4.5 mg. LCMS m/z 576 [M+H] ⁺ , purity (UV/MS) 97/70.

N-(3-chlorobenzyl)-l-(3-(4-(2-(4-chloronaphthalen-l-yloxy )ethyl)piperazin-l-vDpropyl)-7- methoxy-1 H-indole-3-carboxamide C211

[0649] Amount made: 1.9 mg. LCMS m/z 645 [M+H] ⁺ , purity (UV/MS) 100/100.

N-(3-chIorobenzyl')-l-(3-('4-( ^' 2-r4-chlorophenoxy')ethvπpiperazin-l-yl ^' )propyl>-7-methoxy- lH-indole-3-carboxamide C212

[0650] Amount made: 6.7 mg. LCMS m/z 595 [IVH-H] ⁺ , purity (UV/MS) 1 GO/100.

N-(3-chlorobenzy I)- 1 -(3-(4-(2-(4-chlorophenoxy)ethy Dpiperidin- 1 -y Ppropyl)-7-methoxy- 1 H- indole-3-carboxamide C213

[0651] Amount made: 4.2 mg. LCMS m/z 594 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3-chlorobenzyl ^' )-l-r3-r4-( ^' 2-chloroben2λ ^f π-K4-diazepan-l-yl')propylV7-methoxy-lH- indole-3-carboxamide C214

10652] Amount made: 4.0 mg. LCMS m/z 579 [M+H] ⁺ , purity (UV/MS) 100/90.

N-(3-chlorobenzyl)-l-(3-('4-r2-chlorophenoxy)piperidin-l-yπ propyl ^' )-7-methoxy-lH-indole- 3-carboxamide C215

[0653] Amount made: 5.5 mg. LCMS m/z 566 [M+H] ⁺ , purity (UV/MS) 93/70.

N-(3-chlorobenzyl)-l-(3-(4-(3-chloroρhenoxy ^' )piperidin-l-yl)propyl ^' )-7-methoxy-lH-indole- 3-carboxamide C216

[0654] Amount made: 5.5 mg. LCMS m/z 566 [M+H] ⁺ , purity (UV/MS) 98/90.

N-(3-chlorobenzyl)-l-(3-(4-(4-chlorophenoxy)piperidin-l-y πpropyl)-7-methoxy-lH-indole- 3-carboxamide C217

[0655] Amount made: 4.2 mg. LCMS m/z 566 [M+H] ⁺ , purity (UV/MS) 79/60.

[0656] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 7.71 -7.61 (m, 2H), 7.39 - 7.13 (m, 7H), 6.80 - 6.67 (m, 3H), 4.73 - 4.48 (m, 4H), 3.98 (s, 3H) ₅ 3.57 - 3.39 (m, 2H), 3.01 - 2.93 (m, 3H) ₃ 2.72 - 2.04 (m, 8H).

N-(3-chlorobenzyl)-l -(3-(4-(4-fluorobenzyl)- 1 ,4-diazepan-l -yl)propyl>7-methoxy-l H- indole-3-carboxamide C218

[0657] Amount made: 5.9 mg. LCMS m/z 563 [M+H] ⁺ , purity (UV/MS) 100/90.

N-O-chlorobenzyP- 1 -("3 -f 4-f 4-fluorophenoxy)piperidin- 1 -yπpropyl)-7-methoxy- 1 H-indole-3 - carboxamide C219

[0658] Amount made: 3.1 mg. LCMS m/z 550 [M+H] ⁺ , purity (UV/MS) 95/70.

N-f3-chlorobenzyn-7-methoxy-l-(3-(2-phenoxyethylamino ^* )propyl>l H-indole-3- carboxamide C220

[0659] Amount made: 3.7 mg. LCMS m/z 492 [M+H] ⁺ , purity (UV/MS) 96/70.

N-(3-chlorobenzylV7-methoxy-l-('3-( ^' 3-('2-oxo-2-phenylethylV8-azabicvclor3.2.11octan-8- vDpropylVl H-indole-3-carboxamide C221

[0660] Amount made: 3.5 mg. LCMS m/z 584 [M+H] ⁺ , purity (UV/MS) 95/80.

N-(3-chlorobenzyl)-7-methoxy-l-(3-(3-pentyl-8-azabicyclo[3.2 .noctan-8-yl ^' )propyl)-lH- indole-3-carboxamide C222

[0661] Amount made: 3.5 mg. LCMS m/z 536 [M+H] ⁺ , purity (UV/MS) 95/90.

N-(3-chlorobenzvπ-7-methoxy-l-(3-(3-phenethyl-8-azabicvc lor3.2.noctan-8-vπpropylVlH- indole-3-carboxamide C223

[0662] Amount made: 5.5 mg. LCMS m/z 570 [M+H] ⁺ , purity (UV/MS) 93/80.

N-('3-chlorobenzyl')-7-methoxy-l-f3-(4-(2-methoxyphenyl ^' )piperidin-l-vπpropylVlH-indole- 3-carboxamide C224

[0663] Amount made: 4.0 mg. LCMS m/z 546 [M+H] ⁺ , purity (UV/MS) 96/80.

N-(3-chlorobenzylV7-methoxγ-l-(3-( ^' 4-( ^' 2-oxoindolin-1-vπpiperidin-l -yl)propyl)-lH-indole- 3-carboxamide C225

[0664] Amount made: 1 .1 mg. LCMS m/z 571 [M+H] ⁺ , purity (UV/MS) 97/90.

N-(3-chlorobenzyl ^' )-7-methoxy-l-(3-(4-r2-phenoxyethvDpiperazin-l-yl)propyl ^' )-l H-indole-3- carboxamide C226

[0665] Amount made: 7.6 mg. LCMS m/z 561 [M+H] ⁺ , purity (UV/MS) 100/100.

N-π-chlorobenzyπ-y-methoxy-l-π-r^O-fpyridin-S-ylVKZ^-o xadiazol-S-yπpiperidin-I- yOpropyIVl H-indole-3-carboxamide C227

[0666] Amount made: 5.6 mg. LCMS m/z 585 [M+H] ⁺ ₅ purity (UV/MS) 98/60.

N-(3-chlorobenzvπ-7-methoxy-l-('3-r4-(3-(pyridin-4-ylVl, 2,4-oxadiazol-5-vπpiperidin-l- y Qpropyl V 1 H-indole-3 -carboxamide C228

[0667] Amount made: 6.8 mg. LCMS m/z 585 [M+H]\ purity (UV/MS) 98/60.

N-(3-chlorobenzvπ-7-methoxy-l-(3-( ^' 4-oxospirofchroman-2.4'-piperidine1-r-yl ^' )propyl ^' )-lH- indole-3 -carboxamide C229

[0668] Amount made: 6.1 mg. LCMS m/z 572 [M+H] ⁺ , purity (UV/MS) 100/90.

N-fS-chlorobenzvπ^-methoxy-l-π-^-phenethyl-lλ-diazepan -l-vπpropylVl H-indole-S- carboxamide C230

[0669] Amount made: 6.3 mg. LCMS m/z 559 [M+H] ⁺ , purity (UV/MS) 100/90.

N-benzyl-l-G-(πR.3r.5S ^' )-3-( ^' 2-<'3.4-dichlorophenylV2-oxoethyl>-8-azabicvclor3.2.no ctan- 8-yl)propylV7-ethyl-lH-indole-3-carboxamide C231

[0670] Amount made: 4.8 mg. LCMS m/z 616 [M+H] ⁺ , purity (UV/MS) 93/40.

N-benzyl-l-f3-fdR.3r.5SV3-r2-f4-chlorophenvn-2-oxoethyn-8 -azabicvclor3.2.11octan-8- vDpropyl)-7-ethyl- 1 H-indole-3-carboxamide C232

[0671] Amount made: 4.5 mg. LCMS m/z 582 [M+H] ⁺ , purity (UV/MS) 99/80.

N-ben2υl-l-f3-('4-r2-r4-chloronaphthalen-l-yloxy)ethyl)pipe razin-l-yl)propyl ^' )-7-ethyl-lH- indole-3-carboxamide C233

[0672] Amount made: 4.4 mg. LCMS m/z 609 [M+H] ⁺ , purity (UV/MS) 100/90.

N-ben2^1-7-ethyl-l-r3-rnR.3r.5SV3-f2-oxo-2-(pyridin-2-yne thyl>-8-azabicyclor3.2.noctan- 8-yπpropyl)- 1 H-indole-3-carboxamide C234

[0673] Amount made: 2.4 mg. LCMS m/z 549 [M+H] ⁺ , purity (UV/MS) 100/100.

W

N-benzyl-7-ethyI- 1 -(3-(4-r2-moφholino-2-oxoethyl')piperazin- 1 -vOpropylV 1 H-indole-3- carboxamide C235

[0674] Amount made: 9.8 mg. LCMS m/z 532 [M+H] ⁺ , purity (UV/MS) 100/80.

N-benzyl-7-ethyl-l-(3-(4-('2-phenoxyethyl)piperazin-l-yπ propylVlH-indole-3-carboxamide C236

[0675] ^' Amount made: 6.1 mg. LCMS m/z 525 [M+H] ⁺ , purity (UV/MS) 100/90.

N-benzyl-7-ethyl-l-(3-(4-( ^' 3-phenoxypropyl)-l,4-diazepan-l-yπpropylVlH-indole-3- carboxamide C237

[0676] Amount made: 3.0 mg. LCMS m/z 553 [M+H] ⁺ , purity (UV/MS) 100/100.

N-benzyl-7-ethyl- 1 -(3-f4-phenethyl- 1 ,4-diazepan- 1 -y BpropyQ- 1 H-indole-3-carboxamide C238

[0677] Amount made: 5.3 mg. LCMS m/z 523 [M+H] ⁺ , purity (UV/MS) 98/80.

N-isobutyl-7-methoxy-l -(3-(2-phenoxyethylamino)propyl>l H-indole-3-carboxamide C239 [0678] Amount made: 4.7 mg. LCMS m/z 424 [M+H] ⁺ , purity (UV/MS) 95/80.

N-isobutyl-7-methoxy-l-(3-('3-r2-oxo-2-phenylethyl)-8-aza bicyclo[3.2.1]octan-8-vπpropyl>- 1 H-indole-3 -carboxami de C240

[0679] Amount made: 4.0 mg. LCMS m/z 516 [M+H] ⁺ , purity (UV/MS) 98/80.

N-isobutyl-7-methoxy-l-( ^' 3-(3-pentyl-8-azabicvclof3.2.1]octan-8-yl)propyl)-3H-indole- 3- carboxamide C241

[0680] Amount made: 2.1 mg. LCMS m/z 468 [M+H] ⁺ , purity (UV/MS) 87/80.

N-isobutyl^-methoxy-l-Q-D-phenethyl-S-azabicyclorS.σ.1]o ctan-S-yDpropylVl H-indole-3- carboxamide C242

[0681] Amount made: 4.1 mg. LCMS m/z 502 [M+H] ⁺ , purity (UV/MS) 90/70.

N-isobutyl-7-methoxy-l-(3-r4-( ^' 2-methoxyphenyπpiperidin-l-yl')propyl>lH-indole-3- carboxamide C243

[0682] Amount made: 2.2 mg. LCMS m/z 478 [M+H] ⁺ , purity (UV/MS) 96/70.

N-isobutyl-7-methoxy- 1 -(3 -f 4-(2-phenoxyethyl)piperazin-l -yl)propyl>- 1 H-indole-3- carboxamide C244

[0683] Amount made: 9.0 mg. LCMS m/z 493 [M+H] ⁺ , purity (UV/MS) 94/70.

N-isobutyl-7-memoxy-l-f3-f4-(3-(pyridin-3-yiyi ,2,4-oxadiazol-5-yOpiperidin-l-yl)propyl>- 1 H-indole-3 -carboxamide C245

[0684] Amount made: 6.0 mg. LCMS m/z 517 [M-HH] ⁺ , purity (UV/MS) 99/70.

N-isobutyl-7-methoxy- 1 -(3 -f 4-(3-(pyridin-4-y IV 1 ,2,4-oxadiazol-5-yDpiperidin- 1 -vPpropy 1 V- lH-indole-3-carboxamide C246

[0685] Amount made: 6.9 mg. LCMS m/z 517 [M+H] ⁺ , purity (UV/MS) 97/60.

N-isobutyl-7-methoxy-l-( ^' 3-r4-oxospirorchroman-2,4'-piperidine]-r-yl)propyl>-l H-indole-3- carboxamide C247

[0686] Amount made: 6.3 mg. LCMS m/z 504 [M+H] ⁺ , purity (UV/MS) 100/90.

N-isobutyl-7-methoxy-l-( ^r 3-('4-phenethyl-l,4-diazepan-l-yl)propyl>lH-indole-3- carboxamide C248

[0687] Amount made: 6.8 mg. LCMS m/z 491 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3-(4-f 3-cyanopyridin-2-yπ- 1 ,4-diazepan- 1 -vDpropy P-N-(2-ethylhexyl V 1 H-indole-3- carboxamide C249

[0688] Amount made: 9.3 mg. LCMS m/z 515 [M+H]\ purity (UV/MS) 97/75.

1 -(3-(4-(3-cyanopyridin-2-yl>l ^-diazepan-l-yDpropylVN-O-methylbenzylVl H-indole-3- carboxamide C250

[0689] Amount made: 7.5 mg. LCMS m/z 507 [M+H] ⁺ ₅ purity (UV/MS) 95/66.

l-(3-f4-('3-cvanopyridin-2-ylV1.4-diazepan-l-yl ^' )propyl>N-isobυtyl-lH-indole-3- carboxamide C251

[0690] Amount made: 5.1 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 96/77.

1 -(3-(4-r4-chlorophenylthio ^' )piperidin-l -yl)propylVN-(2-ethylhexyl ^' )-l H-indole-3- carboxamide hydrochloride C252

[0691] Amount made: 4.3 mg. LCMS m/z 540 [M+H] ⁺ , purity (UV/MS) 90/60.

l-G-(4-f4-chlorophenylthio)piperidin-l-yl)propyl>N-(3-met hylbenzyl ^' )-lH-indole-3- carboxamide C253

[0692] Amount made: 10.2 mg. LCMS m/z 532 [M+H] ⁺ , purity (UV/MS) 100/63.

1 -(3-(4-(4-chlorophenylthio)piperidin- 1 -vDpropylVN-isobutyl- 1 H-indole-3 -carboxamide hydrochloride C254

[0693] Amount made: 1.3 mg. LCMS m/z 484 [M+H] ⁺ , purity (UV/MS) 75/54.

l-(3-(4-r4-fluorophenoxy)piperidin-l-yπpropyl)-N-(3-meth ylben2rylVlH-indole-3- carboxamide C255

[0694] Amount made: 7.9 mg. LCMS m/z 500 [M+H] ⁺ , purity (UV/MS) 95/100.

l-(3-(4-(4-fluorophenoxy)piperidin-l-yl)propylVN-isobutyl -lH-indoIe-3-carboxamide hydrochloride C256

[0695] Amount made: 3.9 mg. LCMS m/z 452 [M+H] ⁺ , purity (UV/MS) 81/58.

l-D-M-^enzofdlthiazol^-yDpiperidin-l-yDpropylVN-Q-chlorob enzyD-lH-indole-S- carboxamide C257

[0696] Amount made: 5.3 mg. LCMS m/z 543 [M+H] ⁺ , purity (UV/MS) 96/66.

l-(3-(4-(benzord1thiazol-2-vnpiperidin-l-yl)propylVN-('2- ethylheχylVlH-indole-3- carboxamide C258

[0697] Amount made: 7.2 mg. LCMS m/z 531 [M+H] ⁺ , purity (UV/MS) 91/62.

l-CS-^-rbenzofdithiazol-Z-yπpiperidin-l-yπpropylVN-O-ch lorobenzyD-lH-indole-B- carboxamide C259

[06981 Amount made: 5.0 mg. LCMS m/z 543 [M+H]\ purity (UV/MS) 100/93.

l-CS-f^Cbenzofd^thiazol^-yπpiperidin-l-yπpropylVN-fS-me thylbenzylVlH-indole-S- carboxamide C260

[0699] Amount made: 4.9 mg. LCMS m/z 523 [M+H] ⁺ , purity (UV/MS) 91/66.

l -rS-K-Cbenzofd ^' lthiazol^-vπpiperidin-l-vπpropylVN^-chlorobenzvπ-lH-indol e-S- carboxamide C261

[0700] Amount made: 5.0 mg. LCMS m/z 543 [M+H] ⁺ , purity (UV/MS) 87/78.

l-f3-(4-(benzo[ ^" d]thiazol-2-yl)piperidin-l-vπpropyl)-N-isobutyl-lH-indole-3 -carboxamide C262

[0701] Amount made: 4.8 mg. LCMS m/z 475 [M+H] ⁺ , purity (UV/MS) 97/80.

l-r3-r4-benzylpiperidin-l-yl ^' )propyl>-N-(2-chlorobenzyl)-lH-indole-3-carboxamide C263 [0702] Amount made: 8.7 mg. LCMS m/z 500 [M+H] ⁺ , purity (UV/MS) 96/63.

l-r3-r4-benzylpiperidin-l-yl)propyl>N-(2-ethylhexyl> ;-lH-indole-3-carboxamide C264

[0703] Amount made: 8.3 mg. LCMS m/z 488 [M+H] ⁺ , purity (UV/MS) 92/70.

l-(3-(4-benzylpiperidin-l-yl)propylVN-(3-chlorobenzvπ-lH -indole-3-carboxamide C265

[0704] Amount made: 7.2 mg. LCMS m/z 500 [M+H] ⁺ , purity (UV/MS) 100/80.

l -f3-(4-benzylpiperidin-l-vπpropylVN-( ^' 3-methylbenzyl)-lH-indole-3-carboxamide C266 [0705] Amount made: 6.1 mg. LCMS m/z 480 [M+H] ⁺ , purity (UV/MS) 100/94.

1 -(3-(4-benzylpiperidin- 1 -y Opropy D-N-f 4-chlorobenzyD- 1 H-indole-3-carboxamide C267 [0706] Amount made: 8.2 mg. LCMS m/z 500 [M+H] ⁺ , purity (UV/MS) 98/67.

l-(3-(4-benzylpiperidin-l-yl)propylVN-isobutyl-lH-indole- 3-carboxamide C268

[0707] Amount made: 5.3 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 95/89.

1 -(3-f4-butylpiperidin- 1 -yl)propylVN-(2-chlorobenzylV 1 H-indole-3-carboxamide C269 [0708] Amount made: 8.5 mg. LCMS m/z 466 [M+Hf, purity (UV/MS) 66/57.

l -(3-(4-butylpiperidin-1-yQpropyl>N-f2-ethylhexyiyi H-indole-3-carboxamide C270

[0709] Amount made: 1 1.1 mg. LCMS m/z 454 [M+H] ⁺ , purity (UV/MS) 97/85.

l-O-^-butylpiperidin-l-ynpropyiyN-O-chlorobenzyl')-! H-indole-3-carboxamide C271 [0710] Amount made: 6.1 mg. LCMS m/z 466 [M+H] ⁺ , purity (UV/MS) 99/80.

l-(3-f4-bυtylpiperidin-l-yl)propyiyN-(3-methylbenzyl> l H-indole-3-carboxamide C272

[0711] Amount made: 10.2 mg. LCMS m/z 446 [M+H] ⁺ , purity (UV/MS) 100/89.

1 -(3-(4-butylpiperidin- 1 -y0propyiyN-(4-chlorobenzy I)-I H-indole-3-carboxamide C273 [0712] Amount made: 6.1 mg. LCMS m/z 466 [M+H] ⁺ , purity (UV/MS) 98/44.

1 -(3-(4-butylpiperidin- 1 -yOpropyl>N-isobutyl-l H-indole-3-carboxamide C274

[0713] Amount made: 5.4 mg. LCMS m/z 398 [M+H] ⁺ , purity (UV/MS) 100/83.

l-(3-(methyl( ^' 2-(pyridin-2-vπethyl ^' )amino)propyl>-N-( ^' 3-methylbenzylVlH-indole-3- carboxamide C275

[0714] Amount made: 9.3 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 95/82.

N-(2-chlorobenzylVl-(3-( ^' 2-phenylpropylamino)propylVl H-indole-3-carboxamide C276 {0715] Amount made: 4.2 mg. LCMS m/z 460 [M-HH] ⁺ , purity (UV/MS) 98/94.

N-Q-chlorobenzylVl-rS-rS-phenethyl-S-azabicyclorS^.noctan -S-vnpropylVlH-indole-S- carboxamide C277

[0716] Amount made: 8.6 mg. LCMS m/z 540 [M+H] ⁺ , purity (UV/MS) 85/30.

N-r2-chlorobenzyπ-l-(3-(4-(3-cyanopyridin-2-yπ-K4-diaze pan-l-vπpropyl)-lH-indoIe-3- carboxamide C278

[0717] Amount made: 9.1 mg. LCMS m/z 527 [M+H] ⁺ , purity (UV/MS) 96/63.

N-(2-chlorobenzylVl -f3-(4-(4-chlorophenylthio')piperidin-l-vπpropyl>-lH-ind ole-3- carboxamide C279

[0718] Amount made: 6.9 mg. LCMS m/z 552 [M+H] ⁺ , purity (UV/MS) 87/81.

N-(2-chloro benzyl)- 1 -(3 -(4-(4-fluorophenoxy)piperidin- 1 -yQpropy IV 1 H-indole-3- carboxamide C280

[0719] Amount made: 9.2 mg. LCMS m/z 520 [M+H] ⁺ , purity (UV/MS) 94/69.

N-(2-chlorobenzyl)-l -(3-r4-(pyrrolidin-l-vπpiperidin-l-yl ^' )propylVlH-indole-3-carboxamide C281

[0720] Amount made: 4.4 mg. LCMS m/z 479 [M+H] ⁺ , purity (UV/MS) 70/93.

N-(2-chlorobenzvπ-l-r3-(methyl( ^' 2-rpyridin-2-yl)ethvπamino)propyl')-lH-indole-3- carboxamide C282

[0721] Amount made: 15.0 mg. LCMS m/z 461 [M+H] ⁺ , purity (UV/MS) 86/82.

N-(2-ethylhexyπ-l-(3-(2-phenylpropylamino)propyl>-lH- indole-3-carboxamide C283

[0722] Amount made: 9.8 mg. LCMS m/z 448 [M+H] ⁺ , purity (UV/MS) 98/80.

N^-ethylhexylVl-fS-G-phenethyl-S-azabicvclorS.σ.lloctan- S-yl^propylVlH-indole-S- carboxamide C284

[0723] Amount made: 4.3 mg. LCMS m/z 528 [M+H] ⁺ , purity (UV/MS) 98/41.

N-(2-ethylhexylVl-G-( ^' 4-f4-fluorophenoxy')piperidin-l-yl ^' )propylVlH-indole-3-carboxamide hydrochloride C285

[0724] Amount made: 5.8 mg. LCMS m/z 508 [M+H] ⁺ , purity (UV/MS) 86/59.

N-(2-ethylhexyπ-l -(3-(4-(pyrrolidin-l-yl)piperidin-l-yl)propylVlH-indole-3-ca rboxamide C286

[0725] Amount made: 8.3 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 87/27.

N-Q-ethylhexylVl -O-rmethvKσ-Cpyridin-σ-vπethvπamino^propyIVlH-indole-S-c arboxamide C287

[0726] Amount made: 8.5 mg. LCMS m/z 449 [M-HH] ⁺ , purity (UV/MS) 93/80.

N-O-chlorobenzvπ-l-O-fZ-phenylpropylamino^propylVlH-indo le-3-carboxamide C288

[0727] Amount made: 1.5 mg. LCMS m/z 460 [M+H] ⁺ , purity (UV/MS) 100/96.

N-G-chlorobenzylVl-O-G-phenethyl-δ-azabicvclorS.σ.nocta n-8-vnpropylVlH-indole-B- carboxamide C289

[0728] Amount made: 4.3 mg. LCMS m/z 540 [M+H] ⁺ , purity (UV/MS) 94/82.

N-O-chlorobenzvπ-l -rS-^-π-cvanopyridin-l-ylVlλ-diazepan-l-yπpropylVlH-indol e-S- carboxamide C290

[0729] Amount made: 5.5 mg. LCMS m/z 527 [M+H] ⁺ , purity (UV/MS) 99/74.

N-r3-chloroben2yn-l -(3-( ^* 4-r4-chlorophenylthio)piperidin-l-yl)propyl>-l H-indole-3- carboxamide C291

[0730] Amount made: 2.6 mg. LCMS m/z 552 [M+H] ⁺ , purity (UV/MS) 91/72.

N-r3-chlorobenzylVl-(3-(4-(4-fluorophenoxy)piperidin-l-yl )propyl)-lH-indole-3- carboxamide C292

[0731] Amount made: 5.1 mg. LCMS m/z 520 [M+H] ⁺ , purity (UV/MS) 88/64.

N-O-chlorobenzylV 1 -(3-( ^" 4-(pyrrolidin- 1 -vPpiperidin-1 -y DpropylV 1 H-indole-3-carboxamide C293

[0732] Amount made: 5.2 mg. LCMS m/z 479 [M+H] ⁺ , purity (UV/MS) 94/88.

N-f3-chlorobenzyl)-l-(3-(methyl(2-(pyridin-2-yl ^' )ethvπamino)propγlVlH-indole-3- carboxamide C294

[0733] Amount made: 8.2 mg. LCMS m/z 461 [M+H] ⁺ , purity (UV/MS) 88/68.

N-(3-methγlbenzyl>l-(3-r2-phenylpropylamino)propylVl H-indole-3-carboxamide C295 [0734] Amount made: 3.1 mg. LCMS m/z 440 [M+H] ⁺ , purity (UV/MS) 99/94.

N-G-methylbenzylVl-fS-fS-phenethyl-S-azabicvclorS^. lloctan-S-vDDropylVlH-indole-B- carboxamide C296

[0735] Amount made: 8.6 mg. LCMS m/z 520 [M+H] ⁺ , purity (UV/MS) 93/80.

N-O-methylbenzylVl-D-K-Cpyrrolidin-l-vπpiperidin-l-vDpro pylVlH-indole-S-carboxamide C297

[0736] Amount made: 13.2 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 100/85.

N-^-chlorobenzylVl-O-^-phenylpropylamino^propylVlH-indole -S-carboxamide C298

[0737] Amount made: 2.9 mg. LCMS m/z 460 [M+H] ⁺ , purity (UV/MS) 100/97.

N-(4-chlorobenzyl')-l-(3-(3-phenethyl-8-azabicvclo| ^" 3.2.1]octan-8-vπpropylVlH-indole-3- carboxamide C299

' [0738] Amount made: 6.8 mg. LCMS m/z 540 [M+H] ⁺ , purity (UV/MS) 98/85.

N-(4-chlorobenzyl)-l-(3-(4-(3-cvanopyridin-2-yl ^' )-l,4-dia2epan-l-vDpropyl ^' )-lH-indole-3- carboxamide C300

[0739] Amount made: 8.2 mg. LCMS m/z 527 [M+H] ⁺ , purity (UV/MS) 73/64.

N-(4-chlorobenzylVl-( ^' 3-(4-( ^' 4-chlorophenylthio)piperidin-l-yl ^' )propyl>-lH-indole-3- carboxamide C301

[0740] Amount made: 6.5 mg. LCMS m/z 552 [M+H] ⁺ , purity (UV/MS) 80/68.

N-(4-chloroben2ryl)-l-(3-(4-(4-fluorophenoxy')piperidin-l -vπpropylVlH-indole-3- carboxamide C302

[0741] Amount made: 8.8 mg. LCMS m/z 520 [M+H] ⁺ , purity (UV/MS) 100/100.

N-(4-chlorobenzyl ^' )-l-( ^' 3-( ^' 4-(pyrrolidin-l-yl)piperidin-l-yl)propyl)-lH-indole-3-carbox amide C303

[0742] Amount made: 5.1 mg. LCMS m/z 479 [M+H] ⁺ , purity (UV/MS) 100/100.

N-(4-chlorobenzylVl-(3-( ^' methyl( ^' 2-( ^' pyridin-2-vπethyl')amino ^' )propyl)-lH-indole-3- carboxamide C3Q4

[0743] Amount made: 6.0 mg. LCMS m/z 461 [M+H] ⁺ , purity (UV/MS) 94/80.

N-isobutyl-1 -(3-(2-phenyrpropyIarnino)propyiy 1 H-indole-3-carboxamide C305

[0744] Amount made: 3.6 mg. LCMS m/z 392 [M+H] ⁺ , purity (UV/MS) 100/100.

N-isobutyl-l-O-rS-phenethyl-δ-azabicvclop^.1]octan-δ-y� �propylVlH-indole-S- carboxamide C306

[0745] Amount made: 4.8 mg. LCMS m/z 472 [M+H] ⁺ , purity (UV/MS) 85/75.

N-isobutyl-1 -(3-(4-(pyrrolidin-l-v0piperidin-l-yr)propyr)-l H-indole-3-carboxamide C307 [0746] Amount made: 4.4 mg. LCMS m/z 411 [M+H] ⁺ , purity (UV/MS) 93/30.

N-isobutyl-l-(3-( ^' methyir2-( ^' pyridin-2-yl)ethyπamino ^* )propyl>-l H-indole-3-carboxamide C308

[0747] Amount made: 6.8 mg. LCMS m/z 393 [M+H] ⁺ , purity (UV/MS) 91/66.

d-( ^' 3-(2,3-dihvdro-lH-inden-2-ylamino)propyl ^' )-7-methoxy-lH-indol-3- ylXphenyPmethanone C309

[0748] Amount made: 4.6 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 98/90.

(l-(3-(3-f2-chlorobenzyOpiperidin-l-yl)propyl>7-methox y-lH-indol-3- ylXcyclopropyPmethanone C310

[0749] Amount made: 13.2 mg. LCMS m/z 465 [M+H] ⁺ , purity (UV/MS) 100/90.

( 1 -(3-π-C2-chlorobenzy Dpiperidin- 1 -vPpropy IV 7-methoxy- 1 H-indoI-3-ylY phenvPmethanone C311

[0750] Amount made: 3.2 mg. LCMS m/z 501 [M+H] ⁺ , purity (UV/MS) 100/90.

(l-(3-r3-r2-chlorophenoxyV8-azabicyclof3.2.11octan-8-yl)p ropyl>-7-methoxy-lH-indol-3- yD(cyclopropyl)methanone C312

[0751] Amount made: 3.9 mg. LCMS m/z 493 [M+H] ⁺ , purity (UV/MS) 99/80.

(l-π-CS^-chlorophenethvn-δ-azabicvclorS^.1]octan-δ-vπ propyπ-T-methoxy-lH-indol-3- yl)(cyclopropyl)methanone C313

[0752] Amount made: 6.1 mg. LCMS m/z 505 [M+H] ⁺ , purity (UV/MS) 98/90.

(l-f3-(3-(4-chlorophenethylV8-azabicvclof3.2.1]octan-8-yl> ;propyl ^' )-7-methoxy-lH-indol-3- ylXphenvPmethanone C314

[0753] Amount made: 1.1 mg. LCMS m/z 541 [M+H] ⁺ , purity (UV/MS) 100/90.

(l-(3-( ^' 3-(4-chlorophenoxyV8-azabicvclo[3.2.11octan-8-yπpropyl ^' )-7-methoxy-lH-indol-3- vO(cyclopropyl)methanone C315

[0754] Amount made: 5.9 mg. LCMS m/z 493 [M+H] ⁺ , purity (UV/MS) 99/90.

d-(3-(3-(4-chlorophenoxy)-8-azabicyclor3.2.11octan-8-yl)p ropyl)-7-methoxy-lH-indol-3- ylXphenvPmethanone C316

[0755] Amount made: 5.4 mg. LCMS m/z 529 [M+H] ⁺ , purity (UV/MS) 80/60.

[0756] ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.04 - 7.98 (m, IH), 7.80 - 7.77 (m, 2H) ₅ 7.58 - 7.42 (m, 4H) ₃ 7.23 - 7.19 (m, 4H), 6.83 - 6.83 (m, 3H), 4.61 - 4.57 (m, 3H) ₅ 3.99 (s, 3H), 3.78 - 3.61 (m, 2H), 2.91 - 2.67 (m, 3H), 2.43 - 2.33 (m, 4H), 2.21 - 1.83 (m, 6H).

Cl -(3-(3 -(4-chlorophenoxy)piperidin- 1 -y 0propyl>7-methoxy- 1 H-indol-3 - ylVcyclopropyPmethanone C317

[0757] Amount made: 5.5 mg. LCMS m/z 467 [M+H]\ purity (UV/MS) 100/90.

π-(3-(3-(4-chlorophenoxy)piperidin-l-yl)propyl>7-meth oxy-lH-indol-3- yl)(phenyl)methanone C318

[0758] Amount made: 4.1 mg. LCMS m/z 503 [M+H] ⁺ , purity (UV/MS) 100/90.

fl -(3-( ^" 3-(4-fluorophenoxy)-8-azabicyclof3.2. noctan-8-yl)propylV7-methoxy-lH-indol-3- vDfphenvPmethanone C319

[0759] Amount made: 5.9 mg. LCMS m/z 513 [M+H] ⁺ , purity (UV/MS) 86/60.

(l-(3-(3-benzoyl-7-methoxy-lH-indol-l-yl)propyπpiperidin-4- yl)(phenvπmethanone C320 [0760} Amount made: 2.1 mg. LCMS m/z 481 [M+H] ⁺ ₅ purity (UVMS) 100/70.

(l -(3-C4-(2-(4-chloronaphthalen-l-yloxy ^' )ethvπpiperazin-l-vπpropyl>-7-methoxy-lH-indol-3- vO(cyclopropyl)methanone C321

[0761] Amount made: 1.4 mg. LCMS m/z 546 [M+H] ⁺ , purity (UV/MS) 100/100.

d-(3-(4-(2-(4-chlorophenoxy)ethvϊ)piperazin-l-vπpropylV 7-methoxy-lH-indol-3- yl)(cyclopropyl)methanone C322

[0762] Amount made: 8.2 mg. LCMS m/z 496 [M+H] ⁺ , purity (UV/MS) 97/80.

(l -(3-(4-(2-(4-chlorophenoxy)ethyl)piperazin-l-yl ^' )propyl ^' )-7-methoxy-lH-indol-3- yl)(phenyl)methanone C323

[0763] Amount made: 8.0 mg. LCMS m/z 532 [M+H] ⁺ , purity (UV/MS) 100/100.

(l-(3-(4-(2-(4-chlorophenoxy)ethyl)piperidin-l-yl ^' )propyl ^' )-7-methoxy-lH-indol-3- yl)(cyclopropyl)methanone C324

[0764] Amount made: 3.9 mg. LCMS m/z 495 [M+H] ⁺ , purity (UV/MS) 100/90.

(1 -f3-f4-(2-chIorobenzyD-l ,4-diazepan-l-vDpropyl>-7-methoxy-l H-indoI-3- yl)(cyclopropyl)methanone C325

[0765] Amount made: 3.8 mg. LCMS m/z 480 [M+H] ⁺ , purity (UV/MS) 98/80.

( 1 -f 3-(4-(2-chlorobenzvP- 1 ,4-diazepan- 1 -vDpropy l>7-methoχy- 1 H-indol-3 - ylVphenvDmethanone C326

[0766] Amount made: 5.9 mg. LCMS m/z 516 [M+H] ⁺ , purity (UV/MS) 98/90.

( 1 -(3-f4-(2-chlorophenoxy)piperidin-l -yl)propyl)-7-methoxy-l H-indol-3- yl)(cyclopropyl)methanone C327

[0767] Amount made: 3.0 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 94/70.

(l-f3-f4-f2-chlorophenoxy)piperidin-l-yl)propylV7-methoxy -lH-indol-3- yO(phenyl)methanone C328

{0768] Amount made: 8.6 mg. LCMS m/z 503 [M+H] ⁺ , purity (UV/MS) 92/50.

(l-r3-(4-(3-chlorophenoxy)piperidin-l-yl)propylV7-methoxy -lH-indol-3- yO(cvclopropyl)methanone C329

[0769] Amount made: 6.6 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 100/90.

π-f3-f4-(3-chlorophenoxy)piperidin-l-yl)propylV7-methoxy -lH-indol-3- yl)(phenvπmethanone C33Q

[0770] Amount made: 6.7 mg. LCMS m/z 503 [M+H] ⁺ , purity (UV/MS) 100/90.

( 1 -C3 -(4-f 4-chlorophenoxy ^' )piperidin- 1 -y l)propyl>-7-methoxy- ϊ H-indol-3- yO(cvclopropyl)methanone C331

[0771] Amount made: 4.4 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 97/80.

fl-O-f4-(4-chlorophenoxy)piperidin-l-yI)propyl>7-metho xy-lH-indol-3- yQCphenvPmethanone C332

[0772] Amount made: 6.3 mg. LCMS m/z 503 [M+H] ⁺ , purity (UV/MS) 80/50.

π-( ^" 3-r4-f4-fluorobenzyπ-I,4-diazepan-l-yl)propyl>-7-methoxy -lH-indol-3- vDfphenvQmethanone C333

[0773] Amount made: 6.4 mg. LCMS m/z 500 [M+H] ⁺ , purity (UV/MS) 100/90.

f 1 -(3 -(4-(4-fl uorophenoxy^piperidin- 1 -y Ppropyl V7-methoxy- 1 H-indol-3 - vOfphenyQmethanone C334

[0774] Amount made: 4.5 mg. LCMS m/z 487 [M+H] ⁺ , purity (UV/MS) 96/60.

π-f3-(4-(ben2θ| ^" d]thiazol-2-yl ^* )piperidin-l-vπpropylV7-methoxy-lH-indol-3- yPfcvclopropyOmethanone C335

[0775] Amount made: 3.7 mg. LCMS m/z 474 [M+H] ⁺ , purity (UV/MS) 95/70.

(l-(3-(4-(benzordlthiazoI-2-v0piperidin-l-vDpropyiy7-meth oxy-lH-indol-3- ylXphenvDmethanone C336

[0776] Amount made: 7.6 mg. LCMS m/z 510 [M+H] ⁺ , purity (UV/MS) 99/70.

(l-(3-(4-benzoylpiperidin-l-yl)propyl ^' )-7-methoxy-lH-indol-3-yl ^> )(cvclopropyπmethanone C337

[0777] Amount made: 3.7 mg. LCMS m/z 445 [M+Hf, purity (UV/MS) 97/70.

(l-(3-(4-butylpiperidin-l-vπpropylV7-methoxy-l H-indol-3-vπfcyclopropyl)methanone C338

[0778] Amount made: 5.1 mg. LCMS m/z 397 [M+H]\ purity (UV/MS) 100/90.

(l-(3-(4-butylpiperidin-l-vπpropylV7-methoxy-lH-indol-3-ylV phenyπmethanone C339 [0779] Amount made: 8.5 mg. LCMS m/z 433 [M+H] ⁺ , purity (UV/MS) 99/90.

(lR.5S)-8-f3-f3-acetyl-7-methoχy-lH-indol-l-vnpropylV8-a zabicyclor3.2.noctan-3-yl 3.4- dimethoxybenzoate C340

[0780] Amount made: 9.3 mg. LCMS m/z 521 [M+H] ⁺ , purity (UV/MS) 95/70.

(7-methoxy- 1 -(3-(2-phenoxyethylamino)propyl>- 1 H-indol-3-yl)(phenyl)methanone C341 [0781] Amount made: 2.6 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 98/80.

(7-methoχy-l -(3-(3-pentyl-8-azabicvclo[3.2.11octan-8-yπpropyl)-lH-indol -3- yl)(phenvDmethanone C342

[0782] Amount made: 3.1 mg. LCMS m/z 473 [M+H] ⁺ , purity (UV/MS) 92/92.

(7-methoxy- 1 -(3 -(4-(2-methoxypheny Dpiperidin- 1 -y Dpropy IV 1 H-indoI-3 - yl)(phenvπmethanone C343

[0783] Amount made: 7.7 mg. LCMS m/z 483 [M+H] ⁺ , purity (UV/MS) 95/70.

(7-methoxy-l-(3-(4-f2-phenoxyethyl)piperazin-l -yl ^* )propylVlH-indol-3- yl)(phenyl)methanone C344

[0784] Amount made: 7.5 mg. LCMS m/z 498 [M+H] ⁺ , purity (UV/MS) 100/90.

rT-methoxy-l-G-^-G-fpyridin-S-ylVl.σ^-oxadiazol-S-vnpipe ridin-l-vnpropylVlH-indol-3- vDfphenyQmethanone C345

[0785] Amount made: 6.1 mg. LCMS m/z 522 [M+H] ⁺ , purity (UWMS) 97/70.

(7-methoxy-l-(3-(4-(3-fpyridin-4-ylVl,2,4-oxadiazol-5-yl> piperidin-l -vI)propyl ^' )-lH-indol-3- yO(phenyDmethanone C346

[0786] Amount made: 8.4 mg. LCMS m/z 522 [M+H] ⁺ , purity (UV/MS) 95/60.

(7-methoxy-l -(3-(4-phenethyl- 1 ,4-diazepan-l -vDpropylV 1 H-indol-3-yP(pheny Dmethanone C347

[0787] Amount made: 7.0 mg. LCMS m/z 496 [M-HH] ⁺ , purity (UV/MS) 98/90.

l-(l-(3-(2,3-dihydro-lH-inden-2-ylamino)propyl')-7-ethyl-lH- indol-3-yl ^" )ethanone C348 [0788] Amount made: 2.3 mg. LCMS m/z 361 [M+H] ⁺ , purity (UV/MS) 99/90.

l-(l-(3-f2,3-dihvdro-lH-inden-2-ylamino ^> )propylV7-methoxy-lH-indol-3-yπ-2- phenylethanone C349

10789] Amount made: 1.8 mg. LCMS m/z 439 [M+H] ⁺ , purity (UV/MS) 99/80.

l-(l-(3-( ^' 2,3-dihydro-lH-inden-2-ylamino ^' )propyl ^* )-7-inethyl-lH-indol-3-yl ^' )ethanone C350 [0790] Amount made: 3.0 mg. LCMS m/z 347 [M+H] ⁺ , purity (UV/MS) 93/80.

l-(l-(3-r3-( ^" 2-chlorobenzyπpiperidin-l-yl)propyl ^' )-7-ethyl-lH-indol-3-yπethanone C351

[0791] Amount made: 2.4 mg. LCMS m/z 437 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-f3-(2-chlorobenzyl')piperidin-l-yπpropylV7-metho xy-lH-indol-3-yπ-2- phenylethanone C352

[0792] Amount made: 2.1 mg. LCMS m/z 515 purity (UV/MS) 98/90.

l-fl-r3-(3-(2-chlorobenzvπpiperidin-l-yπpropyl>-7-methy l-lH-indol-3-vπethanone C353 [0793] Amount made: 3.2 mg. LCMS m/z 423 [M+H] ^"1" , purity (UV/MS) 100/80.

1 -C 1 -( 3-G-(2-chlorobenzvDpyrrolidin- 1 -vP)propyl)-7-meth.yl- 1 H-indol-3-yl)ethanone C354 10794] Amount made: 0.4 mg. LCMS m/z 409 [MH-H] ⁺ , purity (UV/MS) 98/90.

l-π-(3-f3-f2-chlorophenoxyV8-a2abicvclof3.2.noctan-8-vnp ropylV7-ethyl-lH-indol-3- yl^ethanone C355

10795] Amount made: 2.0 mg. LCMS m/z 465 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -( 1 -(3-(3-(2-chlorophenoxyV8-azabicyclo| ^" 3.2.1 ]octan-8-vDpropyiy7-methoxy- 1 H-indol-3- yl)-2-phenyIethanone C356

[0796] Amount made: 3.1 mg. LCMS m/z 543 [M+H] ⁺ , purity (UV/MS) 100/90.

l -(l-(3-(3-(2-chlorophenoxyV8-azabicvclor3.2.11octan-8-yl> propylV7-methyl-lH-indol-3- vHethanone C357

[0797] Amount made: 0.3 mg. LCMS m/z 451 [M+H] ⁺ , purity (UV/MS) 99/90.

l-(l-f3-G-(4-chlorophenethvn-8-azabicvclo[3.2.noctan-8-yl >propylV7-ethyl-lH-indol-3- yQethanone C358

[0798] Amount made: 4.3 mg. LCMS m/z 477 [M+H] ⁺ , purity (UV/MS) 93/70.

l-(l-f3-(3-f4-chlorophenethylV8-a2abicyclor3.2.noctan-8-y npropylV7-methyl-lH-indol-3- vDethanone C359

[0799] Amount made: 2.8 mg. LCMS m/z 463 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-r3-(3-(4-chlorophenoxy)-8-azabicvclor3.2.1]octan-8-v πpropyl)-7-methyl-lH-indol-3- vPethanone C360

[0800] Amount made: 0.8 mg. LCMS m/z 451 [M+H] ⁺ , purity (UV/MS) 99/80.

l-d-(3-r3-f4-chlorophenoxy)piperidin-l-yπ-2-methylpropyl V7-methoxy-lH-indol-3- vDethanone C361

[0801] Amount made: 1.5 mg. LCMS m/z 455 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -f i -(3-(3-(4-chlorophenoxy)piperidin- 1 -y Dpropyl V7-ethyl- 1 H-indol-3-yl)ethanone C362

[0802] Amount made: 3.7 mg. LCMS m/z 439 [M+H] ⁺ , purity (UV/MS) 100/100.

l-d-O-O-C^chlorophenoxy^piperidin-l-y^propylVy-methoxy-lH -indol-3-ylVl- phenylethanone C363

[0803] Amount made: 2.7 mg. LCMS m/z 517 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(l-(3-f3-(4-chlorophenoxy ^' )piperidin-l-vπpropylV7-methyl-lH-indoI-3-yπethanone C364 [0804] Amount made: 2.2 mg. LCMS m/z 425 [M+H] ⁺ ₅ purity (UV/MS) 100/100.

l-(l-r3-(3-f4-fluorophenoxy ^* )-8-azabicvclo[3.2.11octan-8-ylV2-methylpropyl>-7-methoxy -lH- indol-3-vOethanone C365

[0805] Amount made: 0.6 mg. LCMS m/z 465 [M-I-H] ⁺ , purity (UV/MS) 79/60.

l-(l-(3-(3-('4-fluorophenoxyV8-a2abicvclo[3.2.1]octan-8-y l)propyl)-7-methoxy-lH-indol-3- yD-2-phenylethanone C366

[0806] Amount made: 5.2 mg. LCMS m/z 527 [M+H]\ purity (UV/MS) 92/80.

l-(l-(3-(3-(4-fluorophenoxyV8-azabicvclor3.2.11octan-8-vn propylV7-methyl-lH-indol-3- yPethanone C367

[0807] Amount made: 4.1 mg. LCMS m/z 435 [M+H] ⁺ , purity (UV/MS) 98/70.

l-(l-( ^" 3-(3-(4-fluorophenyl)-3-hydroxy-8-azabicvclo[3.2.1]octan-8-y l)propylV7-methoxy-lH- indol-3-vDethanone C368

[0808] Amount made: 8.9 mg. LCMS m/z 451 [M+Hf, purity (UV/MS) 98/70.

l-(l-f3-(3-( ^" cvclopropanecarbonyl)-7-methoxy-lH-indol-l-yl)propyl)piperid in-4-vπindolin-2- one C369

[0809] Amount made: 1.6 mg. LCMS m/z All [M+H] ⁺ , purity (UV/MS) 97/90.

l-(l-(3-(3-acetyl-7-bromo-lH-indol-l-yl)propyπpiperidin- 4-yl)indolin-2-one C370

[0810] Amount made: 2.8 mg. LCMS m/z 494 [M+H] ⁺ , purity (UV/MS) 96/90.

1 -(I -(3-(3-acetyl-7-bromo-2-methyl-lH-indol-l -v0propyQpiperidin-4-yl)indolin-2-one C371 [0811] Amount made: 0.6 mg. LCMS m/z 508 [M+H] ^4" , purity (UV/MS) 94/90.

l-d-(3-f3-acetyl-7-chloro-lH-indol-l-vπpropyπpiperidin- 4-yl)indolin-2-one C372

[0812] Amount made: 1.4 mg. LCMS m/z 450 [M+H] ⁺ , purity (UV/MS) 93/90.

1 -( 1 -f 3 -f 3-acetyl-7-ethyl- 1 H-indol- 1 -vDpropynpiperidin-4-vnindolin-2-one C373

[0813] Amount made: 0.5 mg. LCMS m/z 444 [M+H] ⁺ , purity (UV/MS) 90/90.

l -π-r3-(3-acetyl-7-methoxy-lH-indol"l -yl>propyl)piperidin-4-vπ-lH-benzofd ^" |imidazol- 2(3HVone C374

[0814] Amount made: 8.4 mg. LCMS m/z 447 [M+H] ⁺ , purity (UV/MS) 99/80.

l -d-(3-(3-acetyl-7-methyI-l H-indol- l-yl ^" )propyDpiperidin-4-yPindolin-2-one C375

[0815] Amount made: 1.9 mg. LCMS m/z 430 [M+H] ⁺ , purity (UV/MS) 87/90.

l-fl-( ^' 3-(4-(2-r4-chloronaphthalen-l-yloxy')ethyπpiperazin-l-vπ-2 -methylpropyl>-7-methoxy- lH-indol-3-yl)ethanone C376

[0816] Amount made: 0.2 mg. LCMS m/z 534 [M+H] ⁺ , purity (UV/MS) 100/90.

l-Cl-G-(4-(2-r4-chloronaphthalen-l-yloxy')ethvπpiperazin-l- vπpropyl ^' )-7-ethγl-lH-indol-3- vPethanone C377

[0817] Amount made: 1.6 mg. LCMS m/z 518 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -( 1 -(3 -(4-(2-(4-chloronaphthal en- 1 -yloxy ^' jethyPpiperazin- 1 -vDpropy lV7-methoxy- 1 H-indol - 3-yl)-2-phenylethanone C378

[0818] Amount made: 0.7 mg. LCMS m/z 596 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-( ^" 3-(4-( ^' 2-('4-chloronaphthalen-l-yloxy)ethvπpiperazin-l-yl ^' )propyl>-7-methyl-lH-indol-3- vDethanone C379

[0819] Amount made: 1.1 mg. LCMS m/z 504 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -Cl -(3-(4-(2-r4-chlorophenoxy)ethyl ^' )ρiperazin- 1 -yl)-2-methylpropyl>7-methoxy- 1 H-indol- 3-vHethanone C380

[0820] Amount made: 5.4 mg. LCMS m/z 484 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 1 -(3 -(4-(2-(4-chlorophenoxy)elhy Dpiperazin- 1 -vPpropyl V 7-ethy 1- 1 H-indol-3 -y Oethanone C381

[0821] Amount made: 7.9 mg. LCMS m/z 468 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 1 -O-^-Q-^-chlorophenoxy^ethvDpiperazin- 1 -vPpropylW-methpxy- 1 H-indol-3-y D-2- phenylethanone C382

[0822] Amount made: 5.6 mg. LCMS m/z 546 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-(4-(2-(4-chlorophenoxy)ethvQpiperazin-l-yl)propyi y7-methyl-lH-indol-3- vDethanone C383

[0823] Amount made: 5.3 mg. LCMS m/z 454 [M+H] ⁺ ₅ purity (UV/MS) 98/90.

1 -(I -(3-r4-(2-(4-chlorophenoxy)ethvPpiperidin-l -vI)-2-methylpropyl>7-methoxy-l H-indoI- 3-yl)ethanone C384

[0824] Amount made: 1.7 mg. LCMS m/z 483 [M+H] ⁺ , purity (UV/MS) 99/90.

l -(l-(3-(4-(2-(4-chlorophenoxy)ethyl)piperidin-l-yl)propylV7- ethyl-lH-indol-3-yl)ethanone C385

[0825] Amount made: 2.9 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 98/90.

1 -( 1 -(3 -(4-(2-(4-chlorophenoxy ^' )ethyl)piperidin- 1 -y l)propylV7-methoxy- 1 H-indol-3-yl)-2- phenylethanone C386

|0826] Amount made: 0.9 mg. LCMS m/z 545 [M+H] ⁺ ₅ purity (UV/MS) 97/90.

l-(l-(3-(4-(2-(4-chlorophenoxy)ethvπpiperidin-l-yl)propy lV7-methyl-lH-indol-3- vHethanone C387

[0827] Amount made: 2.9 mg. LCMS m/z 453 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-(4-(2,3-dichlorophenvπpiperazin-l-yl)propyl)-7-m ethoxy-lH-indol-3-yπethanone C388

[0828] Amount made: 1.8 mg. LCMS m/z 460 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 1 -(3-(4-(2,4-dichlorobenzy Dpiperazin- 1 -vπ-2-methylpropyl)-7-methoxy- 1 H-indol-3 - vHethanone C389

[0829] Amount made: 6.5 mg. LCMS m/z 488 [M+H] ⁺ , purity (UV/MS) 100/90.

l-π-(3-(4-(2,4-dichlorobenzyπpiperazin-l-vπpropylV7-ethyl -lH-indol-3-yl)ethanone C390 [0830] Amount made: 2.5 mg. LCMS m/z 472 [M+H] ⁺ , purity (UV/MS) 100/90.

l-Cl-(3-(4-(2,4-dichlorobenzvπpiperazin-l-yl)propyl>- 7-methoxy-lH-indol-3-yl')-2- phenylethanone C391

[0831] Amount made: 6.4 mg. LCMS m/z 550 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-(4-(2,4-dichlorobenzyl)piperazin-l-yl)propyl)-7-m ethyl-lH-indol-3-vπethanone C392

[0832] Amount made: 3.4 mg. LCMS m/z 458 [M+H] ⁺ , purity (UV/MS) 100/100.

l-π-(3-(4-(2,6-dimethylphenyl')piperazin-l-vπpropyl> -7-methoxy-lH-indol-3-yπethanone C393

[0833] Amount made: 9.2 mg. LCMS m/z 420 [M+H] ⁺ , purity (UV/MS) 97/60.

1 -(I -(3-(4-(2-chlorobenzyl)-l,4-diazepan-l-ylV2-methylpropyl ^' >-7-methoxy-l H-indol-3- vDethanone C394

[0834] Amount made: 4.0 mg. LCMS m/z 468 [M+H]\ purity (UV/MS) 99/90.

l-(l-(3-(4-(2-chlorobenzyl)-L4-diazepan-l-yπpropyl>7-eth yl-lH-indol-3-yl)ethanone C395 [0835] Amount made: 3.4 mg. LCMS m/z 452 [M+H] ⁺ , purity (UV/MS) 100/90.

1-(1 -(3-(4-(2-chlorobenzyiy 1.4-diazepan-l-yl)propylV7-methoxy-l H-indol-3-vD-2- phenylethanone C396

[0836] Amount made: 5.5 mg. LCMS m/z 530 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-(4-(2-chlorobenzyl)-l,4-diazepan-l-yl)propyl)-7-m ethyl-lH-indol-3-yl)ethanone C397

[0837] Amount made: 2.5 mg. LCMS m/z 438 [M+H] ⁺ , purity (UV/MS) 97/50.

1 -( 1 -(3 -( 4-(2-chlorophenoxy')piperidin- 1 -y l>propylV7-methyl- 1 H-indol-3 -yOethanone C398 [08381 Amount made: 6.2 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 1 -(3-f 4-(2-chlorophenyl)piperazin- 1 -vPpropy D-7-methoxy- 1 H-indol-3 -vQethanone C399 10839] Amount made: 2.2 mg. LCMS m/z 426 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -( 1 -(3-(4-(2-methoxyphenvQpiperidin- 1 -y Opropyl V7-methyl- 1 H-indol-3 -yOethanone C400 [0840] Amount made: 8.6 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 99/80.

l-π-fS-^-O-chloro-S-ftrifluoromethylipyridin^-vπpiperaz in-l-yπ^-methylpropyl)-?- methoxy- 1 H-indo 1-3 -vDethanone C401

[0841] Amount made: 5.4 mg. LCMS m/z 509 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -(I -G-^-O-chloro-S-ftrifluoromethyOpyridin^-yOpiperazin- 1 -yl)propyl)-7-ethyl- 1 H-indol- 3 -yOethanone C402

[0842] Amount made: 4.7 mg. LCMS m/z 493 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(l-(3-(4-(3-chloro-5-('trifluoromethyπpyπdin-2-yπpip erazin-l-yl)propyπ-7-methoxy-lH- indol-3-yO-2-phenylethanone C403

[0843] Amount made: 6.9 mg. LCMS m/z 571 [M+H] ⁺ , purity (UV/MS) 100/90.

l -(l-(3-(4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)piperazi n-l-yl)propyl ^' >-7-methoxy-lH- indol-3-yl)ethanone C404

[0844] Amount made: 8.0 mg. LCMS m/z 495 [M+H] ⁺ , purity (UV/MS) 98/90.

l-(l-(3-r4-(3-chloro-5-(trifluoromethyl)pyridin-2-yl ^' )piperazin-I-yl ^' )propyl)-7-methyl-l H- indol-3-yl)ethanone C405

[0845] Amount made: 6.2 mg. LCMS m/z 479 [M+H] ⁺ , purity (UV/MS) 98/80.

1 -( 1 -(3 -(4-(3 -chlorophenoxy^piperidin- 1 -vD-2-methylpropy lV7-methoxy- 1 H-indol-3 - vDethanone C406

[0846] Amount made: 2.7 mg. LCMS m/z 455 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-f3-(4-f3-chlorophenoxy)piperidin-l-yl ^* )propyl>-7-ethyl-lH-indol-3-yl ^' )ethanone C407

[0847] Amount made: 6.5 mg. LCMS m/z 439 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -(I -f3-(4-(3-chlorophenoxy')piperidin-l-yl>propyl>7-metho xy-l H-indol-3-vQ-2- phenylethanone C408

[0848] Amount made: 4.6 mg. LCMS m/z 517 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(l -(3-(4-f3-chlorophenoxy)piperidin-l-yl)propylV7-methyl-lH-in dol-3-vπethanone C409 [0849] Amount made: 4.5 mg, LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 100/100.

l-d -(3-(4-(4-chlorobenzyl)pipera2in-l-γl)propylV7-methoxy-l H-indol-3-yl)ethanone C410 [0850] Amount made: 9.8 mg. LCMS m/z 440 [M+H] ⁺ , purity (UV/MS) 100/70.

l-(l -(3-(4-(4-chlorophenoxy)piperidin-l-yl ^' )propyl ^' )-7-methyl-lH-indol-3-vπethanone C411 [0851] Amount made: 5.5 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 99/80.

l -( ^' l-r3-r4-(4-chlorophenylsulfonyl ^' )pipeπdin-l -yl ^' )propylV7-methoxy-lH-indol-3-vπethanone C412

[0852] Amount made: 3.6 mg. LCMS m/z 489 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 1 -C3-(4-( ^" 4-fluorobenzy P- 1 ,4-diazepan-l -v0propyl ^" )-7-methoxy- 1 H-indol-3-yl>2- phenylethanone C413

[0853] Amount made: 3.4 mg. LCMS m/z 514 [M+H] ⁺ , purity (UV/MS) 92/80.

l-π-r3-(4-r4-fluorobenzyπ-1.4-diazepan-l-yl>propylV7 -methyl-lH-indol-3-yπethanone C414

[0854] Amount made: 3.5 mg. LCMS m/z 422 [M+H] ⁺ , purity (UV/MS) 98/70.

1 -( 1 -(3-(4-f4-fluorophenoxy ^* )piperidin- 1 -yDpropyD-7-methyl- 1 H-indol-3-yPethanone C415 [0855] Amount made: 6.3 mg. LCMS m/z 409 [M+H] ⁺ , purity (UV/MS) 100/90.

[0856J ¹ H NMR (400 MHz ₅ CDCl ₃ ) δ 7.97 (d, IH, J= 8.0 Hz), 7.70 (s, IH), 7.17 (t, IH, J = 8 Hz), 6.95 (m, 2H), 6.84 (m, 2H), 6.71 (d, IH J = 7.8 Hz), 4.47 (t, 2H, J = 6.4 Hz), 4.24 (m, IH), 3.94 (s, 3H), 2.73 (m, IH), 2.49 (s, 3H), 2.32 (m, 4H), 2.05 (m, 4H), 1.84 (m, 2H).

l-(l-(3-( ^' 4-( ^' 4-fluorophenyl ^' )piperazin-l-vπpropyl')-7-methoxy-lH-indol-3-vπethanone C416 [0857] Amount made: 7.4 mg. LCMS m/z 410 [M+H] ⁺ , purity (UV/MS) 98/60.

l-(l-( ^" 3-(4-(benzord1thiazol-2-yl)piperidin-l-vπpropyl)-7-bromo-lH -indol-3-yπethanone C417

[0858] Amount made: 2.4 mg. LCMS m/z 496 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -( 1 -(3-(4-(benzord]thiazol-2-yPpiperidin- 1 -y Dpropyl >• 7-chloro- 1 H-indol-3 -vPethanone C418

[0859] Amount made: 3.9 mg. LCMS m/z 452 [M+H] ⁺ , purity (UV/MS) 92/80.

l-d-π-^-benzoylpiperidin-l-vπpropy^-bromo-lH-indol-3-yD ethanone C419

[0860] Amount made: 6.8 mg. LCMS m/z 467 [M+H]\ purity (UV/MS) 100/90.

l-π-(3-(4-benzoylpiperidin-l-yl)propylV7-chloro-lH-indol -3-yl)ethanone C420

[0861] Amount made: 3.6 mg. LCMS m/z 423 [M-I-H] ⁺ , purity (UV/MS) 96/70.

1 -f 1 -( 3-f 4-benzoylpiperidin- 1 -yl ^" )propyl)-7-methyl- 1 H-indol-3-y Oethanone C421

[0862] Amount made: 1.9 mg. LCMS m/z 403 [M+H] ⁺ , purity (UV/MS) 93/70.

l-(l-(3-(4-benzyl-4-hydroxypip6ridin-l-yl)propyl)-7-methoxy- lH-indol-3-yl')ethanone C422 [0863] Amount made: 8.4 mg. LCMS m/z 421 [M+H] ⁺ , purity (UV/MS) 99/90.

l-(l-(3-(4-bcnzylpiperidin-l-yl)propyi>-7-methoxy-lH-indo l-3-yl ^' )ethanone C423

[0864] Amount made: 7.4 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 100/90.

l -π-(3-f4-butylpiperidin-l-yDpropyl)-7-chloro-l H-indol-3-y Dethanone C424

[0865] Amount made: 2.0 mg. LCMS m/z 375 [M+H] ⁺ , purity (UV/MS) 100/90.

l-π-r3-f4-butylpiperidin-l-vπDropylV7-methyl-lH-indol-3 -yl)ethanone C425

[0866] Amount made: 5.0 mg. LCMS m/z 355 [M+H] ⁺ , purity (UV/MS) 99/90.

l-ri-r3-(7-methoxy-3-(2-phenylacetyl')-lH-indol-l-vπprop yπpiperidin-4-yl')indolin-2-one C426

[0867] Amount made: 1.4 mg. LCMS m/z 522 [M+H] ⁺ , purity (UV/MS) 96/90.

r-(3-r3-(cyclopropanecarbonyl>-7-methoxy-lH-indol-l-vπpr opyl)spiro| ^' chroman-2.4'- piperidin]-4-one C427

[0868] Amount made: 5.6 mg. LCMS m/z 473 [M+H] ⁺ , purity (UV/MS) 97/90.

r-(3-(3-acetyl-7-bromo-lH-indol-l-yl ^* )propyl)spirorchroman-2,4'-piperidin1-4-one C428

[0869] Amount made: 2.1 mg. LCMS m/z 495 [M+H] ⁺ , purity (UV/MS) 100/90.

r-rS-O-acetyl^-bromo-σ-methyl-lH-indol-l-vπpropyDspirof chroman^^'-piperidini^-one C429

[0870] Amount made: 1.3 mg. LCMS m/z 509 [M+H] ⁺ , purity (UV/MS) 100/100.

r-( ^" 3-(3-acetyl-7-chloro-lH-indol-l-vπpropyπspiro[chroman-2,4' -ρiperidin1-4-one C430

[0871] Amount made: 5.4 mg. LCMS m/z 451 [M+H] ⁺ , purity (UV/MS) 100/90.

l'-('3-( ^* 3-acetyl-7-ethyl-lH-indol-l-yl)propyl')spiro| ^' chroman-2.4'-piperidin1-4-one C431

[0872] Amount made: 4.6 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 100/90.

r-(3-(3-acetyl-7-methoxy-lH-indol-l-yl)-2-methylpropyπsp iro[chroman-2,4'-piperidinl-4- one C432

[0873] Amount made: 0.4 mg. LCMS m/z 461 [M+H] ⁺ , purity (UV/MS) 98/90.

l-(3-( ^" 3-acetyl-7-methoxy-lH-indol-l-yl)propyl)-4-phenylpiperidine- 4-carbonitrile C433 [0874] Amount made: 3.4 mg. LCMS m/z 416 [M+H] ⁺ , purity (UV/MS) 96/80.

l-(3-(3-acetyl-7-methoxy-lH-indol-l-yl ^> )propylVN.N-diethvIpiperidine-3-carboxamide C434 [0875] Amount made: 7.7 mg. LCMS m/z 414 [M+H] ⁺ , purity (UV/MS) 100/90.

1 '-(3-(3-acetyl-7-methyl-l H-indol-1 -vπpropyπspirorchroman-2,4'-piperidinl-4-one C435 [0876] Amount made: 2.8 mg. LCMS m/z 431 [M+H] ⁺ , purity (UV/MS) 100/90.

r-β-(3-benzoyl-7-methoxy-lH-indol-l-yl)propyπspirorchroman -2,4'-piperidin]-4-one C436 [0877] Amount made: 3.7 mg. LCMS m/z 509 [M+H] ⁺ , purity (UV/MS) 100/90.

r-(3-(7-methoxy-3-(2-phenylacetylVlH-indol-l-yl ^* )propyl)spirofchroman-2,4'-piperidin]-4- one C437

[0878] Amount made: 1.9 mg. LCMS m/z 523 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(4-chlorophenyl)-2-( ^' 8-( ^' 3-(3-(cyclopropanecarbonyl ^' )-7-methoxy- 1 H-indol- 1 -yl)propyl>8- azabicyclor3.2.11octan-3-yr)ethanone C438

[0879] Amount made: 6.0 mg. LCMS m/z 519 [M+H] ⁺ , purity (UV/MS) 98/80.

l-(4-chlorophenylV2-r8-f3-( ^' 7-methoxy-3-( ^' 2-phenylacetylVlH-indol-l-vnpropylV8- azabicycloβ.σ.lloctan-S-vDethanone C439

[0880] Amount made: 6.2 mg. LCMS m/z 569 [M+H] ⁺ , purity (UV/MS) 92/80.

1 -(7-bromo-l -(3-(2.3-dihvdro-lH-inden-2-ylamino')propylVlH-indol-3-yl)et hanone C440 [0881] Amount made: 4.1 mg. LCMS m/z 41 1 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-bromo- 1 -(3-f 2.3-dihvdro- 1 H-inden-2-ylamino ^> )propyl>-2-methyl- 1 H-indol-3-yl ^* )ethanone C441

[0882] Amount made: 2.1 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(7-bromo-l-f3-(2-phenoxyethylamino1propyiyiH-indoI-3-yD ethanone C442

[0883] Amount made: 3.7 mg. LCMS m/z 415 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(7-bromo-l-(3-('3-( ^' 2-chlorobenzyπpiρeridin-l-yl)propylVlH-indol-3-yl)ethanone C443 [0884] Amount made: 2.8 mg. LCMS m/z 487 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -(7-bromo- 1 -C3 -(3 -(2-chlorobenzyl)piperidin- 1 -v Dpropy 0-2 -methyl- 1 H-indol-3-vDethanone C444

[0885] Amount made: 0.9 mg. LCMS m/z 501 [M+H] ⁺ , purity (UV/MS) 98/90.

l-fy-bromo-l-π-π-fσ-chlorobenzvπpyrrolidin-l -yDpropylV∑-methyl-lH-indol-3- yPethanone C445

[0886] Amount made: 0.8 mg. LCMS m/z 487 [M+H] ⁺ , purity (UV/MS) 98/90.

l-(7-bromo-l -f3-r3-(2-chlorophenoxy)-8-azabicyclor3.2. lloctan-8-yl)propylVl H-indol-3- yDethanone C446

[0887] Amount made: 1.6 mg. LCMS m/z 515 [M+H] ⁺ , purity (UV/MS) 98/80.

l-(7-bromo-l -f3-π-( ^' 2-chlorophenoxyV8-azabicvclor3.2. noctan-8-yπpropyl ^' )-2-methyl-lH- indol-3-yl)ethanone C447

[0888] Amount made: 1.6 mg. LCMS m/z 529 [M+H] ⁺ , purity (UV/MS) 100/80.

l-(7-bromo-l-( ^' 3-( ^' 3-( ^' 4-chlorophenethylV8-azabicyclo[3.2.11octan-8-yl)propyl>-l H-indol-3- yDethanone C448

[0889] Amount made: 5.0 mg. LCMS m/z 527 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -(7-bromo-l -(3-(3-(4-chlorophenethyl)-8-azabicyclor3.2.11octan-8-yπpro pylV2-methyl-lH- indol-3-vOethanone C449

[0890] Amount made: 3.5 mg. LCMS m/z 541 [M+H] ⁺ , purity (UV/MS) 97/80.

l-(7-bromo-l -(3-(3-(4-chlorophenoxy)piperidin-l -v0propyiyiH-indol-3-yl)ethanone C450 [0891 ] Amount made: 3.1 mg. LCMS m/z 489 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-bromo- 1 -(3 -(3-(4-chlorophenoxy)piperidin- 1 -vPpropyl)-2-methy 1- 1 H-indol-3- yPethanone C451

[0892] Amount made: 0.4 mg. LCMS m/z 503 [M+H] ⁺ , purity (UV/MS) 100/70.

l-(7-bromo-l-(3-(3-r4-fluorQphenoxy>-8-a2abicvclop.2.1 ^" |octan-8-yl>propylVlH-indol-3- yPethanone C452

(0893] Amount made: 3.7 mg. LCMS m/z 499 [M+H] ⁺ , purity (UV/MS) 87/60.

l-(7-bromo-l-(3-(3-( ^' 4-fluorophenoxyV8-azabicvclo[3.2.11octan-8-yl)propyl ^' )-2-methyl-lH- indol-3-yl)ethanone C453

[0894] Amount made: 1.7 mg. LCMS m/z 513 [M+H] ⁺ , purity (UV/MS) 94/90.

l-(7-bromo-l-(3-(3-pentyl-8-azabicyclo[3.2.1 ^" )octan-8-yl)propylVlH-indol-3-vπethanone C454

[0895] Amount made: 2.6 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 91/80.

l-(7-bromo-l-(3-(3-phenethyl-8-azabicvclo| ^' 3.2.11octan-8-yl')propyl ^' )-lH-indol-3-vπethanone C455

[0896] Amount made: 3.9 mg. LCMS m/z 493 [M+H] ⁺ , purity (UV/MS) 85/70.

l-(7-bromo-l-(3-r4-(2-( ^' 4-chlorophenoxy)ethyl)piperazin-l-yπpropylVlH-indol-3- vPethanone C456

[0897] Amount made: 3.2 mg. LCMS m/z 518 [M+H]\ purity (UV/MS) 100/100.

1 -(7-bromo- 1 -(3 -(4-(2-(4-chlorophenoxy)ethy Dpiperazin- 1 -yl)propyl)-2-methv 1- 1 H-indol-3 - vPethanone C457

[0898] Amount made: 5.7 mg. LCMS m/z 532 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(7-bromo-l-(3-( ^" 4-r2-(4-chlorophenoxy)ethyπpiperidin-l-yπpropylV2-methyl-l H-indol-3- vHethanone C458

[0899] Amount made: 3.1 mg. LCMS m/z 531 [M+H]\ purity (UV/MS) 100/80.

1 -(7-bromo- 1 -(3-(4-(2-chlorobenzyl)- 1 ,4-diazepan- 1 -yDpropylV 1 H-indol-3-vDethanone C459

[0900] Amount made: 3.4 mg. LCMS m/z 502 [M+H] ⁺ , purity (UV/MS) 98/90.

l -f7-bromo-l-r3-(4-(2-chlorobenzyl ^* )-1.4-diazepan-l-yl)propyl>-2-methyl-lH-indol-3- yltethanone C460

[0901] Amount made: 3.3 mg. LCMS m/z 516 [M+H] ⁺ , purity (UVfMS) 98/90.

l-(7-bromo-l -(3-(4-(2-chlorophenoxy')piperidin-l-yl)propyl>-lH-indol- 3-yl ^' )ethanone C461 [0902] Amount made: 3.3 mg. LCMS m/z 489 [M+H] ⁺ , purity QJVIMS) 96/80.

1 -(7-bromo- 1 -(3-(4-(2-methoxyphenyl)piperidin- 1 -vDpropyl V 1 H-indol-3-yl)ethanone C462 [0903] Amount made: 5.4 mg. LCMS m/z 469 [M+H] ⁺ , purity (UV/MS) 95/60.

1 -(7-bromo- 1 -(3-(4-(2-phenoxyethyQpiperazin- 1 -yPpropylV 1 H-indol-3-vPethanone C463

[0904] Amount made: 8.8 mg. LCMS m/z 484 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -(7-bromo- l -(3-(4-(3-(pyridin-3-yr)-l.2,4-oxadiazol-5-yl)piperidin-l-y0 propylVlH-indol-3- yPethanone C464

[0905] Amount made: 8.0 mg. LCMS m/z 508 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-bromo- 1 -(3-(4-(3-(PVrJdJn^-VlVl.2,4-oxadiazol-5-yl)piperi din- l-yπpropylVl H-indol-3- yOethanone C465

[0906] Amount made: 0.6 mg. LCMS m/z 508 [M+H] ⁺ , purity (UV/MS) 100/70.

1 -(7-bromo- 1 -(3-(4-(3-chlorophenoxy ^' )piperidin- 1 -vOpropylV 1 H-indol-3-v0ethanone C466 [0907] Amount made: 5.9 mg. LCMS m/z 489 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-bromo- l-(3-(4-(3-chlorophenoxy)piperidin-l-yl ^' )propyl)-2-methy 1-1 H-indol-3- yPethanone C467

[0908] Amount made: 4.9 mg. LCMS m/z 503 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-bromo- 1 -(3-(4-(4-chlorophenoxy ^' )piperidin- 1 -vDpropy IV 1 H-indol-3-yl ^" )ethanone C468 [0909] Amount made: 4.6 mg. LCMS m/z 489 [M+H] ⁺ , purity (UV/MS) 94/80.

1 -(7-bromo- 1 -(3-(4-(4-fluorobenzvD-l ,4-diazepan-l -yPpropyl ^* )-! H-indol-3-vPethanone C469

[0910] Amount made: 4.4 mg. LCMS m/z 486 [M+H] ⁺ , purity (UV/MS) 96/70.

1 -(7-bromo- 1 -(3-(4-(4-fluorobenzyl')- 1 ,4-diazepan- 1 -yl)propylV2-methyl- 1 H-indol-3- vDethanone C470

10911} Amount made: 3.3 mg. LCMS m/z 500 [M+Hf, purity (UV/MS) 98/80.

1 -(7-bromo-l -(3-(4-butylpiperidm-l-yl)propylVlH-indol-3-yl)ethanone C471

[09121 Amount made: 4.9 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-bromo- l-(3-(4-phenethyl-l,4-diazepan-l -y PpropyD-lH-indol-3-yDethanone C472

[0913] Amount made: 6.2 mg. LCMS m/z 482 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-brorno-2-methyl-l -(3-(2-phenoxyethylamino ^' )propyl>-lH-indol-3-yl')ethanone C473

[0914] Amount made: 2.3 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 100/90.

yDethanone C474

{0915] Amount made: 3.0 mg. LCMS m/z 507 [M+H] ⁺ , purity (UV/MS) 95/80.

1 -(7-bromo-2-methyl- 1 -(3-(4-(2-phenoxyethyl)piperazin- 1 -vDpropyD- 1 H-indol-3- vPethanone C475

[0916] Amount made: 6.4 mg. LCMS m/z 498 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(7-bromo-2-methyl-l-(3-(4-(3-(pyridin-3-yl)-l ,2.4-oxadiazol-5-yl)piperidin-l-vπpropylV lH-indol-3-yl)ethanone C476

[0917] Amount made: 4.6 mg. LCMS m/z 522 [M+H] ⁺ , purity (UV/MS) 98/90.

l-(7-bromo-2-methyl-l-(3-( ^' 4-(3-(pyridin-4-yπ-l ,2.4-oxadiazol-5-yPpiperidin-l-yl ^' )propylV lH-indol-3-vOethanone C477

[0918] Amount made: 5.7 mg. LCMS m/z 522 [M+H] ⁺ , purity (UV/MS) 99/80.

l -(7-bromo-2-methyl-l-(3-(4-phenethyl-l,4-diazepan-l-vnpropyl VlH-indol-3-yl)ethanone C478

[0919] Amount made: 3.9 mg. LCMS m/z 496 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-chloro- 1 -(3-(2.3-dihydro-l H-inden-2-ylaminoVropylV 1 H-indol-3-y ltethanone C479 10920] Amount made: 3.0 mg. LCMS m/z 367 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-chloro- l-(3-(2-phenoxyethylamino)propyl>-l H-indol-3-yQethanone C480

[0921] Amount made: 2.5 mg. LCMS m/z 371 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-ChIQrQ- 1 -(3-(3 -f 2-chlorobenzvDpiperidin- 1 -y Opropyl)- 1 H-indoI-3-y Dethanone C481 [0922] Amount made: 3.6 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 100/70.

1 -(7-chloro- l-f3-(3-(2-chlorobenzyπpyrrolidin-l-yπpropylVlH-indol-3-y� �ethanone C482 [0923] Amount made: 1.0 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-chloro- l-(3-(3-(2-chlorophenoxy>8-azabicvclo[3.2.1 ]octan-8-yl)propylV lH-indol -3- vHethanone C483

[0924] Amount made: 2.3 mg. LCMS m/z Al 1 [M+H] ⁺ , purity (UV/MS) 100/80.

l-(7-chloro-l-(3-(3-(4-chlorophenethvn-8-azabicvclor3.2. πoctan-8-yl)propyl)-lH-indol-3- vDethanone C484

[0925] Amount made: 4.5 mg. LCMS m/z 483 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -(7-chloro- l-O-G-^-chlorophenoxyyS-azabicvcloB .2.1 ]octan-8-yDpropyl)-lH-indol-3- vPethanone C485

[0926] Amount made: 2.0 mg. LCMS m/z 471 [M+H] ⁺ , purity (UV/MS) 95/90.

1 -(7-chloro- l-(3-(3-(4-chlorophenoxy)piperidin-l -vDpropylMH-indol-3-yl)ethanone C486 [0927] Amount made: 4.0 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 100/100.

1 -f7-chloro-l -f 3-(3-f4-fluorophenoxyV8-azabicyclo[3.2. lloctan-8-vnpropylVl H-indoI-3- vDethanone C487

[0928] Amount made: 2.8 mg. LCMS m/z 455 [M+H] ⁺ , purity (UV/MS) 80/50.

l-fV-chloro-l-O-O-pentyl-S-azabicyclorS.σ.lloctan-S-vDpr opYlVlH-indol-3-yl)ethanone C488

10929] Amount made: 2.2 mg. LCMS m/z 415 [M+Hf, purity (UV/MS) 98/96.

l-fT-chloro-l-CB-O-phenethyl-δ-azabicvclofS^.l^octan-S-v πpropylVlH-indol-3-yl)ethanone C489

[0930] Amount made: 3.4 mg. LCMS m/z 449 [M+H] ⁺ , purity (UV/MS) 100/80.

l-(7-chloro-l-(3-(4-(2-(4-chlorophenoxy)ethyl')piperazin- l-yl)propylVlH-indol-3- vHethanone C490

[0931 ] Amount made: 6.1 mg. LCMS m/z 474 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(7-chloro-l-(3-(4-(2-(4-chlorophenoxy')ethyl ^' )piperidin-l-yl)propylVlH-indol-3-yl)ethanone C491

(0932] Amount made: 2.4 mg. LCMS m/z 473 [M+H] ⁺ , purity (UV/MS) 98/80.

1 -(7-chloro-l -(3-(4-(2-chlorobenzyl)-l ,4-diazepan-l -vDpropyl>-lH-indol-3-yl)ethanone C492

[0933] Amount made: 3.4 mg. LCMS m/z 458 [M+H] ⁺ , purity (UV/MS) 98/80.

l-f7-chloro-l -(3-(4-(2-chlorophenoxy)piperidin-l -yl)propyl>lH-indol-3-yDethanone C493 [0934] Amount made: 2.2 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 91/70.

l-(7-chloro-l-(3-(4-(2-methoxyphenyl)piperidin-l-yl)propylVl H-indol-3-yl)ethanone C494 [0935] Amount made: 3.1 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 95/70.

l-(7-chloro-l-(3-(4-(2-phenoxyethyl)piperazin-l-yl ^* )propyl)-lH-indol-3-yl)ethanone C495 [0936] Amount made: 7.5 mg. LCMS m/z 440 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(7-chloro- 1 -(3 -(4-G -(pyridin-3 -y IV 1 ,2.4-oxadiazol -5-vnpiperidin- 1 -y ^propyl V 1 H-indol-3- vHethanone C496

[0937] Amount made: 6.0 mg. LCMS m/z 464 [M-HH] ⁺ , purity (UV/MS) 98/80.

l-CT-chloro-l^^-O-fpyridin^-ylVl ^^-oxadiazol-S-vπpiperidin-l-vπpropylVlH-indol-3- vDethanone C497

[0938] Amount made: 8.3 mg. LCMS m/z 464 [MH-H] ⁺ , purity (UV/MS) 100/90.

1 -(7-chloro- 1 -(3-(4-(3-chlorophenoxy)piperidin- 1 -vOpropy IVl H-indol-3 -yPethanone C498 [0939] Amount made: 8.3 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -(7-chloro- 1 -(3-(4-(4-chlorophenoxy)piperidin- 1 -vDpropy IV 1 H-indol-3 -vPethanone C499 [0940] Amount made: 1.0 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 88/80.

1 -(7-chloro- 1 -(3-(4-(4-fluorobenzyl)-l ,4-diazepan- 1 -vDpropylV 1 H-indol-3-yl)ethanone C500

[0941] Amount made: 3.6 mg. LCMS m/z 442 [M+H] ⁺ , purity (UV/MS) 98/90.

l-(7-chloro-l-(3-(4-(4-fluorophenoxy)piperidin-l-yl)propyl') -lH-indol-3-yl)ethanone C501 [0942] Amount made: 3.7 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 90/80.

l-(7-chloro-l-(3-(4-phenethyl-l,4-diazepan-l-yl)propyl)-l H-indol-3-vI)ethanone C502

[0943] Amount made: 4.9 mg. LCMS m/z 438 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(7-ethyl-l-(3-(2-phenoxyethylamino)propyl)-lH-indol-3-y l)ethanone C503

[0944] Amount made: 2.3 mg. LCMS m/z 365 [M+H] ⁺ , purity (UV/MS) 99/90.

l-r7-ethyl-l-( ^r 3-r3-(4-fluorophenoxyV8-a2abicvclor3.2.11octan-8-vnpropylVlH -indol-3- vDethanone C504

[0945] Amount made: 1.9 mg. LCMS m/z 449 [M+H] ⁺ , purity (UV/MS) 98/70.

l-( ^" 7-ethyl-l-(3-(3-phenethyl-8-azabicvclof3.2.1 ^" )octan-8-yπpropylVlH-indol-3-vπethanone C505

10946] Amount made: 3.4 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 92/80.

1 -f 7-ethyl-l -(3-(4-(2-phenoxyethyDpiperazin- 1 -vDpropylV 1 H-indoI-3-yr)ethanone C506

[0947] Amount made: 8.8 mg. LCMS m/z 434 [M+H] ⁺ , purity (UV/MS) 100/90.

l-r7-ethyl-l-(3-(4-(3-rpyridin-3-ylV1.2,4-oxadia2θl-5-v� �piperidin-l-yl)propyl>lH-indol-3- vDethanone C507

[0948] Amount made: 2.4 mg. LCMS m/z 458 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 7-ethyl- 1 -(3-(4-G -f pyridin-4-yl)- 1.σλ-oxadiazol-S-ylipiperidin- 1 -vDpropylV 1 H-indol-3 - vDethanone C508

[0949] Amount made: 4.8 mg. LCMS m/z 458 [M+H] ⁺ , purity (UV/MS) 100/80.

l-r7-,ethyl-l -(3-( ^' 4-r4-fluorobenzylVK4-dia2epan-l-ynpropylVlH-indol-3-yl)ethan one C509 [0950] Amount made: 2.6 mg. LCMS m/z 436 [M+H] ⁺ , purity (UV/MS) 94/80.

1 -(7-ethyl- 1 -(3-(4-phenethyl- 1 ,4-diazepan- 1 -yOpropylV 1 H-indol-3-yQethanone C510

[0951] Amount made: 4.2 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 97/80.

1 -(7-methoxy- 1 -(2-methyl-3-(2-phenoxyethylamino)propy IV 1 H-indol-3-y Dethanone C511 [0952] Amount made: 0.3 mg. LCMS m/z 381 [M+H] ⁺ , purity (UV/MS) 98/90.

l-(7-methoxy-l-(2-methyl-3-( ^" 3-phenethyl-8-azabicvclo[3.2. l]octan-8-vπpropyl)-l H-indol-3- vPethanone C512

[0953] Amount made: 1.0 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 80/50.

1 -(7-methoxy- 1 -(2-methyl-3-(4-(2-phenoxyethyDpiperazin- 1 -vDpropylV 1 H-indol-3 - yDethanone C513

ϊ0954] Amount made: 5.8 mg. LCMS m/z 450 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(7-methoxy-l-f2-methyl-3-f4-f3-(pyridin-3-yl)-l,2.4-oxadia zol-5-yl ^* )piperidin-l-yl ^' )propyl ^' )- lH-indol-3-yl)ethanone C514

[0955] Amount made: 4.6 mg. LCMS m/z 474 [M+H] ⁺ , purity (UV/MS) 100/90.

l-fT-methoxy-l-fσ-methyl-S^-fS-rpyridin^-vπ-l^λ-oxadia zol-S-vπpiperidin-l-vπpropylV lH-indol-3-yl)ethanone C515

[0956] Amount made: 6.1 mg. LCMS m/z 474 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -f7-methoxy-l -(2-methyl-3-(4-phenethyl- 1.4-diazepan-l-yl ^* )propyiy 1 H-indol-3-vπethanone C516

[0957] Amount made: 3.5 mg. LCMS m/z 448 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -f 7 -methoxy- 1 -(3 -(2-phenoxyethylamino)propyl V 1 H-indol-3 -vO-2-phenv lethanone C517 [0958] Amount made: 2.9 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 99/70.

l -(7-methoxy-l-( ^' 3-(3-pentyl-8-azabicyclor3.2.11octan-8-vπpropyl')-l H-indol-3-yl')ethanone C518

[0959] Amount made: 7.1 mg. LCMS m/z 411 [M+H] ⁺ , purity (UV/MS) 97/80.

l ^-methoxy-l-rS-fS-phenethyl-S-azabicyclorS^.1]octan-8-vnDrop yD-lH-indol^-vn^- phenylethanone C519

[0960] Amount made: 3.6 mg. LCMS m/z 521 [M+H] ⁺ , purity (UV/MS) 96/90.

1 -(7-methoxy- 1 -( 3-(4-((tetrahvdrofuran-2-yl)methyl)piperazin- 1 -vDpropyP- 1 H-indol-3 - yPethanone C520

[0961] Amount made: 5.4 mg. LCMS m/z 400 [M+H] ⁺ , purity (UV/MS) 81/50.

1 -(7-methoxy- 1 -(3-f 4-C2-nitro-4-(trifluoromethyl)phenyl)piperazin- 1 -vPpropyl)- 1 H-indol-3- yDethanone C521

[0962] Amount made: 8.6 mg. LCMS m/z 505 [M+H] ⁺ , purity (UV/MS) 84/80.

l-r7-methoxy-l-(3-(4-(2-phenoxyethyl')piperazin-l-yπprop yl>-lH-indol-3-ylV2- phenylethanone C522

[0963] Amount made: 3.4 mg. LCMS m/z 512 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(7-methoxy-l-(3-(4-(3-(pyridin-3-vπ-h2,4-oxadiazol-5-v πpiperidin-l-vπpropylVlH-Sndol- 3-ylV2-phenylethanone C523

[0964] Amount made: 6.3 mg. LCMS m/z 536 [M+H] ⁺ , purity (UV/MS) 100/80.

l-(7-methoxy-l-( ^' 3-(4-( ^' 3-(pyridin-4-yl')-l ,2,4-oxadiazol-5-yl ^' )piperidin-l-yπpropy.l ^' )-lH-indol- 3-vD-2-phenylethanone C524

[0965] Amount made: 6.8 mg. LCMS m/z 536 [M+Hj ⁺ , purity (UV/MS) 99/80.

l-(7-methoxy-l-G-( ^' 4-f4-(trifluoromethyl)phenyl')piperazin-l-vπpropylVl H-indol-3- vDethanone C525

[0966] Amount made: 7.4 mg. LCMS m/z 460 [M+H] ⁺ , purity (UV/MS) 95/90.

l -r7-methoxy-l-(3-(4-morpholinopiperidin-l-yl)propylVlH-indol -3-yl ^* )ethanone C526

[0967] Amount made: 2.4 mg. LCMS m/z 400 [M+H] ⁺ ₅ purity (UV/MS) 89/60.

l -(7-methoxy-l-f3-foctahydroisoquinolin-2(lHVyOpropylMH-indol -3-yπethanone C527 [0968] Amount made: 8.4 mg. LCMS m/z 369 [M+H] ⁺ , purity (UV/MS) 99/90.

1 -(7-methyl-l -r3-(2-phenoxyethylamino')propylVl H-indol-3-vPethanone C528

[0969] Amount made: 3.3 mg. LCMS m/z 351 [M+H] ⁺ , purity (UV/MS) 100/90.

l-α-methyl-l-rS-G-pentyl-δ-azabicvclorS^. noctan-S-vnpropylVlH-indol-3-yπethanone C529

[0970] Amount made: 3.0 mg. LCMS m/z 395 [M+H] ⁺ , purity (UV/MS) 82/70.

l-(7-methyl-l-(3-(3-phenethyl-8-azabicyclor3.2.1]octan-8- yl)propyl)-lH-indol-3-yl)ethanone C530

[0971] Amount made: 3.5 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 98/90.

1 -f 7-methyl-l -f3-(4-(2-phenoxyethv0piperazin-l -vPpropylV 1 H-indol-3-yπethanone C531 [0972] Amount made: 4.8 mg. LCMS m/z 420 [M+H] ⁺ , purity (UV/MS) 100/90.

l -rT-methyl-l-fS-^-π-fDyridin-S-ylVl^λ-oxadiazol-S-vnpiDeri din-l-vnpropylVlH-indol-3- vOethanone C532

[0973] Amount made: 4.7 mg. LCMS m/z 444 [M+H] ⁺ , purity (UV/MS) 100/100.

l-r7-methyl-l-G-r4-(3-rpyridin-4-ylV1.2 _> 4-oxadiazol-5-vnpiperidin-l-vnproDylVlH-indol-3- vDethanone C533

[0974] Amount made: 5.3 mg. LCMS m/z 444 [M+H] ⁺ , purity (UV/MS) 100/90.

l^-methyl-l-π^-phenethyl-lλ-diazepan-l-vπpropylVlH-ind ol-3-yl)ethanone C534

[0975] Amount made: 5.1 mg. LCMS m/z 418 [M+H] ⁺ , purity (UV/MS) 97/70.

2-(4-(3-(3-acetyl-7-methoxy-lH-indol-l-vπpropyπpiperazi n-l-ylVl-morpholinoethanone C535

[0976] Amount made: 8.5 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 93/70.

2-( ^" 8-(3-(3-(cvclopropanecarbonylV7-methoxy-lH-indol-l -vπpropyl ^' )-8-

[0977] Amount made: 4.6 mg. LCMS m/z 485 [M+H] ⁺ , purity (UV/MS) 94/70.

2-('8-f3-f3-acetyl-7-bromo-lH-indol-l-vnpropylV8-azabicvc lo^3.2.noctan-3-vn-l-r4- chlorophenvPethanone C537

[0978] Amount made: 5.5 mg. LCMS m/z 541 [M+H] ⁺ , purity (UV/MS) 98/90.

2-(8-(3-(3-acetyl-7-bromo-lH-indol-l-ynpropylV8-azabicvcl or3.2.11octan-3-ylVl- phenylethanone C538

[0979] Amount made: 4.2 mg. LCMS m/z 507 [M+H] ⁺ , purity (UV/MS) 91/60.

' 2-(8-(3-(3-acetyl-7-bromo-2-methyl- 1 H-indol- 1 -vPpropylV 8-azabicyclo [3.2.11octan-3-y I)- 1 - (4-chlorophenyPethanone C539

[0980] Amount made: 3.9 mg. LCMS m/z 555 [M+H] ⁺ , purity (UV/MS) 98/70.

2-(8-(3-(3-acetyl-7-chloro-lH-indol-l-yl)t)ropylV8-azabic vclor3.2.11octan-3-ylVl-(4- chlorophenyDethanone C540

[0981] Amount made: 4.0 mg. LCMS m/z 497 [M+H] ⁺ , purity (UV/MS) 100/90.

l-fδ-O-π-acetyl-y-chloro-lH-indol-l-vnpropylVδ-azabicy clorS.σ.noctan-S-ylVl- phenylethanone C541

[0982] Amount made: 4.2 mg. LCMS m/z 463 [M+H] ⁺ , purity (UV/MS) 91/70.

2-(8-f3-(3-acetyl-7-ethyl-lH-indol-l-vnpropylV8-azabicvcl or3.2.noctan-3-ylVl-f4- chlorophenvDethanone C542

[0983] Amount made: 3.6 mg. LCMS m/z 491 [M+H] ⁺ , purity (UV/MS) 94/60.

2-r8-(3-(3-acetyl-7-methoxy-lH-indol-l-yl ^' )-2-rnethylpropylV8-a2abicvcIor3.2.11octan-3-yl)- l-f4-chlorophenvπethanone C543

[0984] Amount made: 5.1 mg. LCMS m/z 507 [M+H] ⁺ , purity (UV/MS) 96/90.

2-(8-(3 -f 3 -acety I-7-methyl- 1 H-indol- 1 -yl)ρropylV8-azabicvclor3.2.1 ^" loctan-3-y IV 1 -(4- chlorophenvDethanone C544

[0985] Amount made: 3.3 mg. LCMS m/z 477 [M+H] ⁺ , purity (UV/MS) 98/70.

2-(8-r3-(3-acetyl-7-methyl-lH-indol-l-vnpropylV8-azabicyc lor3.2.11octan-3-ylVl- phenylethanone C545

[0986] Amount made: 2.1 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 99/80.

2-(8-r3-(3-benzoyl-7-methoxy-lH-indol-l-vnpropylV8-azabic vclor3.2.11octan-3-yn-l-(4- chlorophenyQethanone C546

[0987] Amount made: 7.0 mg. LCMS m/z 555 [M+H] ⁺ , purity (UV/MS) 96/70.

σ^δ-fS-O-benzoyl^-methoxy-lH-indol-l-vnpropylVS-azabicv clorS^.l ioctan-S-vn-l- phenylethanone C547

[0988] Amount made: 5.7 mg. LCMS m/z 521 [M+H] ⁺ , purity (UV/MS) 95/81.

3-acetyl-l-r3-r23-dihydro-lH-inden-2-ylamino')propylVlH-indo le-7-carbonitrile C548 [0989] Amount made: 3.0 mg. LCMS m/z 358 [M+H] ⁺ , purity (UV/MS) 99/80.

3-acetyl-l -G-( ^' 2-phenoxyethylamino ^* )propyl>-lH-indole-7-carbonitrile C549

[0990] Amount made: 3.7 mg. LCMS m/z ^' 362 [M+H] ⁺ , purity (UV/MS) 96/80.

S-acetyl-i -rS-π-^-^-chlorophenylV∑-oxoethylVS-azabicycloP^.1]octan- S-vπpropylVlH- indole-7-carbonitrile C550

[0991] Amount made: 5.1 mg. LCMS m/z 488 [M+H] ⁺ , purity (UV/MS) 95/80.

3 -acetyl- 1 -(3 -f 3 -( 2-chlorobenzyl)piperidin- 1 -y Ppropy 1>- 1 H-indole-7-carbonitri Ie C551

[0992] Amount made: 2.1 mg. LCMS m/z 434 [M+H] ⁺ , purity (UV/MS) 100/80.

3-acetyl-l-f3-('3-(2-chlorophenoxy)-8-azabicvclo[ ^' 3.2.1]octan-8-yl)propyl>-lH-indole-7- carbonitrile C552

[0993] Amount made: 3.3 mg. LCMS m/z 462 [M+H] ⁺ , purity (UV/MS) 94/100.

3-acetyl-l-(3-(3-(4-chlorophenoxy ^' )piperidin-l-yl)propyl>-lH-indole-7-carbonitrile C553

[0994] Amount made: 3.0 mg. LCMS m/z 436 [M+H] ⁺ , purity (UV/MS) 100/100.

3-acetyl-l-(3-r3-(4-fluorophenoxy ^' )-8-azabicvclo| ^' 3.2.1 ]octan-8-yl ^* )propylVlH-indole-7- carbonitrile C554

[0995] Amount made: 3.9 mg. LCMS m/z 446 [M+H] ⁺ , purity (UV/MS) 100/100.

3-acetyl-l-(3-(3-phenethyl-8-azabicyclo[3.2.11octan-8-yl ^* )propyl>-lH-indole-7-carbonitrile C555

[0996] Amount made: 2.8 mg. LCMS m/z 440 [M+H] ⁺ , purity (UV/MS) 92/90.

3 -acetyl- 1 -(3-(4-( ^" 2-(4-chloronaphthalen- 1 -yloxy)ethy Dpiperazin- 1 -vPpropy I)- 1 H-indole-7- carbonitrile C556

[0997] Amount made: 0.4 mg. LCMS m/z 515 [M+H] ⁺ , purity (UV/MS) 100/70.

3-acetyl-l-π-f4-f2-r4-chlorophenoxy)ethvπpiperazin-l-v� �propyl>-lH-indole-7-carbonitrile C557

[0998] Amount made: 7.2 mg. LCMS m/z 465 [M+H] ⁺ , purity (UWMS) 100/90.

3-acetyl-l-(3-(4-(2-(4-chlorophenoxy)ethyl)piperidin-l-yl >propyl>-lH-indole-7-carbonitrile C558

[0999] Amount made: 1.8 mg. LCMS m/z 464 [M+H] ⁺ , purity (UWMS) 100/90.

3-acetyl- 1 -(3-(4-f 2,4-dichlorobenzvDpiperazin- 1 -y Qpropy IV 1 H-indole-7-carbonitrile C559 [1000] Amount made: 6.4 mg. LCMS m/z 469 [M+H] ⁺ , purity (UWMS) 100/90.

3-acetyl-l-(3-(4-(2-chlorobenzv0-l ,4-diazepan-l -yl ^' )propyl ^' >-lH-indole-7-carbonitrile C560 [1001] Amount made: 2.9 mg. LCMS m/z 449 [M+H] ⁺ , purity (UV/MS) 69/60.

S-acetyl-l-π^-C∑-oxoindolin-l-vπpiperidin-l-vπpropylVl H-indole-7-carbonitrile C561 [1002] Amount made: 1.5 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 93/80.

3-acetyl-l-(3-(4-r2-phenoxyethvπpiperazin-l-yl)propyl ^' >-l H-indole-7-carbonitrile C562

[1003] Amount made: 7.1 mg. LCMS m/z 431 [M+H] ⁺ , purity (UV/MS) 100/90.

3-acetyl-l-(3-( ^' 4-r3-rpyridin-3-ylVl,2,4-oxadiazol-5-yπpiperidin-l-yπpropy l ^' )-lH-indole-7- carbonitrile C563

[1004] Amount made: 6.6 mg. LCMS m/z 455 [M+H] ⁺ , purity (UV/MS) 92/80.

3-acetyl- 1 -(3-f4-(3-(pyridin-4-yQ- 1 ^^-oxadiazol-S-vPpiperidin- 1 -yPpropylV 1 H-indole-7- carbonitrile C564

[1005] Amount made: 6.6 mg. LCMS m/z 455 [M+H] ⁺ , purity (UV/MS) 100/90.

3-acetyl- l-(3-r4-('3-chloro-5-rtrifluoromethyl ^' )pyridin-2-yl ^' )piperazin-l-yl ^' )propyl>l H-indole- 7-carbonitrile C565

[1006] Amount made: 6.7 mg. LCMS m/z 490 [M+H] ⁺ , purity (UV/MS) 100/90.

3 -acetyl- 1 -( 3 -C4-O -chlorophenoxy^piperidin- 1 -vDpropyl V 1 H-indole-7 _^ carbonitrile C566

[1007] Amount made: 5.6 mg. LCMS m/z 436 [M+H] ⁺ , purity (UV/MS) 100/100.

S-acetyl-l-CS-^-oxospirofchroman-σ^'-piperidinej-r-vπpr opylVlH-indole-T-carbonitrile C567

[1008] Amount made: 2.7 mg. LCMS m/z 442 [M+H] ⁺ , purity (UY/MS) 94/90.

3-acetyl-l-(3-(4-phenethyl-L4-diazepan-l-v0propylVlH-indo le-7-carbonitrile C568

[1009] Amount made: 4.7 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 80/80.

4-(4-f 3-(3 -acetyl-7-methoxy- 1 H-indol- 1 -vOpropyOpiperazin- 1 -y Pbenzonitrile C569

[1010] Amount made: 2.4 mg. LCMS m/z 417 [M+H] ⁺ , purity (UV/MS) 95/80.

cvclopropyl(l-(3-r2,3-dihydro-lH-inden-2-ylamino ^' )propyl>-7-methoxy-l H-indol-3- vDmethanone C570

[1011] Amount made: 4.8 mg. LCMS m/z 389 [M+H] ⁺ , purity (UV/MS) 97/80.

cvclopropyl(l-f ^' 3-(3-(4-fluorophenoxyV8-a2abicvclof3.2.11octan-8-yl')propyl& gt;7-methoxy-lH- indol-3 -vDmethanone C571

[1012] Amount made: 2.7 mg. LCMS m/z All [M+H] ⁺ , purity (UV/MS) 96/60.

cyclopropyl(l-( ^' 3-(4-(4-fluorobenzγl)-l,4-dia2epan-l-vπpropyl>-7-methox y-l H-indol-3- vDmethanone C572

[1013] Amount made: 5.0 mg. LCMS m/z 464 [M+H] ⁺ , purity (UV/MS) 100/90.

cyclopropyK 1 -f 3-(4-(4-fluorophenoxy)piperidin- 1 -yPpropylW-methoxy- 1 H-indol-3- vOmethanone C573

[1014] Amount made: 5.9 mg. LCMS m/z 451 [M+H] ⁺ , purity (UV/MS) 95/80.

cvclopropyl(7-methoxy-l-( ^' 3-(2-phenoxyethylamino)propyl>-lH-indol-3-vπmethanone C574 [1015] Amount made: 4.2 mg. LCMS m/z 393 [M+H] ⁺ , purity (UV/MS) 95/80.

cyclopropyl('7-methoxy-l-r3-f3-pentyl-8-azabicyclof3.2.1]oct an-8-vI')propyl ^' )-lH-indol-3- yPmethanone C575

[1016] Amount made: 2.4 mg. LCMS m/z 437 [M+H] ⁺ , purity (UV/MS) 86/80.

cvclopropyl(7-methoxy-l-r3-(3-phenethyl-8-azabicvclo[3.2. 1]octan-8-yl)propylVlH-indol-3- vDmethanone C576

[1017] Amount made: 5.4 mg. LCMS m/z 471 [M+H] ⁺ , purity (UV/MS) 83/60.

cyclopropyl(7-methoxy- 1 -(3-f4-(2-methoχyphenyl)piperidin-l -yDpropyP-l H-indol-3- yPmethanone C577

[1018] Amount made: 4.8 mg. LCMS m/z 447 [M+H] ⁺ , purity (UV/MS) 96/60.

cyclopropyl(7-methoxy-l-('3-(4-(2-phenoxyethyl')piperazin -l-yl')propyl>-l H-indol-3- yPmethanone C578

[1019] Amount made: 7.8 mg. LCMS m/z 462 [M+H] ⁺ , purity (UV/MS) 98/90.

cvclopropyir7-methoxy-l-(3-(4-(3-(pyπdin-3-vπ-l ,2,4-oxadia2θl-5-yl)piperidin-l-yl)propyl>- 1 H-indol-3-yl)methanone C579

[1020] Amount made: 6.0 mg. LCMS m/z 486 [M+H] ⁺ , purity (UV/MS) 100/90.

cyclopropyl(7-methoxy-l-( ^' 3-(4-(3-(pyridin-4-yl)-l,2,4-oxadiazol-5-yl)piperidin-l-vnpr opyl>- lH-indol-3-vDmethanone C580

[1021] Amount made: 7.7 mg. LCMS m/z 486 [M+H] ⁺ , purity (UV/MS) 99/90.

cyclopropyl(7-methoxy-l -C3-f4-phenethyl-l ,4-diazepan-l -yl)propyl)- 1 H-indol-3- yDmethanone C581

[1022] Amount made: 5.8 mg. LCMS m/z 460 [M+H] ⁺ , purity (UV/MS) 98/90.

ethyl l-(3-r3-acetyl-7-methoxy-lH-indol-l-yl)propyl)piperidine-4-c arboxylate C582

[1023] Amount made: 7.6 mg. LCMS m/z 387 [M+H] ⁺ , purity (UV/MS) 80/70.

1 -f 1 -( 2-r3-r4-fluorophenylV3-hvdroxy-8-azabicvclor3.2.1 loctan-8-vnethylV 1 H-indol-3 - vDethanone C583

[1024] Amount made: 2.8 mg. LCMS m/z 407 [M+H] ⁺ , purity (UWMS) 98/70.

l-fl-(2-r3-(cvclopropylmethoxyV8-azabicvcloj ^" 3.2.noctan-8-vnethylVlH-indol-3- yDethanone C584

[1025] Amount made: 6.0 mg. LCMS m/z 367 [M+H] ⁺ , purity (UWMS) 98/77.

l-n-f2-r4-f2-methoxyphenvI ^' )piperidin-l-vnethylVlH-indol-3-yl')ethanone C585

[1026] Amount made: 3.4 mg. LCMS m/z 377 [VH-H] ⁺ , purity (UV/MS) 100/87.

1 -( 1 -f 2-f 4-benzy lpiperidin- 1 -yliethylV 1 H-indol-3-yl)ethanone C586

[1027] Amount made: 1.0 mg. LCMS m/z 361 [M+H] ⁺ , purity (UV/MS) 100/70.

1 -( 1 -f 2-f 4-butylpiperidin- 1 -yHeth yl V 1 H-indo 1-3 -yltethanone C587

[1028] Amount made: 2.8 mg. LCMS m/z 327 [VH-H] ⁺ , purity (UV/MS) 100/91.

l-π-f2-f4-propoxypiperidin-l-yl)ethylVlH-indol-3-yl ^' )ethanone C588

[1029] Amount made: 1.8 mg. LCMS m/z 329 [VRH] ⁺ , purity (UV/MS) 100/90.

1 -Cl -f 2-hydroxy-3 -(4-( 1 -phenylethy Dpiperazin- 1 -vOpropyl V 1 H-indol-3-y Dethanone C589

[1030] Amount made: 1 1.5 mg. LCMS m/z 406 [M+H] ⁺ , purity (UV/MS) 100/70.

l-fl-(2-hydroxy-3-(4-propoxypiperidin-l-vπpropylVlI-I-in dol-3-yπethanone C590

[1031J Amount made: 5.0 mg. LCMS m/z 359 [VH-H] ⁺ , purity (UV/MS) 90/67.

l-(l-( ^' 2-methyl-3-(4-α-ρhenylethvπpiperazin-l-yπpropyl>-lH-i ndol-3-vπethanone C591 [1032] Amount made: 3.7 mg. LCMS m/z 404 [VH-H] ⁺ , purity (UV/MS) 98/55.

l-(l-(2-methyl-3-(4-proρoxypiperidin-l-yl ^' )propylVlH-indol-3-yl ^' )ethanone C592

[1033] Amount made: 3.0 mg. LCMS m/z 357 [VH-H] ⁺ , purity (UV/MS) 80/73.

l-(l-(3-(3-(2-methoxyethylV8-azabicvclof3.2.11octan-8-vπ propyl)-l H-indol-3-yl)ethanone C593

[1034] Amount made: 6.4 mg. LCMS m/z 369 [M+H] ⁺ , purity (UV/MS) 96/93.

l-π-G-G-^-chlorophenoxyVδ-azabicvclorS.σ.iloctan-δ-v� �propylVlH-indol-3-ylVσ.∑q- trifluoroethanone C594

[1035] Amount made: 2.8 mg. LCMS m/z 491 [M+H] ⁺ , purity (UV/MS) 98/64.

l-d-fS-O^-chlorophenoxyVS-azabicvclorS^.1]octan-8-vπprop ylVlH-indol-3-ylVS- methylbutan-1-one C595

[1036] Amount made! 3.4 mg. LCMS m/z 479 [M+H] ⁺ , purity (UV/MS) 100/84.

l-d-fS-π-^-chlorophenoxyVδ-azabicyclop^.l^octan-S-vπpr opylVlH-indol-3-yl)ethanone C596

[1037] Amount made: 16.0 mg. LCMS m/z 437 [M+H] ^"1" , purity (UV/MS) 95/72.

l-ri-(3-(3-f4-chlorophenoxyV8-azabicyclo[3.2.1]octan-8-yπpr opyl ^' )-lH-indol-3-vπethanone C597

[1038] Amount made: 16.0 mg. LCMS m/z 437 [M+H] ⁺ , purity (UV/MS) 97/64.

l-fl-(3-(3-r4-chlorophenoxyV8-azabicyclof3.2.noctan-8-yl ^' )propyl>-4-methoxy-lH-indol-3- vnethanone C598

[1039] Amount made: 2.1 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 79/39.

l-π-f3-(3-r4-chlorophenoxyV8-azabicyclor3.2.11octan-8-yl ^' )propyl>-5-methoxy-lH-indol-3- yltethanone C599

[1040] Amount made: 2.1 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 87/38.

l-(l-(3-r3-r4-chlorophenoxyV8-azabicvclor3.2.1]octan-8-v� �propylV5-methoxy-lH-indol-3- vDpentan-1-one C600

[1041] Amount made: 3.1 mg. LCMS m/z 509 [M+H] ⁺ , purity (UV/MS) 77/55.

l-d-(3-( ^' 3-( ^' 4-chlorophenoxyV8-azabicvclo| ^' 3.2.11octan-8-vπpropylV6-methoxy-lH-indol-3- yl~)ethanone C601

[1042] Amount made: 3.6 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 93/50.

l-d-π-CS^-fluorophenvD-S-hvdroxy-8-azabicvclorS.σ.1]oct an-S-vnpropylVlH-indol-3- yl)propan-l-one C602

[1043] Amount made: 3.3 mg. LCMS m/z 435 [M+H] ⁺ , purity (UV/MS) 98/80.

1 -(I -(3 -(3-(cyclopropylmethoxyV8-azabicyclor3.2.1 ^" loctan-8-yl>2-rnethylpropyO- 1 H-indol- 3-yl)ethanone C603

[1044] Amount made: 9.3 mg. LCMS m/z 395 [M+H] ⁺ , purity (UV/MS) 100/89.

l-d-O-O-fcyclopropylmethoxyVS-azabicyclop^.1]octan-8-vDpr opylVlH-indol-3-vπ-σ^^- trifluoroethanone C604

[1045] Amount made: 8.3 mg. LCMS m/z 435 [M+H] ⁺ , purity (UV/MS) 99/95.

l-(l-(3-(3-(cyclopropylmethoxyV8-azabicvclo[3.2.noctan-8- yl)propyl)-lH-indol-3-yπ-3- methylbutan-1-one C605

[1046] Amount made: 8.7 mg. LCMS m/z 423 [M+H] ⁺ , purity (UV/MS) 98/91.

1 -(I -(3-(3-(cyclopropylmethoxy>-8-azabicyclo| ^' 3.2. noctan-8-yπpropylVl H-indol-3- ypethanone C606

[1047] Amount made: 16.3 mg. LCMS m/z 381 [M+H] ⁺ , purity (UV/MS) 99/88.

l-d-G-rS^cyclopropylmethoxyVS-azabicyclo[3.2.1]ljoctan-δ -yπpropylVlH-indol-3- yppropan-l-one C607

[1048] Amount made: 5.6 mg. LCMS m/z 395 [M+H] ⁺ ₅ purity (UV/MS) 100/75.

l-π-f3-(3-rcyclopropylmethoxyV8-azabicyclo| ^' 3.2.noctan-8-yπpropylV4-methoxy-lH-indol- 3-yHethanone C608

[1049] Amount made: 4.7 mg. LCMS m/z 411 [M+H] ⁺ , purity (UV/MS) 99/81.

l-π-O-O-fcvclopropylmethoxyVδ-azabicvclol ^' S.σ.1]octan-8-vπpropylVS-methoxy-lH-indol- 3-yl)ethanone C609

[1050] Amount made: 4.1 rag. LCMS m/z 41 1 [M+H] ⁺ , purity (UV/MS) 100/86.

l -Cl-O-O-CcvclopropylmethoxyVS-azabicvclop^.1]octan-8-yliprop ylVS-methoxy-lH-indol- 3-yDpentan-l-one C610

[1051] Amount made: 4.8 mg. LCMS m/z 453 [M+H] ⁺ , purity (UV/MS) 99/71.

l-π-rS-rS-rcvclopropylmethoxyVS-azabicvcIop.σ.1]octan-S -vπpropylVθ-methoxy-lH-indol- 3-vDethanone C611

[1052] Amount made: 10.5 mg. LCMS m/z 41 1 [M+H] ⁺ , purity (UV/MS) 100/93.

l-d-π-G^-dihydroisoquinolin-∑πHVvDpropyD-lH-indol-3-y l)ethanone C612

[1053] Amount made: 12.0 mg. LCMS m/z 333 [MH-H] ⁺ , purity (UV/MS) 88/60.

l-π-O-O-butyl-S.S-diazabicvcloCS.σ.1]octan-8-vπpropylV lH-indol-3-yl)ethanone C613

[1054] Amount made: 18.1 mg. LCMS m/z 368 [M+H] ⁺ , purity (UV/MS) 95/61.

l -d-O-rS-pentyl-8-azabicvcloP^Jloctan-8-vπpropylVlH-indol-3- vDethanone C614

[1055] Amount made: 14.0 mg. LCMS m/z 381 [M+H] ⁺ , purity (UV/MS) 97/79.

l-d-G-G-pentyl-8-azabicvclorS^.1]octan-8-vnpropylVlH-indo l-3-yl)ethanone C615

[1056] Amount made: 15.0 mg. LCMS m/z 381 [Mn-H] ⁺ , purity (UV/MS) 95/77.

l-π-fS-rS-phenethyl-8-azabicvclorS^.n octan-8-vnpropylVlH-indol-3-ynethanone C616 [1057] Amount made: 9.8 mg. LCMS m/z 415 [M+H] ⁺ , purity (UV/MS) 99/84.

1 -Cl -D-^-fftetrahydrofuran^-vDmethyQpiperazin- 1 -vDpropyl)- 1 H-indol-3-yl)ethanone C617

[1058] • Amount made: 8.2 mg. LCMS m/z 370 [M+H] ⁺ , purity (UV/MS) 90/57.

1 -f 1 -(3-f4-q H-indol-4-vDpiperazin- 1 -vOpropylV 1 H-indol-3-yl)ethanone C618

[1059] Amount made: 15.7 mg. LCMS m/z 401 [M+H] ⁺ , purity (UV/MS) 82/41.

l -ri-rS^-d-phenylethvπpiperazin-l-vπpropylVlH-indol-3-yl)et hanone C619

[1060] Amount made: 10.7 mg. LCMS m/z 390 [M+H] ⁺ , purity (UV/MS) 93/72.

1 -( 1 -(3-(4-(I -phenylethyDpiperazin- 1 -yDpropylVl H-indol-3-vPpropan- 1 -one C620

[1061] Amount made: 10.9 mg. LCMS m/z 404 [M+H] ⁺ , purity (UV/MS) 100/84.

1 -(l-(3-(4-(2-(diisopropylarnino ^* )ethyl>piperazin-l-yOpropyl>-l H-indol-3-yQethanone C621 [1062] Amount made: 13.2 mg. LCMS m/z 413 [M+H] ⁺ , purity (UV/MS) 95/50.

l -(l-(3-(4-(2-(methylthio)phenvπpiperazin-l-yl)propyl>-lH -indol-3-yl)ethanone C622

[1063] Amount made: 11.3 mg. LCMS m/z 408 [M+H] ⁺ , purity (UV/MS) 84/51.

l-(l-(3-(4-(2,4-difluorobenzoy0piperidin-l-vDpropylVlH-in dol-3-yl)ethanone C623

[1064] Amount made: 4.4 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 72/53.

l-(l-(3-(4-r2-chlorophenoxy)piperidin-l-ylV2-hvdroxypropyl&g t;l H-indol-3-yπethanone C624 ^• [1065] Amount made: 17.4 mg. LCMS m/z 427 [M+H] ⁺ , purity (UV/MS) 100/95.

l-(l-(3-(4-(2-chlorophenoxy)piperidin-l -yπpropyl>-lH-indol-3-ylV2,2,2-trifluoroethanone C625

[1066] Amount made: 10.1 mg. LCMS m/z 465 [M+H] ⁺ , purity (UV/MS) 97/86.

l-(l-(3-(4-(2-chlorophenoxy)piperidin-l-yl)propylVlH-indo l-3-yl)-3-methylbutan-l-one C626

[1067] Amount made: 8.7 mg. LCMS m/z 453 [M+H] ⁺ , purity (UV/MS) 96/80.

1 -(I -(3-(4-(2-chlorophenoxy')piperidin-l -yl)propyl)-lH-indol-3-yDethanone hydrochloride C627

[1068] Amount made: 20.2 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 98/72.

l-(l-r3-(4-(2-chlorophenoxy)piperidin-l-yl)propyl>-lH- indol-3-yl)propan-l-one C628

[1069] Amount made: 5.9 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 100/81.

1 -f 1 -(3-(4-f2-chlorophenoxy ^' )piperidin- 1 -vDpropyl)-4-methoxy- 1 H-indol-3-yl ^" )ethanone C629

[1070] Amount made: 4.6 mg. LCMS m/z 441 [M-I-H] ⁺ , purity (UV/MS) 99/89.

l-π-( ^' 3-f4-(2-chlorophenoxy')piperidin-l-yl ^* )propyl ^' >-5-methoxy-lH-indol-3-yl ^' )ethanone C630

[1071] Amount made: 5.6 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 99/86.

l-(l-(3-r4-(2-chlorophenoxy)piperidin-l-vπpropyl')-5-methox y-lH-indol-3-yl ^' )pentani-l-one C631

[1072] Amount made: 5.5 mg. LCMS m/z 483 [M+H] ⁺ , purity (UV/MS) 96/81.

l-(l-(3-r4-(2-chlorophenoxy)piperidin-l-yl)propylV6-metho xy-lH-indol-3-vπethanone C632

[1073] Amount made: 12.3 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 98/90.

1 -(I -( ^" 3-(4-(2-chIorophenyl)piperazin- 1 -yDpropylV 1 H-indol-3-y Dethanone hydrochloride

C633

[1074] Amount made: 9.1 mg. LCMS m/z 396 [M-HH] ⁺ , purity (UV/MS) 82/58.

l-(l-(3-(4-(2-ethoxyethyl)piperazin-l-vnpropyl)-lH-indol- 3-yl)ethanone C634

[1075] Amount made: 6.3 mg. LCMS m/z 358 [M+H] ⁺ , purity (UV/MS) 88/57.

1 -(I -f3-(4-(2-methoxyethyDpiperazin-l-yl)propyl)-l H-indol-3-vQethanone C636

[1076] Amount made: 9.1 mg. LCMS m/z 344 [M+H] ⁺ , purity (UV/MS) 96/86.

1 -( 1 -(3 -(4-(2-methoxyphenyl)piperidin- 1 -y l)-2-methylpropy IV 1 H-indol-3 -vDethanone C637 [1077] Amount made: 4.8 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 99/75.

1 -(I -(3-(4-(2-methoxyphenyl)piperidin-l -yl)propyl>lH-indol-3-yl)-3-methylbutan-l -one C638

[1078] Amount made: 12.0 mg. LCMS m/z 433 [M+H] ⁺ , purity (UV/MS) 97/72.

l-(l-(3-(4-(2-methoxyphenyl ^' )piperidin-l-yl ^' )propyl ^' )-lH-indol-3-yl)ethanone C639

[1079] Amount made: 4.8 mg. LCMS m/z 391 [M+H] ⁺ , purity (UV/MS) 81/69.

1 -( 1 -(3-(4-(2-methoxyphenvPpiperidin- 1 -yQpropylV 1 H-indol-3-yOpropan- 1 -one C640

11080] Amount made: 10.9 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 97/81.

l -d-π-^-^-chlorophenoxy^piperidin-l-vπ^-hydroxypropylVlH-in dol-3-vDethanone C641 [1081] Amount made: 9.6 mg. LCMS m/z 427 [M+H] ⁺ , purity (UV/MS) 80/58.

l -π-(3-(4-(4-chlorophenoxy ^' )piperidin-l-yl ^' )propyl>lH-indol-3-ylV2,2,2-trifluoroethanone C642

[1082] Amount made: 5.2 mg. LCMS m/z 465 [M+H] ⁺ , purity (UV/MS) 74/75.

l -d -O-^^-chlorophenoxy^piperidin-l-yDpropylVlH-indol-3-vπ-S-me thylbutan-l-one C643

[1083] Amount made: 4.7 mg. LCMS m/z 453 [M+H] ⁺ , purity (UV/MS) 92/65.

1 -( 1 -f 3-(4-(4-chlorophenoxy')piperidin- 1 -yl)propyl)- 1 H-indol-3 -vPethanone C644

[1084] Amount made: 16.6 mg. LCMS m/z 411 [M+H] ⁺ , purity (UV/MS) 96/71.

1 -(I -f3-(4-(4-chlorophenoxy)piperidin- 1 -yPpropylM-methoxy-l H-indol-3-yl')ethanone C645

[1085] Amount made: 2.3 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 92/51.

1 -( 1 -(3 -(4-(4-chlorophenoxy)piperidin- 1 -y Dpropy 1V5 -methoxy- 1 H-indol-3 -y Dethanone C646

[1086] Amount made: 3.0 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 92/57.

l-(l-(3-r4-(4-chlorophenoxy ^* )piperidin-l-yπpropyl>-5-methoxy-lH-indol-3-yl')pentan-l -one C647

[1087] Amount made: 3.5 mg. LCMS m/z 483 [M+H] ⁺ , purity (UV/MS) 84/47.

1 -( 1 -(3-f 4-(4-chlorophenoxy ^* )piperidin- 1 -vOpropylV 6-methoxy- 1 H-indol-3 -vPethanone C648

[1088] Amount made: 4.8 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 85/58.

1 -( 1 -f 3-f 4-f4-chlorophenylsulfonyl')piperidin- 1 -vDpropyl)- 1 H-indol-3-vIV2.2.2- trifluoroethanone C649

[1089] Amount made: 5.6 mg. LCMS m/z 513 [M+H] ⁺ , purity (UV/MS) 100/70.

l-(l-(3-(4-(4-chlorophenylsulfonyl ^' )piperidin-l-yπpropyl)-lH-indol-3-yl ^' )ethanone hydrochloride C650

[1090] Amount made: 21.0 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 97/62.

l-n-n-(4-(4-chlorophenylsulfonyl)piperidin-l-vnpropyl)-lH-in dol-3-yl)propan-l-one C651 [1091] Amount made: 10.6 mg. LCMS m/z 473 [M+H] ⁺ , purity (UV/MS) 100/80.

l-d-f3-r4-r4-chlorophenylthio)piperidin-l-yl)propyl)-lH-i ndol-3-yl)ethanone hydrochloride C652

[1092] Amount made: 14.4 mg. LCMS m/z 427 [M+H] ⁺ , purity (UV/MS) 98/72.

1 -(I -(3-f4-C4-fluorophenoxy)piperidin-l -yl)-2-hydroxypropyl>- 1 H-indol-3 -vDethanone C653 [1093] Amount made: 9.6 mg. LCMS m/z 41 1 [M+H] ⁺ , purity (UV/MS) 100/87.

l-ri-(3-(4-(4-fluorophenoxy)piperidin-l-yl)-2-methylpropyl ^* )-lH-indol-3-yπethanone C654 [1094] Amount made: 1.1 mg. LCMS m/z 409 [M+H] ⁺ , purity (UV/MS) 100/78.

l-(l-(3-(4-(4-fluorophenoxy)piperidin-l-yl)propylVlH-indol-3 -yl ^' )-3-methylbutan-l-one C655

[1095] Amount made: 10.2 mg. LCMS m/z 437 [M+H] ⁺ , purity (UV/MS) 98/80.

l-(l-C3-f4-(4-fluorophenoxy)piperidin-l-yl)propyiyi H-indol-3 -yPethanone hydrochloride C656

[1096] Amount made: 9.0 mg. LCMS m/z 395 [M+H] ⁺ , purity (UV/MS) 88/76.

1 -Cl -( 3-(4-(4-fluorophenoxy ^' )piperidin- 1 -yDpropylV 1 H-indol-3-vOpropan- 1 -one C657

[1097] Amount made: 9.8 mg. LCMS m/z 409 [M+H] ⁺ , purity (UV/MS) 99/80.

1 -(I -(3-(4-(4-fluorophenoxy )piperidin-l-vπpropylV4-methoxy-lH-indol-3-yl)ethanone C658

[1098] Amount made: 4.5 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 98/86.

l-(l-(3-( ^' 4-(4-fluorophenoxy')piperidin-l-vπpropyl ^' )-5-methoxy-lH-indol-3-yl')ethanone C659

[1099] Amount made: 5.2 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 100/89.

1 -(I -(3-(4-(4-fluorophenoxy)piperidin- 1 -yQpropyI)-5-methoxy- 1 H-indol-3-yl ^" )pentan- 1 -one C660

[1100] Amount made: 5.5 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 98/80.

1 -( 1 -(3 -(4-(4-fl uorophenoxy)piperidin- 1 -vOpropyl V 6-methoxy- 1 H-indol-3 -vPethanone C661

[1101] Amount made: 10.7 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 100/96.

1 -(I -(3-(4-(allyloxy)piperidin-l-yl ^' )propylVlH-indol-3-yl ^' )ethanone C662

[1102] Amount made: 9.0 mg. LCMS m/z 341 [M+H] ⁺ , purity (UV/MS) 99/70.

1 -( 1 -(3-(4-(benzo[ ^' d ^' )thiazol-2-yPpiperidin- 1 -yP-2-hy droxypropylV 1 H-indol-3-yPethanone C663

[1103] Amount made: 5.6 mg. LCMS m/z 434 [M+H] ⁺ , purity (UV/MS) 97/79.

1 -(I -(3-(4-(benzo( ^" d ^" |thiazol-2-yπpiperidin-l -yl>2~methylpropyl)-lH-indol-3-yDethanone C664

[1104] Amount made: 1.0 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 91/58.

l-(l-(3-(4-(benzord1thiazol-2-ynpiperidin-l-ynpropylVlH-i ndol-3-ylV2.2.2- trifluoroethanone C665

[1105] Amount made: 8.4 mg. LCMS m/z 472 [M+H] ⁺ , purity (UV/MS) 100/98.

l-d-(3-( ^' 4-rbenzo| ^' d ^' |thiazol-2-yl ^> )piperidin-l-vπpropylVlH-indol-3-ylV3-niethylbυtan-l-one C666

[1106] Amount made: 10.4 mg. LCMS m/z 460 [M+H] ⁺ , purity (UV/MS) 100/94.

l-(l-Q-(4-(benzo[d]thiazol-2-yl)piperidin-l-vπpropyl)-lH -indol-3-vπethanone C667

[1107] Amount made: 20.7 mg. LCMS m/z 418 [M+H] ⁺ , purity (UV/MS) 99/68.

l-π-O-^-rbenzofdlthiazol^-vDpiperidin-l-yπpropylVlH-indol- 3-yπpropan-l-one C668 [1108] Amount made: 9.4 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 97/82.

l-(l-(3-r4-(benzo[d1thiazol-2-yl')piperidin-l-vπpropyl&g t;-4-methoxy-lH-indol-3-yπethanone C669

[1109] Amount made: 1.7 mg. LCMS m/z 448 [M+H] ⁺ , purity (UV/MS) 93/72.

l-(l-r3-(4-(benzo[ ^' dlthia2ol-2-yl ^' )piperidin-l-yl)propyl ^' )-6-methoxy-lH-indol-3-vπethanone C670

[1110] Amount made: 1 1.0 mg. LCMS m/z 448 [M+H] ⁺ , purity (UV/MS) 99/86.

l-d-(3-(4-(cvclopropylmethoxy)piperidin-l-yl)propyl)-lH-i ndol-3-yl>ethanone C671

[1111] Amount made: 9.3 mg. LCMS m/z 355 [M+H] ⁺ , purity (UV/MS) 97/81.

1 -( 1 -f 3-(4-(methoxymethy Dpiperidin- 1 -yPpropyl)- 1 H-indol-3 -vPethanone C672

{1112] Amount made: 14.2 mg. LCMS m/z 329 [M+H] ⁺ , purity (UV/MS) 100/87.

1 -( 1 -f 3-(4-(pyrrolidin- 1 -y Dpiperidin- 1 -vDpropylV 1 H-indol-3 -y Dethanone C673

[1113] Amount made: 7.1 mg. LCMS m/z 354 [M+H] ⁺ , purity (UV/MS) 96/83.

l-(l-(3-r4-benzoylpiperidin-l-yπ-2-hydroxypropylVlH-indol-3 -yl ^' )ethanone C674

[1114] Amount made: 14.3 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 99/95.

l-(l-(3-(4-benzoylpiperidin-l -vD-2-methylpropylVl H-indol-3 -vDethanone C675

[1115] Amount made: 1.9 mg. LCMS m/z 403 [M+H] ⁺ , purity (UV/MS) 96/65.

l-π-(3-(4-benzoylpiperidin-l-yl)propyiyiH-indol-3-yl)-2, 2,2-trifluoroethanone C676

[1116] Amount made: 8.5 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 100/97.

l-π-r3-r4-benzoylpiperidin-l-yl)propylVlH-indol-3-yl)-3- methylbutan-l-one C677

[1117] Amount made: 11.3 mg. LCMS m/z 431 [M+H] ⁺ , purity (UV/MS) 100/89.

1 -( 1 -( 3 -(4-benzoy Ipiperidin- 1 -y DpropylV 1 H-indol-3 -vPpropan- 1 -one C678

[1118] Amount made: 7.2 mg. LCMS m/z 403 [M-I-H] ⁺ , purity (UV/MS) 99/83.

l -(l-f3-r4-benzoylpiperidin-l -vπpropyl)-4-methoxy-lH-indol-3-vπethanone C679

[1119] Amount made: 4.3 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 94/75.

1 -d -(3 -f 4-benzoylpiperidin- 1 -y 0propyiy5-bromo- 1 H-indol-3-yDethanone C680

[1120] Amount made: 6.4 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 98/76.

l-n-(3-(4-benzoylpiperidin-l-yl)propyiyS-methoxy-lH-indol -3-yl)ethanone C681

[1121] Amount made: 2.7 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 98/64.

l-π-(3-(4-benzoylpiperidin-lλ4)propyl>5-methoxy-lH-i ndol-3-yl)pentan-l-one C682

[1122] Amount made: 5.1 mg. LCMS m/z 461 [M+H] ⁺ , purity (UV/MS) 99/81.

1 -(I -(3-(4-benzoylpiperidin-l -yl)propyl>6-bromo-lH-indol-3-vDethanone C683

[1123] Amount made: 7.8 mg. LCMS m/z 467 [M+H] ⁺ , purity (UV/MS) 99/85.

1 -(I -(3-(4-benzoylpiperidin- 1 -yl)propyl>6-methoxy- 1 H-indol-3-yl)ethanone C684

[1124] Amount made: 11.7 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 99/87.

l-(l-r3-(4-benzyl-4-hvdroxypiperidin-l-yl)-2-methylpropyl ^' )-lH-indol-3-vπethanone C685 [1125] Amount made: 2.5 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-(4-benzyl-4-hvdroxypiperidin-l-vπpropyl>-lH-i ndol-3-yl)-2,2,2-trifluoroethanone C686

[1126] Amount made: 1.2 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(l-(3-(4-benzyl-4-hvdroxypiperidin-l-yl')propyl>-lH- indol-3-vπpropan-l-one C687

[1127] Amount made: 5.2 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 99/90.

l -π-C3-(4-benzylpiperidin-l-yl')-2-methylproDylVlH-indol-3-y l)ethanone C688

[1128] Amount made: 3.2 mg. LCMS m/z 389 [M+H] ⁺ ₅ purity (UV/MS) 98/80.

l -(l-C3-( ^' 4-ben2υlpiperidin-l-yl'>propyl'>-lH-indol-3-vn-2.2.2- trifluoroethanone C689

[1129] Amount made: 2.4 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -(I -(3-(4-benzylpiperidin-l -vDpropylV lH-indol-3-vDethanone C690

[1130] Amount made: 12.6 mg. LCMS m/z 375 [M+H]\ purity (UV/MS) 99/93.

1 -(I -(3-(4-benzylpiperidin-l -vDpropyD-l H-indol-3-vDpropan- 1 -one C691

[1131] Amount made: 6.0 mg. LCMS m/z 389 [M-FH] ⁺ , purity (UV/MS) 100/100.

l-(l-(3-(4-butylpiperidin-l-ylV2-methvbropylVlH-indol-3-y l)ethanone C692

[1132] Amount made: 4.6 mg. LCMS m/z 355 [M+H] ⁺ , purity (UV/MS) 100/81.

1 -(I -f 3-f4-butylpiperidin- 1 -yDpropylV 1 H-indol-3-ylV2,2.2-trifluoroethanone C693

[1133] Amount made: 7.2 mg. LCMS m/z 395 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(l-(3-(4-butylpiperidin-l -vnpropylVlH-indol-3-vn-3-methylbutan-l-one C694

[1134] Amount made: 9.8 mg. LCMS m/z 383 [M+H] ⁺ , purity (UV/MS) 99/95.

l-(l-(3-(4-butylpiperidin-l -yl)propylMH-indol-3-yDpropan-l-one C695

[1135] Amount made: 11.1 mg. LCMS m/z 355 [M+H] ⁺ , purity (UV/MS) 100/96.

1 -(I -(3 -(4-buty lpiperidin- 1 -yl)propyl>4-methoxy- 1 H-indol-3-y Dethanone C696

[1136] Amount made: 4.6 mg. LCMS m/z 371 [M+H] ⁺ , purity (UV/MS) 100/94.

l-π-(3-(4-butyIpiperidin-l-yl)propyl>5-methoxy-lH-ind ol-3-yl)ethanone C697

[1137] Amount made: 5.2 mg. LCMS m/z 371 [M+H] ⁺ , purity (UV/MS) 100/96.

1 -( 1 -(3-(4-butylpiperidin- 1 -vDpropyl>5-methoxy- 1 H-indol-3-yl ^* )pentan- 1 -one C698

[1138] Amount made: 4.7 mg. LCMS m/z 413 [M+H] ⁺ , purity (UV/MS) 100/95.

l-(l-(3-(4-butylpiperidin-l-vπpropyl ^' )-6-methoxy-lH-indol-3-yπethanone C699

[1139] Amount made: 9.1 mg. LCMS m/z 371 [M+H] ⁺ , purity (UV/MS) 100/98.

1 -( 1 -( ^" 3-r4-hexylidenepiperidin- 1 -vDpropyl V 1 H-indol-3-yPethanone C70Q

[1140] Amount made: 8.2 mg. LCMS m/z 367 [M+H] ⁺ , purity (UV/MS) 79/78.

1 -( 1 -(3 -(4-hexylpiperidin- 1 -y PpropylV 1 H-indo 1-3 -vDethanone C701

[1141] Amount made: 7.7 mg. LCMS m/z 369 [M+H] ⁺ , purity (UV/MS) 89/80.

1 -( 1 -(3-(4-isopentylpiperidin- 1 -yPpropylV 1 H-indol-3 -yDethanone C702

[1142] Amount made: 3.0 mg. LCMS m/z 355 [M+H] ⁺ , purity (UV/MS) 87/90.

1-(1 -(3-(4-pentylidenepiperidin-l-y0propyiyi H-indol-3-yl)ethanone C703

[1143] Amount made: 17.5 mg. LCMS m/z 353 [MH-H] ⁺ , purity (UV/MS) 94/74.

1-Cl -(3-(4-phenylpiperazin- 1 -vOpropyl)- 1 H-indol-3 -vPethanone C704

[1144] Amount made: 10.7 mg. LCMS m/z 362 [M-t-H] ⁺ , purity (UV/MS) 93/55.

l-(l-(3-(4-phenylpiperidin-l-yPpropyiyiH-indol-3-yPethano ne C705

[1145] Amount made: 12.0 mg. LCMS m/z 361 [M+H] ⁺ , purity (UV/MS) 96/68.

1-(1 -fS-^-propoxypiperidin-l-yπpropyP-l H-indol-3-vDethanone C706

[1146] Amount made: 10.4 mg. LCMS m/z 343 [M+H] ⁺ , purity (UV/MS) 99/91.

l-(l-(3-(4-propylpiperazin-l-yl)propyl>lH-indoI-3-yl)e thanone C707

[1147] Amount made: 9.4 mg. LCMS m/z 328 [M+H] ⁺ , purity (UV/MS) 78/65.

l -(l -(3-(5-butyl-2.5-diazabicvclor2.2.11heptan-2-ynpropyiyiH-ind ol-3-yl)ethanone C708 [1148] Amount made: 3.6 mg. LCMS m/z 354 [M+H] ⁺ , purity (UV/MS) 88/67.

l-fl -(3-r6-methoxy-3,4-dihvdro-lH-pyridor3.4-b1indol-2f9H)-vnDro pylVlH-indol-3-vn-3- methylbutan-1-one C709

[1149] Amount made: 5.5 mg. LCMS m/z 444 [M+H] ⁺ , purity (UV/MS) 88/47.

1 -(I -(3-fmethviα-fpyridin-σ-vnethvnamino^propylVlH-indol-3-yl) ethanone C710

[1150] Amount made: 10.4 mg. LCMS m/z 336 [M+H] ⁺ , purity (UV/MS) 85/55.

l -d-O-Coctahvdroisoquinolin^dHO-vπpropylVlH-indol-3-vDethano ne C711

[1151] Amount made: 23.5 mg. LCMS m/z 339 [M+H] ⁺ , purity (UV/MS) 100/74.

1 -( 1 -(3 -(piperidin- 1 -y QpropylV 1 H-indol-3 -vDethanone C712

[1152] Amount made: 14.3 mg. LCMS m/z 285 [M+H] ⁺ , purity (UV/MS) 100/77.

l-(l-(3-moφholinopropyl ^* )-lH-indol-3-yl)ethanone C713

[1153] Amount made: 9.4 mg. LCMS m/z 287 [M+H] ⁺ , purity (UV/MS) 99/77.

1 -(I -(4-(3-(4-chlorophenoxy)-8-azabicyclor3.2.1 loctan-8-yl)butyl>- 1 H-indol-3-yl)ethanone C714

[1154] Amount made: 3.4 mg. LCMS m/z 451 [M+H] ⁺ , purity (UV/MS) 68/40.

l-ri^-G^-fluorophenyn^-hydroxy-8-azabicyclorS^.ηoctan-S- ynbutylVlH-indol-3- yQethanone C715

[1155] Amount made: 2.8 mg. LCMS m/z 435 [M-I-H] ⁺ , purity (UV/MS) 98/80.

l-π^-fS^cyclopropylmethoxyVδ-azabicvclorS^.ηoctan-S-vn butylVlH-indol-3- vOethanone C716

[1156] Amount made: 7.0 mg. LCMS m/z 395 [M+H] ⁺ , purity (UV/MS) 100/80.

l-( l-(4-(4-(l -phenylethyHpiperazin-l -vObutylVl H-indol-3-yl)ethanone C717

[1157] Amount made: 11.1 mg. LCMS m/z 404 [M+H] ⁺ , purity (UV/MS) 98/65.

l-(l-(4-(4-(2-chlorophenoxy)piperidin-l-vπbutylVlH-indol -3-yl)ethanone C718

[1158] Amount made: 11.5 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 100/84.

1 -(I -(4-(4-(2-methoxyphenvDpiperidin- 1 -vDbutylV 1 H-indol-3-vπethanone C719

[1159] Amount made: 13.8 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 100/98.

1 -( 1 -(4-f 4-(4-fluorophenoxy)piperidin- 1 -vHbutyl V 1 H-indol-3 -v Dethanone C720

[1160] Amount made: 11.9 mg. LCMS m/z 409 [M+H] ⁺ , purity (UV/MS) 100/87.

1 -( 1 -(4-(4-fbenzo rdlthiazol -2-vnpiperidin- 1 -vHbutyl V 1 H-indol-3 -yltethanone C721

[1161] Amount made: 11.8 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 98/63.

l-π-f4-(4-benzoylpiperidin-l-vnbutylVlH-indol-3-yl)ethan one C722

[1162] Amount made: 14.4 mg. LCMS m/z 403 [M+H] ⁺ , purity (UV/MS) 98/84.

1 -(I -(4-(4-benzyl-4-hvdroxypiperidin- 1 -vDbutylV 1 H-indol-3-vπethanone C723

[1163] Amount made: 3.4 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 99/90.

l-(l-(4-(4-benzylpiρeridin-l-yl)butγlHH-indol-3-yDethan one C724

[1164] Amount made: 6.0 mg. LCMS m/z 389 [M+H] ⁺ , purity (UV/MS) 99/90.

1 -( 1 -(4-( 4-butylpjperidin- 1 -vObutylV 1 H-indol-3-y Dethanone C725

[1165] Amount made: 13.8 mg. LCMS m/z 355 [M+H] ⁺ , purity (UV/MS) 100/88.

l-d^-fά-methoxy-S^-dihvdro-lH-pyridorS^-blindol-σ^HVvnb utylVlH-indol^- vHethanone C726

[1166] Amount made: 3.5 mg. LCMS m/z 416 [M+H] ⁺ , purity (UV/MS) 92/53.

^^-(S-acetyl-lH-indol-l-vπpropyD-N.N-diethylpiperidine-S -carboxamide C727

[1167] Amount made: 11.7 mg. LCMS m/z 384 [M+H] ⁺ , purity (UV/MS) 100/86.

1 -(4-methoxy- 1 -(3 -(4-( 1 -phenylethyDpiperazin-1 -vDpropylV 1 H-indol-3-vDethanone C728 [1168] Amount made: 9.5 mg. LCMS m/z 420 [M+H] ⁺ , purity (UV/MS) 94/66.

l-(4-methoxy-l-r3-C4-( ^" 2-methoxyphenyl ^> )piperidin-l-yl)propyl>lH-indol-3-vπethanone C729

(11691 Amount made: 8.3 mg. LCMS m/z 421 [M+H] ⁺ , purity (UV/MS) 99/82.

l-(4-methoxy-l-(3-(4-propoxypiperidin-l-yDpropylVlH-indol -3-yl)ethanone C730

[1170] Amount made: 1.6 mg. LCMS m/z 373 [M+H] ⁺ , purity (UV/MS) 66/66.

1 -(4-methoχy- 1 -(3 -(6-methoxy-3.4-dihvdro- 1 H-pyridor3.4-b1indol-2(9HVyr)propy IV 1 H- indol-3-yl)ethanone C731

[1171] Amount made: 1.9 mg. LCMS m/z 432 [M+H] ⁺ ₅ purity (UV/MS) 86/42.

l-(5-bromo-l-(3-(3-rcyclopropylmethoxyV8-azabicvclo[3.2.1]oc tan-8-yl ^' )propylVlH-indol-3- vPethanone C732

[1172] Amount made: 6.9 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 98/82.

1 -(5-bromo-l -(3-(4-Cl -phenylethvDpiperazin- 1 -vDpropylV 1 H-indol-3-vπethanone C733 [1173] Amount made: 9.8 mg. LCMS m/z 468 [M+H] ⁺ , purity (UV/MS) 99/66.

1 -( 5-bromo- 1 -(3-(4-(2-chlorophenoxy)piperidin- 1 -yPpropylV 1 H-indol-3 -vDethanone C734 [1174] Amount made: 5.4 mg. LCMS m/z 489 [M+H] ⁺ , purity (UV/MS) 99/84.

1 -(5-bromo- l-(3-f4-(4-fluorophenoxy')piperidin-l-yl ^' )propy IV lH-indol-3-vPethanone C735 [1175] Amount made: 6.7 mg. LCMS m/z 473 [M+H] ⁺ , purity (UV/MS) 97/90.

1 -(5-bromo-l -(3-(4-propoxypiperidin-l-yOpropyiyiH-indol-3-yQethanone C736

[1176] Amount made: 1.7 mg. LCMS m/z 421 [M+H] ⁺ , purity (UV/MS) 83/71.

1 -(5-methoxy- 1 -O -(4-(I -phenylethyDpiperazin- 1 -vDpropylV 1 H-indol-3 -vDethanone C737 [1177] Amount made: 8.9 mg. LCMS m/z 420 [M+H] ⁺ , purity (UV/MS) 98/64.

l-(5-methoxy-l-(3-(4-(l-phenylethyπpiperazin-l-vπpropyl VlH-indol-3-yl)pentan-l -one C738

[1178] Amount made: 8.6 mg. LCMS m/z 462 [M+H] ⁺ , purity (UV/MS) 98/86.

1 -(5-methoxy- 1 -(3-(4-(2-methoxyphenvQρiperidin- 1 -vDpropylVl H-indol-3-yl)ethanone C739

[1179] Amount made: 8.1 mg. LCMS m/z 421 [M+H] ⁺ , purity (UV/MS) 99/82.

l-r5-methoxy-l-(3-(4-(2-methoxyphenyl ^' )piperidin-l -yl)propylVlH-indol-3-yl)pentan-l-one C740

[1180] Amount made: 7.7 mg. LCMS m/z 463 [M+H] ⁺ , purity (UV/MS) 97/74.

1 -(5-methoxy- l-(3-(4^ropoxypiperidin-l-yI)propyl)-lH-indol-3-vDpentan-l -one C741

[1181] Amount made: 1.8 mg. LCMS m/z 415 [M+H] ⁺ , purity (UV/MS) 85/70.

1 -f 5 -methoxy- 1 -(3-(6-methoxy-3 ,4-dihydro- 1 H-pyrido f3 ,4-blindol -2(9HVv Hpropyl V 1 H- indol-3 -y Dpentan- 1 -one C742

[1182] Amount made: 3.2 mg. LCMS m/z 474 [M+H] ⁺ , purity (UV/MS) 81/25.

l-(6-bromo-l-(3-(3-(4-chlorophenoxyV8-azabicvclor3.2.noct an-8-yl)propyl)-lH-indol-3- vQethanone C743

[1183] Amount made: 1.1 mg. LCMS m/z 515 [M+H] ⁺ , purity (UV/MS) 100/55.

l-r6-bromo-l-(3-(3-(cvclopropylmethoxyV8-azabicyclo[3.2.1 ]octan-8-vπpropylVlH-indol-3- vDethanone C744

[1184] Amount made: 8.2 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 96/70.

l -r6-bromo-l-(3-r4-π-phenylethyl ^' )piperazin-l -yl)propyl>-lH-indol-3-yπethanone C745

[1185] Amount made: 9.0 mg. LCMS m/z 468 purity (UV/MS) 100/64.

l -(6-bromo-l-(3-f4-(2-chlorophenoxy)piperidin-l-yl)propylVlH- indol-3-yl ^' )ethanone C746 [1186] Amount made: 8.8 mg. LCMS m/z 489 [M+H] ⁺ , purity (UV/MS) 97/84.

1 -f6-bromo- 1 -(3-f4-f4-chlorophenoxy ^' )piperidin-l -vDpropylVl H-indol-3-yDethanone C747 [1187] Amount made: 2.3 mg. LCMS m/z 489 [M+H] ⁺ , purity (UV/MS) 100/75.

I -(6-bromo- 1 -(3-(4-(4-fluorophenoxy)piperidin- 1 -yQpropyl)- 1 H-indσl-S-vDethanone C748 [1188] Amount made: 5.0 mg. LCMS m/z 473 [M+H] ⁺ , purity (UV/MS) 95/68.

l-(6-bromo-l-(3-(4-bu1ylpiperidin-l-yl)propyl>lH-indol -3~yl)ethanone C749

[1189] Amount made: 4.1 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -f 6-bromo- 1 -(3-(4-propoxypiperidin-l -vDpropyD- 1 H-indol-3-yl ^* )ethanone C75Q

[1190] Amount made: 3.2 mg. LCMS m/z 421 [M+H] ⁺ , purity (UV/MS) 100/63.

1 -(6-methoxy- 1 -( ^" 3 -(4-( 1 -phenylethvPpiperazin- 1 -vDpropyl> 1 H-indol-3 -y Dethanone C751 [1191] Amount made: 16.1 mg. LCMS m/z 420 [M+H] ⁺ , purity (UV/MS) 100/91.

1 -(6-methoxy- 1 -(3-(4-(2-methoxyphenyl)piperidin- 1 -vDpropylV 1 H-indol-3-yPethanone C752

[1192] Amount made: 15.7 mg. LCMS m/z 421 [M+H] ⁺ , purity (UV/MS) 99/90.

1 -(6-methoxy- l-(3-(4-propoxypiperidin-l-v0propyiyiH-indol-3-yl)ethanone C753

[1193] Amount made: 3.0 mg. LCMS m/z 373 [M+H] ⁺ , purity (UV/MS) 80/68.

l-(6-methoxy-l-(3-(6-methoxy-3,4-dihvdro-lH-pyridor3,4-blind ol-2(9HVyl ^' )propylVlH- indol-3-yl)ethanone C754

[1194] Amount made: 5.9 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 90/61.

2-(4-(3-(3-acetyl-lH-indol-l-yl)propyQpiperazin-l-ylVl-mo φholinoethanone C755

[1195] Amount made: 10.2 mg. LCMS m/z 413 [M+H] ⁺ , purity (UV/MS) 93/70.

2-(4-(3-(3-acetyl-lH-indol-l-v0propyl)piperazin-l-yl)-N,N -dimethylacetamide C756

[1196] Amount made: 12.2 mg. LCMS m/z 371 [M-I-H] ⁺ , purity (UV/MS) 93/61.

σ^^-trifluoro-l-d^-P^-fluorophenyπ-S-hydroxy-S-azabicvc lorS^.lioctan-S-yπpropylV lH-indol-3-yl)ethanone C757

[1197] Amount made: 9.4 mg. LCMS m/z 475 [M+H] ⁺ , purity (UV/MS) 99/80.

2,2,2-trifluoro-l -π-( ^' 3-(4-(l-phenylethyl)piperazin-l-yl)propyl>lH-indol-3-vπe thanone C758

{1198] Amount made: 9.3 mg. LCMS m/z 444 [M+H] ⁺ , purity (UV/MS) 99/75.

2,2,2-trifluoro-l -(I -(3-(4-(2-methoxyphenvPpiperidin-l -yI)propylHH-indol-3-vQethanone C759

[1199] Amount made: 10.9 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 99/84.

2,2.2-trifluoro- 1 -f 1 -(3-(4-(4-fluorophenoxy)piperidin- 1 -vπpropyD-1 H-indol-3-yDethanone C760

[1200] Amount made: 9.4 mg. LCMS m/z 449 [M+H] ⁺ , purity (UV/MS) 99/97.

2,2,2-trifluoro-l-fl-r3-('4-propoxypiperidin-l-yπpropylV lH-indol-3-yπethanone C761

[1201] Amount made: 3.0 mg. LCMS m/z 397 [M+H] ⁺ , purity (UV/MS) 97/85.

2,2,2-trifluoro-l-fl-r3-(6-methoxy-3.4-dihvdro-lH-pyridor 3,4-b1indol-2<'9H)-ynpropylVlH- indol-3-y0ethanone C762

[1202] Amount made: 3.0 mg. LCMS m/z 456 [M+H] ⁺ , purity (UV/MS) 87/44.

S-methyl-l-d-π-^-d-phenylethyDpiperazin-l-vDpropyD-lH-indol ^-yDbutan-l-one C763 [1203] Amount made: 13.3 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 99/91.

3-methyl- 1 -(I -(3-(4-propoxypiperidin- l-vPpropyl)- 1 H-indol-3-vQbutan- 1 -one C764

[1204] Amount made: 2.3 mg. LCMS m/z 385 [M+H] ⁺ , purity (UV/MS) 97/79.

4-(4-(3-(3-acetyl- 1 H-indol- 1 -yPpropyDpiperazin-l -yPbenzonitrile hydrochloride C765

[1205] Amount made: 3.7 mg. LCMS m/z 387 [M+H] ⁺ , purity (UV/MS) 84/41.

ethyl l-(2-(3 -acetyl- 1 H-indol- 1 -vOethyDpiperidine-4-carboxylate C766

[1206] Amount made: 0.8 mg. LCMS m/z 343 [M+H] ⁺ , purity (UV/MS) 100/100.

ethyl l-(3-(3-(2,2,2-trifluoroacetyiy 1 H-indol- l-vPpropyPpiperidine-4-carboxyIate C767 [1207] Amount made: 5.1 mg. LCMS m/z 411 [M+H] ⁺ , purity (UV/MS) 93/90.

ethyl l-( ^" 3-(3-propionyl-lH-indol-l-yl)propγl)piperidin&-4-carbox ylate C768

[1208] Amount made: 1.7 mg. LCMS m/z 371 [M+H] ⁺ , purity (UV/MS) 92/90.

N-π-D-rS-acetyl-lH-indol-l-vnpropynpyrrolidin-S-vnacetam ide C769

[1209] Amount made: 12.4 mg. LCMS m/z 328 [M+H] ⁺ , purity (UV/MS) 98/80.

4-(l-(3-r3-("cvclopropylmethoxyV8-a2abicvclo[3.2.1]octan-8-v πpropyl>-lH-indol-3-yl ^* )butan- 2-one C77Q

[1210] Amount made: 5.1 mg. LCMS m/z 409 [M+H] ⁺ , purity (UV/MS) 96/49.

4-( 1 -f 3-(4-(l -phenylethyHpiperazin-l -vDpropylV 1 H-indol-3-vπbutan-2-one C771

[1211] Amount made: 7.8 mg. LCMS m/z 418 [M+H] ⁺ , purity (UV/MS) 95/65.

4-(l-f3-( ^" 4-f2-chlorophenoxy ^" )piperidin-l-yl)propylVlH-indol-3-vnbutan-2-one C772

[1212] Amount made: 9.1 mg. LCMS m/z 439 [M+H] ⁺ , purity (UV/MS) 86/50.

4-(l -(3-(4-f2-methoxyphenyl ^' )pipeπdin-l -yHpropylVl H-indol-3-vnbutan-2-one C773

[1213] Amount made: 10.3 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 80/54.

4-(l-(3-(4-(4-fluorophenoxy')piperidin-l-yl ^' )propyl)-lH-indol-3-yl)butan-2-one C774

[1214] Amount made: 1 1.0 mg. LCMS m/z 423 [M+H] ⁺ , purity (UV/MS) 87/56.

4-fl-f3-(4-(benzo[d1thiazol-2-ynpiperidin-l-yl ^' )propylVlH-indol-3-vnbutan-2-one C775 [1215] Amount made: 9.1 mg. LCMS m/z 446 [M+H] ⁺ , purity (UV/MS) 88/44.

4-( 1 -(3-r4-benzoylpiperidin- 1 -yOpropylV 1 H-indoI-3-yPbutan-2-one C776

[1216] Amount made: 10.2 mg. LCMS m/z 417 [M+H] ⁺ , purity (UV/MS) 92/58.

4-f 1 -(3-f 4-butylpiperidin- 1 -vnpropyl V 1 H-indol-3-vnbutan-2-one C777

[1217] Amount made: 10.2 mg. LCMS m/z 369 [M+H] ⁺ , purity (UV/MS) 83/55.

4-d -(3-(4-propoxypiperidin- 1 -yPpropylV 1 H-indoI-3-yπbutan-2-one C778

[1218] Amount made: 2.7 mg. LCMS m/z 37] [M+H] ⁺ , purity (UV/MS) 70/39.

methyl !-(3-('f2-πH-indol-3-vnethvn( ^" methvnamino')propyl ^' )-l H-indole-3-carboxylate C779 [1219] Amount made: 17.7 mg. LCMS m/z 390 [M+H] ⁺ , purity (UV/MS) 83/52.

methyl l-(3-(2-phenylpropylamino')propyl> lH-indole-3-carboxylate C780

[1220] Amount made: 8.2 mg. LCMS m/z 351 [M+H] ⁺ , purity (UV/MS) 88/80.

methyl l-(3-(3.4-dihvdroisoquinolin-2flH>yl)propyl>lH-indole- 3-carboxylate C781

[1221] Amount made: 12.8 mg. LCMS m/z 349 [M+H] ⁺ , purity (UV/MS) 93/69.

methyl l-(3-(3-acetarnidopyπOlidin-l-vOpropyD-l H-indole-3-carboxylate C782

[1222] Amount made: 12.2 mg. LCMS m/z 344 [M+H] ⁺ , purity (UV/MS) 99/93.

methyl 1 -(3-(4-((tetrahvdrofuran-2-yPmethyl)piperazin- 1 -vDpropylV 1 H-indole-3-carboxylate C783

[1223] Amount made: 14.2 mg. LCMS m/z 386 [M-I-H] ⁺ , purity (UV/MS) 97/78.

methyl 1 -(3-(4-(lH-indol-4-yl)piperazin-l -vPpropyD-l H-indole-3-carboxylate C784

[12241 Amount made: 20.9 mg. LCMS m/z 417 [M+H] ⁺ , purity (UV/MS) 77/43.

methyl l-(3-(4-π-phenylethyl)piperazin-l-vDpropylVl H-indole-3-carboxylate C785

[1225] Amount made: 14.5 mg. LCMS m/z 406 [M+H] ⁺ , purity (UV/MS) 97/93.

methyl 1 -f 3-f 4-(2-(diisopropylamino)ethy Dpiperazin- 1 -yPpropylV 1 H-indole-3-carboxylate C786

[1226] Amount made: 17.7 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 95/65.

methyl l-(3-(4-r2-rdimethylaminoV2-oxoethyl)piperazin-l-vπpropyl&g t;-lH-indole-3- carboxylate C787

[1227] Amount made: 18.7 mg. LCMS m/z 387 [M+H] ⁺ , purity (UV/MS) 97/73.

methyl l-π-r4-r2-(dimethylamino ^> )ethyπpiperazin-l-yl>propylVlH-indole-3-carboxylate

C788

[1228] Amount made: 10.1 mg. LCMS m/z 373 [M+H] ⁺ , purity (UV/MS) 81/41.

methyl 1 -(3 -f 4-(2-(methy lthio)phenyQpiperazin- 1 -yPpropyl)-! H-indole-3-carboxylate C789 [1229] Amount made: 20.1 mg. LCMS m/z 424 [MH-H] ⁺ , purity (UV/MS) 85/57.

methyl 1 -f3-(4-C2.4-difluorobenzoyOpiperidin-l -vDpropylV 1 H-indole-3-carboxylate C790 [1230] Amount made: 21.1 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 80/64.

methyl l -(3-(4-(2-chlorophenyl)piperazin-l-yl>propyiyi H-indole-3-carboxylate hydrochloride C791

[1231] Amount made: 16.7 mg. LCMS m/z 412 [M+H] ⁺ , purity (UV/MS) 88/54.

methyl l-f3-(4-(2-ethoxyethyl)piperazin-l-yl)propyl)-l H-indole-3-carboxylate C792

[1232] Amount made: 15.7 mg. LCMS m/z 374 [M+H] ⁺ , purity (UV/MS) 95/70.

methyl 1 -(3-f4-(2-hydroxyphenyl)piperazin- 1 -vDpropyP-l H-indole-3-carboxylate C793 [1233] Amount made: 2.2 mg. LCMS m/z 394 [M+H] ⁺ , purity (UV/MS) 94/74.

methyl 1 -f 3 -(4-(2-methoxyethyl)piperazin- 1 -yQpropy IV 1 H-indole-3-carboxylate C794

[1234] Amount made: 9.3 mg. LCMS m/z 360 [M+H] ⁺ , purity (UV/MS) 96/79.

methyl l-(3-(4-(2-methoxyphenyl)piperidin-l -vPpropy IVl H-indole-3-carboxylate C795

[1235] Amount made: 19.4 mg. LCMS m/z AQl [M+H] ⁺ , purity (UV/MS) 98/73.

methyl 1 -(3 -f 4-(2-morpholino-2-oxoethvDpiperazin- 1 -y Ppropyl)- 1 H-indole-3-carboxylate C796

[1236] Amount made: 15.7 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 94/79.

methyl l-(3-(4-(3-chlorophenyl)piperazin-l-yl)propyl>lH-indole-3 -carboxyIate C797

[1237] Amount made: 15.1 mg. LCMS m/z 412 [M+H] ⁺ , purity (UV/MS) 84/51.

methyl 1 -f 3-(4-(3-cvanopyridin-2-yl> 1 ,4-diazepan- 1 -vDpropy IV 1 H-indole-3-carboxylate

C798

[1238] Amount made: 5.8 mg. LCMS m/z 418 [M+H] ⁺ , purity (UVMS) 93/83.

methyl l-Q-(4-(4-chlorophenyl)piperazin- 1 -yPpropylM H-indole-3-carboxylate C799

[1239] Amount made: 15.5 mg. LCMS m/z 412 [M+H] ⁺ , purity (UV/MS) 80/48.

methyl 1 -(3-(4-(4-cyanophenyl)piperazin- 1 -yDpropylVl H-indole-3-carboxylate hydrochloride C800

[1240] Amount made: 5.5 mg. LCMS m/z 403 [M+H] ⁺ , purity (UV/MS) 100/100.

methyl l-f3-(4-(4-fluoro-2-nitrophenyl)piperazin-l-yI)propyl)-l H-indole-3-carboxylate

C801

[1241] Amount made: 22.0 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 77/47.

methyl l-f3-f4-f4-fluorophenoxy)piperidin-l-yl)propyl)-l H-indole-3-carboxylate hydrochloride C8Q2

[1242] Amount made: 17.5 mg. LCMS m/z 41 1 [M+H] ⁺ , purity (UV/MS) 95/86.

methyl l-f3-(4-(6-fluorobenzord1isoxazol-3-yl)piperidin-l-yl)propyl )-lH-indoIe-3- carboxylate C803

[1243] Amount made: 15.1 mg. LCMS m/z 436 [M+H] ⁺ , purity (UV/MS) 87/78.

methyl l-(3-f4-fpyrrolidin- 1 -yl)piperidin-l -yPpropyD-l H-indole-3-carboxylate C804

[1244] Amount made: 26.9 mg. LCMS m/z 370 [M+H] ⁺ , purity (UV/MS) 99/84.

methyl l-f3-C4-phenylpiperazin-l-yl)propyl)-lH-indoIe-3-carboxylate C805

[1245] Amount made: 17.5 mg. LCMS m/z 378 [M+H] ⁺ , purity (UV/MS) 87/68.

methyl l-(3-f4-phenylpiperidin-l-yl)propyl)-lH-indole-3-carboxylate C806

[1246] Amount made: 13.2 mg. LCMS m/z 371 [M+H] ⁺ , purity (UV/MS) 97/79.

methyl l-f3-(methylf2-(pyridin-2-yl ^' )ethvπamino ^" )propyl>lH-indole-3-carboxylate C8Q7

[1247] Amount made: 12.1 mg. LCMS m/z 352 [M+H] ⁺ , purity (UV/MS) 93/72.

1 -(3-((2-( 1 H-indol-3-vπethynfmethvnamino ^' jpropylVN-methoxy-N-methyl- 1 H-indole-3- carboxamide C808

[1248] Amount made: 0.8 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 80/60.

l -(3-(3.4-dihydroisoquinolin-2(lHVyπpropylVN,5-dimethoxy-N-m ethyl-lH-indole-3- carboxamide C809

[1249] Amount made: 23.2 mg. LCMS m/z 408 [M+H] ⁺ , purity (UV/MS) 100/66.

1 -(3-(3-acetamidopyrrolidin-l -vDpropyD-N-methoxy-N-methyl-l H-indole-3-carboxamide C810

[1250] Amount made: 7.3 mg. LCMS m/z 373 [M+H] ⁺ , purity (UV/MS) 88/70.

l-O-^-Q-rdiisopropylamino^ethvDpiperazin-l-yπpropylVN-me thoxy-N-methyl-lH-indole- 3-carboxamide C811

[1251] Amount made: 9.8 mg. LCMS m/z 458 [M+H] ⁺ , purity (UV/MS) 99/80.

l -(3-(4-(2-(dimethylamino')-2-oxoethyl)piperazin-l-yπpropyl' )-N-methoxy-N-methyl-lH- indole-3-carboxamide C812

[1252] Amount made: 11.8 mg. LCMS m/z 416 [M+H] ⁺ , purity (UV/MS) 94/85.

1 -(3-(4-(2-(dimethylamino)ethyl)piperazin- 1 -vQpropyD-N-methoxy-N-methyl- 1 H-indole-3- carboxamide C813

[1253] Amount made: 6.9 mg. LCMS m/z 402 [M+H] ⁺ , purity (UV/MS) 76/55.

l-(3-("4-(2-chlorophenvπpiperazin-l-yl ^* )propylVN,5-dimethoxy-N-methyl-lH-indole-3- carboxamide hydrochloride C814

[1254] Amount made: 7.2 mg. LCMS m/z 471 [M+H] ⁺ , purity (UV/MS) 90/70.

l-r3-r4-r2-chlorophenyl)piper-izin-l-yl ^' )propyl')-N-methoxy-N-methyl-lH-indole-3- carboxamide hydrochloride C815

[1255] Amount made: 2.3 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 90/79.

1 -f3-f 4-(2-ethoxyethyl)piperazin- 1 -vOpropylVN-methoxy-N-methyl- 1 H-indole-3- carboxamide C816

(1256] Amount made: 4.8 mg. LCMS m/z 403 [M+H] ⁺ , purity (UV/MS) 95/77.

1 -f3-f4-(2-hydroxyphenyl)piperazin-l -yl)propylVN,5-dimethoxy-N-methyl-l H-indole-3- carboxamide C817

[1257] Amount made: 7.1 mg. LCMS m/z 453 [M+H] ⁺ , purity (UV/MS) 89/70

1 -(3 -f 4-(2-hy droxyphenyPpiperazin- 1 -yPpropy lVN-methoxy-N-methy 1- 1 H-indole-3 - carboxamide C818

[1258] Amount made: 5.9 mg. LCMS m/z 423 [M-I-H] ⁺ , purity (UV/MS) 80/70.

1 -f3-(4-(3-chlorophenyl)piperazin-l -vOpropyiyN-methoxy-N-methyl-l H-indole-3- carboxamide C819

[1259] Amount made: 2.4 mg. LCMS m/z 441 [M+HJ ⁺ , purity (UV/MS) 86/76.

l-rS-^-fS-cyanopyridin^-ylVlλ-diazepan-l-yDpropyD-N-meth oxy-N-methyl-lH-indole-S- carboxamide C820

[1260] Amount made: 5.4 mg. LCMS m/z 447 [M+H] ⁺ , purity (UV/MS) 95/65.

l-(3-(4-(4-acetylphenyl)piperazin-l-yl)propylVN-methoxy-N -methyl-lH-indole-3- carboxamide C821

[1261] Amount made: 14.8 mg. LCMS m/z 449 [M+H] ⁺ , purity (UV/MS) 96/70.

1 -(3-(4-(4-chlorophenyl)piperazin-l -yl)propyl)-N-methoxy-N-methyl- 1 H-indole-3- carboxamide C822

[1262] Amount made: 1 1 A mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 90/70.

1 -( ^' 3-(4-(4-chlorophenylsulfonyl ^' )piperidin- 1 -vDpropylVN-methoxy-N-methyl- 1 H-indole-3- carboxamide hydrochloride C823

[1263] Amount made: 6.8 mg. LCMS m/z 504 [M+H] ⁺ , purity (UV/MS) 96/73.

1 -D-(4-( 4-chlorophenylthio)piperidin- 1 -yPpropyl)-N-methoxy-N-methy 1- 1 H-indole-3- carboxamide hydrochloride C824

[1264] Amount made: 8.4 mg. LCMS m/z 472 [M+H] ⁺ , purity (UV/MS) 97/72.

1 -(3-(4-(4-cy anophenvDpiperazin- 1 -vDpropylVN-rnethoxy-N-methyl- 1 H-indole-3- carboxamide hydrochloride C825

[1265] Amount made: 1.7 mg. LCMS m/z 432 [M+H] ⁺ , purity (UV/MS) 90/60.

l-(3-f4-(4-fluoro-2-nitrophenyl)pipera2in-l-y])propyI)-N- rnethoxy-N-methyl-lH-indole-3- carboxamide C826

[1266] Amount made: 1.6 mg. LCMS m/z 470 [M+H] ⁺ , purity (UV/MS) 84/55.

1 -(3-(4-(4-fluorophenoxy)piperidin-l -vDpropyiyN-methoxy-N-methyl-1 H-indole-3- carboxamide hydrochloride C827

[1267] Amount made: 10.9 mg. LCMS m/z 440 [M+H] ⁺ , purity (UV/MS) 90/70.

l -(3-(4-(4-fluorophenyl)piperazin-l-yl)propyl ^' )-N,5-dimethoxy-N-methyl-lH-indole-3- carboxamide C828

[1268] Amount made: 12.4 mg. LCMS m/z 455 [M+H] ⁺ , purity (UV/MS) 93/70.

l-f3-r4-r4-fluorophenyπpiperazin-l-yl)propylVN-methoxy-N -methyl-lH-indole-3- carboxamide C829

[1269] Amount made: 6.3 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 88/60.

l-f3-("4-ben2ylpiperidin-l-yπpropyl>-N,5-dimethoxy-N- methyl-lH-indole-3-carboxamide C830

[1270] Amount made: 18.6 mg. LCMS m/z 450 [M+H] ⁺ , purity (UV/MS) 98/70.

l-C3-f4-butylpiperidin-l-yl')propyl ^' )-N,5-dimethoxy-N-methyl-lH-indole-3-carboxamide C831

[1271 J ^' Amount made: 16.3 mg. LCMS m/z 416 [M+H] ⁺ , purity (UWMS) 100/84.

N,5-dimethoxy-N-methyl-l-f3-f4-(2-moφholino-2-oxoethyl ^' )piperazin-l-vπpropyl ^' )-lH- indole-3-carboxamide C832

[1272] Amount made: 20.4 mg. LCMS m/z 488 [M+H] ⁺ , purity (UV/MS) 95/60.

N,5-dimethoxy-N-methyl-l-r3-(4-(pyrrolidin-l -yl)piperidin-l-yl)propylVlH-indole-3- carboxamide C833

[1273] Amount made: 17.6 mg. LCMS m/z 429 [M+H] ⁺ , purity (UV/MS) 95/92.

N,5-dimethoxy-N-methyl-l-r3-( ^' 4-phenylpipera2in-l-vπpropylVlH-indole-3 -carboxamide C834

[1274] Amount made: 14.0 mg. LCMS m/z 437 [M+H] ⁺ , purity (UV/MS) 88/50.

N,5-dimethoxy-N-methyl-l -f3-(Octahydroisoquinolin-2π H ^" )-yl)propyl> 1 H-indole-3- carboxamide C835

[1275] Amount made: 15.0 mg. LCMS m/z 414 [M+H] ⁺ , purity (UV/MS) 95/67.

N-methoxy-l-r3-r4-r2-methoxyethyl ^' )piperazin-l-yl)propyl ^' )-N-methyl-lH-indole-3- carboxamide C836

[1276] Amount made: 9.4 mg. LCMS m/z 389 [M+H] ⁺ , purity (UV/MS) 96/82.

N-methoxy-N-methyl-1 -f3-(4-(Ttetrahvdrofuran-2-y0methv0piperazin-l -vDpropyIVl H- indole-3-carboxamide C837

[1277] Amount made: 8.1 mg. LCMS m/z 415 [M+H] ⁺ , purity (UV/MS) 95/81.

N-methoxy-N-methyl-l-C3-( ^' 4-C2-( ^' methylthio)phenyπpiperazin-l-vπpropyl>-l H-indole-3- carboxamide C838

[1278] Amount made: 6.0 mg. LCMS m/z 453 [M+H] ⁺ , purity (UV/MS) 86/70.

N-methoxy-N-methyl-l -( ^' 3-( ^' 4-( ^' 2-morpholino-2-oxoethvπpiρerazin-l-yl ^' )propyl>-lH-indole-3- carboxamide C839

[1279] Amount made: 13.7 mg. LCMS m/z 458 [M+H] ⁺ , purity (UV/MS) 95/73.

N-methoxy-N-methyl- 1 -(3-(4-(pyrrolidin- 1 -vQpiperidin- 1 -vDpropylV 1 H-indole-3- carboxamide C840

[1280] Amount made: 8.0 mg. LCMS m/z 399 [M+H] ⁺ , purity (UV/MS) 92/70.

N-methoxy-N-methyl- 1 -( 3-(4-phenylpiperidin- 1 -yDpropyiy 1 H-indole-3-carboxamide C841 [1281] Amount made: 4.1 mg. LCMS m/z 406 [M+H] ⁺ , purity (UV/MS) 96/80.

N-methoxy-N-methyl-l-(3-rmethyir2-fpyridin-2-yl ^' )ethyl)amino)proρyl ^' )-l H-indole-3- carboxamide C842

[1282] Amount made: 7.1 mg. LCMS m/z 381 [M+H] ⁺ , purity (UV/MS) 98/84.

l-(l-(3-(2.3-dihydro-lH-inden-2-ylamino)propylVlH-pyrrolo f2.3-b]pyridin-3-vn-2.2.2- trifluoroethanone C843

[1283] Amount made: 1.9 mg. LCMS m/z 388 [M+H] ⁺ , purity (UV/MS) 79/50.

l-(l-(3-(4-(3-chloro-5-{ ^' trifluoromethyl)pyridin-2-yl)piperazin-l-yl)propyl>-lH-py rrolo[2,3- b]pyridin-3-yl)-2,2.2-trifluoroethanone C844

[1284] Amount made: 2.6 mg. LCMS m/z 520 [M+H] ⁺ , purity (UV/MS) 98/80.

1 -( 1 -(3-(4-(2-C4-chlorophenoxy')ethyDpiperazin-l -vDpropylV 1 H-pyrrolof23-b]pyridin-3-vπ- 2,2,2-trifluoroethanone C845

[1285] Amount made: 1.8 mg. LCMS m/z 495 [M+H] ⁺ , purity (UV/MS) 99/80.

2,2,2-trifluoro- 1 -(I -C3-(2-phenoxyethylamino ^' )propyIH H-pyrrolo[2,3-b]pyridin-3- yPethanone C846

[1286] Amount made: 0.8 mg. LCMS m/z 392 [M+H] ⁺ , purity (UV/MS) 100/80.

2,2,2-trifluoro- 1 -( 1 -(3-(4-(2-phenoxyethv0piperazin- 1 -vDpropylV 1 H-pyrroIo[2,3-b1pyridin- 3-vπethanone C847

[1287] Amount made: 3.0 mg. LCMS m/z 461 [M+H] ⁺ , purity (UV/MS) 100/90.

2,2,2-trifluoro-l-π -(3-(4-phenethyl-M-diazepan-l-yl)propylVlH-pynOlor23-b1pyrid in-3- yHethanone C848

[1288] Amount made: 2.6 mg. LCMS m/z 459 [M+H] ⁺ , purity (UV/MS) 99/80.

blpyridin-3-yl)ethanone C849

[1289] Amount made: 2.2 mg. LCMS m/z 463 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -( 1 -(3-(4-(2,4-dichlorobenzy Dpiperazin- 1 -vDpropylV 1 H-pyrrolof 2,3-b ^" |pyridin-3-yI V2,2,2- trifluoroethanone C850

[1290] Amount made: 2.9 mg. LCMS m/z 499 [M+H] ⁺ , purity (UV/MS) 99/80.

2,2.2-trifluoro-l-(l -(3-f4-(3-(pyridin-4-ylVl,2,4-oxadiazol-5-vnpiperidin-l-vnpr opylVlH- pyrrolof2,3-b ^" |pyridin-3-yl)ethanone C851

[1291] Amount made: 3.1 mg. LCMS m/z 485 [M+H] ⁺ , purity (UV/MS) 99/90.

2.2.2-trifluoro- 1 -( 1 -(3-(4-(3-fpyridin-3-y IV 1 ,2,4-oxadiazol-5-vnpiperidin- 1 -yHpropyl V 1 H- pyrrolof2,3-blpyridin-3-vπethanone C852

[1292] Amount made: 1.9 mg. LCMS m/z 485 [M+H] ⁺ , purity (UV/MS) 99/90.

1 -(I -(3-(4-(3-chloro-5-(trifluoromethyl ^' )pyπdin-2-yl)piperazin- 1 -yQpropylV 1 H-pyrroio^J- b1pyridin-3-yI ^" )ethanone C853

[1293] Amount made: 0.6 mg. LCMS m/z 466 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-(4-(2-(4-chlorophenoxy)ethyl)piperazin-l -yl)propylVlH-pyrrolo| ^' 2,3-b]pyridin-3- vDethanone C854

[1294] Amount made: 1.6 mg. LCMS m/z 441 [M+H] ⁺ , purity (UV/MS) 100/80.

l-fl -f3-(4-f2-phenoxyethyl)piperazin-l-yl ^' )propyl ^' )-lH-pyrrolo[2,3-b]pyridin-3-yl ^' )ethanone C855

[1295] Amount made: 0.2 mg. LCMS m/z 407 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -(I -f3-(4-phenethyi-l,4-diazepan-l-yQpropylVl H-pyrrolor2,3-b]pyridin-3-vDethanone C856

[1296] Amount made: 0.7 mg. LCMS m/z 405 [M+H] ⁺ , purity (UV/MS) 100/80.

l-(l-π-(4-(4-fluorobenzyl)-l,4-dia2epan-l-yl)propyl>- lH-pyrrolor2,3-blpyridin-3- vHethanone C857

[1297] Amount made: 1.6 mg. LCMS m/z 409 [M+H] ⁺ , purity (UV/MS) 100/80.

1 -f 1 -(3-(4-(2,4-dichloroben2yl ^' )piperazin-l -vDpropylV lH-pyrrolor2,3-b]pyridin-3- vQethanone C858

[1298] Amount made: 0.7 mg. LCMS m/z 445 [M+H] ⁺ , purity (UV/MS) 100/80.

bipyridin-3-yl)ethanone C859

[1299] Amount made: 0.8 mg. LCMS m/z 431 [M+H] ⁺ , purity (UV/MS) 97/70.

l-π-f3-C4-G-rpyridin-3-vn-1.2,4-oxadiazol-5-ynpiperidin- l-vnpropylVlH-pyrrolor2,3- b1pyridin-3-yl)ethanone C860

[1300] Amount made: 0.2 mg. LCMS m/z 431 [M+H] ⁺ , purity (UV/MS) 99/70.

r-(3-r3-r2.2,2-trifluoroacetylVlH-pyrrolo| ^' 2,3-blpyridin-l-yl ^' )propyl ^' )spiro[ ^' chroman-2,4'- piperidinl-4-one C861

[1301] Amount made: 1.0 mg. LCMS m/z 472 [M+H] ⁺ , purity (UV/MS) 99/90.

l-π-(3-r4-r2-chlorobenzyn-1.4-diazepan-l-vnproϋylVlH-py rrolor2.3-b]pyridin-3-yn-2.2,2- trifluoroethanone C862

[1302] Amount made: 2.5 mg. LCMS m/z 479 [M+H] ⁺ , purity (UV/MS) 99/90.

l-(l-(3-C3-('4-chlorophenoxy)piperidin-l-yl)propylVlH-pyr rolof2,3-b1pyridin-3-vπ-2.2,2- trifluoroethanone C863

[1303] Amount made: 1.0 mg. LCMS m/z 466 [M+H] ⁺ , purity QJVMS) 99/90.

l-π-r3-(3-(2-chloroben2yπpiυeridin-l-vnpropyl')-lH-pyr rolof2.3-b1pyridin-3-ylV2.2.2- trifluoroethanone C864

[1304] Amount made: 0.8 mg. LCMS m/z 464 [M+H] ⁺ , purity (UV/MS) 100/90.

2.2.2-trifluoro-l-π-(3-(3-phenethyl-8-azabicvclor3.2.noc tan-8-vnpropylVl H-pyrrolor2.3- bipyridin-3-vπethanone C865

[1305] Amount made: 1.7 mg. LCMS m/z 470 [M+H] ⁺ , purity (UV/MS) 97/70.

1 -( 1 -f 3 -f 3 -(4-chlorophenethyl V8-azabicvclor3.2.11octan-8 -y Dpropyl V 1 H-pyrrolo ϊ2.3- b1pyridin-3-yO-2.2.2-trifluoroethanone C866

[1306] Amount made: 3.2 mg. LCMS m/z 504 [M+H] ⁺ , purity (UV/MS) 93/60.

l-d-fS-rS-Q^-chlorophenylVσ-oxoethylVδ-azabicvclofS^. lloctan-8-vnpropylVlH- pyrrolo[ ^" 2,3-b]pyridin-3-vπ-2.2,2-trifluoroethanone C867

[1307] Amount made: 2.6 mg. LCMS m/z 518 [M+H] ⁺ , purity (UV/MS) 94/80.

l-(l-(3-(4-(3-chlorophenoxy)piperidin-l-yl)propyl)-lH-pyr rolor2,3-blpyridin-3-yl)-2,2,2- trifluoroethanone C868

[1308] Amount made: 0.8 mg. LCMS m/z 466 [M+H] ⁺ , purity (UV/MS) 100/90.

2.2.2-trifluoro-l-π-(3-r3-r4-fluorophenoχy ^' )-8-azabicyclor3.2.1]octan-8-vnpropyl ^' )-l H- pyrroloPJ-bipyridin-S-yDethanone C869

[1309] Amount made: 0.9 mg. LCMS m/z 476 [M+H] ⁺ , purity (UV/MS) 100/70.

l-d-β-π-Q-chlorophenoxyVS-azabicvclofS^.lioctan-S-vπpr opylVlH-pyrrolopj- b1pyridin-3-ylV2.2.2-trifluoroethanone C870

[1310] Amount made: 1.7 mg. LCMS m/z 492 [M+H] ⁺ , purity (UV/MS) 100/90.

l-π-G-(4-(2-(4-chlorophenoxy')ethvπpiperidin-l-vπpropy lVlH-pyrrolor2.3-blpyridin-3-ylV 2.2.2-trifluoroethanone C871

11311] Amount made: 0.8 mg. LCMS m/z 494 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 1 -(3 -(4-(2-ChIQrObCnZvI)- 1 ,4-diazepan- 1 -yπpropyl V 1 H-pyrrolo [2, 3-b ^~ |pyridin-3 - vDethanone C872

[1312] Amount made: 1.7 mg. LCMS m/z 425 [M+H] ⁺ , purity (UV/MS) 90/50.

l -(l-(3-(3-(4-chlorophenoxy)piperidin-l-yl)propyl)-lH-pyrrolo [2.3-b|pyridin-3-yl)ethanone C873

[1313] Amount made: 0.3 mg. LCMS m/z 412 [M+H] ⁺ , purity (UV/MS) 100/90.

l-fl-(3-(3-(4-chlorophenethvπ-8-azabicvclo[3.2.11octan-8 -yl)propyl>lH-pyrrolo[2,3- blpyridin-3-yl)ethanone C874

[1314] Amount made: 1.7 mg. LCMS m/z 450 [M+H] ⁺ , purity (UV/MS) 100/80.

2-(8-(3-(3-acetyl-lH-pyrrolol2.3-b1pyridin-l-yl)propyl)-8-az abicvclo| ^' 3.2.11octan-3-yl)-l-(4- chlorophenvDethanone C875

[1315] Amount made: 1.6 mg. LCMS m/z 464 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(l-(3-(4-(3-chlorophenoxy)piperidin-l-yl)propyl)-lH-pyr rolor2,3-b]pyridin-3-yl)ethanone C876

[1316] Amount made: 1.5 mg. LCMS m/z 412 [M+H] ⁺ , purity (UV/MS) 99/90.

l-d^S^S^-fluorophenoxyVδ-azabicvclop.σ.1]octan-S-yπpro pylVlH-pyrrolopj- blpyridin-3-yl)ethanone C877

[1317] Amount made: 0.6 mg. LCMS m/z 422 [M+H] ⁺ , purity (UV/MS) 100/100.

l-(l-(3-(3-(2-chlorophenoxyV8-azabicyclo[3.2.11octan-8-yl )propylVlH-pyrrolo[2.3- b1pyridin-3-yl)ethanone C878

[1318] Amount made: 1.1 mg. LCMS m/z 438 [M+H] ⁺ , purity (UV/MS) 100/90.

l-π-(3-(4-f2-r4-chlorophenoxy ^' )ethvπpiperidin-l-vπpropyl>lH-pyrrolo| ^' 2,3-b]pyridin-3- vDethanone C879

[1319] Amount made: 0.8 mg. LCMS m/z 440 [MH-H] ⁺ , purity (UV/MS) 100/90.

l-O-^-O-chloro-S-ftrifluoromethvDpyridin-σ-yDpiperazin-l -yDpropylVy-methoxy-lH- indole-3-carbonitrile C880

[1320] Amount made: 4.5 mg. LCMS m/z 478 [M+H] ⁺ , purity (UV/MS) 100/100.

l-C3-( ^' 4-r2-r4-chlorophenoxy ^' )ethyl)piperazin-l-yπpropylV7-methoxy-lH-indole-3- carbonitrile C881

[1321] Amount made: 3.1 mg. LCMS m/z 453 [M+H] ⁺ , purity (UV/MS) 100/90.

7-methoxy- 1 -( 3-f4-f2-phenoxyethyl)piperazin- 1 -vDpropylVl H-indole-3-carbonitrile C882 [1322] Amount made: 3.2 mg. LCMS m/z 419 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3 -(4-f 4-fluorobenzy P- 1.4-diazepan- 1 -vOpropy l)-7-methoxy- 1 H-indole-3-carboni tri Ie C883

[1323] Amount made: 1.4 mg. LCMS m/z 421 [M+H] ⁺ , purity (UV/MS) 99/80.

l-r3-r4-r2.4-dichlorobenzyπpiperazin-l-yl)propyl)-7-meth oxy-lH-indole-3-carbonitrile C884

[1324] Amount made: 4,9 mg. LCMS m/z 457 [M+H] ⁺ , purity (UV/MS) 100/90.

l-(3-r4-(2-(4-chloronaphthalen-l-yloxy')ethyl)piperazin-l-yl )propyl ^' )-7-methoxy-lH-indole-3- carbonitrile C885

[1325] Amount made: 1.0 mg. LCMS m/z 503 [M+HJ ⁺ , purity (UV/MS) 100/100.

7-methoxy-l-r3-(4-(3-(pyridin-4-yl ^' )-1.2.4-oxadiazol-5-yl)piperidin-l-yπproρyl)-lH-indole-3- carbonitrile C886

[1326] Amount made: 4.0 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 100/90.

y-methoxy-l-O-^-π-Cpyridin-S-ylVl^^-oxadiazol-S-yπpiper idin-l-yDpropylVlH-indole-S- carbonitrile C887

[1327] Amount made: 3.9 mg. LCMS m/z 443 [M+H] ⁺ , purity (UV/MS) 99/80.

y-methoxy-l-O-^-C∑-oxoindolin-l-vπpiperidin-l-vπpropylVl H-indole-S-carbonitrile C888 [1328] Amount made: 2.6 mg. LCMS m/z 429 [M-J-H] ⁺ , purity (UV/MS) 93/80.

y-methoxy-l-O-^-oxospirorchroman-∑λ'-piperidineT-r-vπ propyD-lH-indole-S-carbonitrile C889

11329] Amount made: 2.3 mg. LCMS m/z 430 [M+H] ⁺ , purity (UV/MS) 100/100.

l-('3-(4-(2-chlorobenzyl)-l,4-diazepan-l-yl)propyl)-7-met hoxy-lH-indole-3-carbonitrile C890

[1330] Amount made: 3.1 mg. LCMS m/z 437 [M+H] ⁺ , purity (UV/MS) 97/80.

l-(3-(3-(4-chlorophenoxy ^' )piperidin-l-yl)propyl ^' )-7-methoxy-l H-indole-3-carbonitrile C891 [1331] Amount made: 3.4 mg. LCMS m/z 424 [M+H] ⁺ , purity (UV/MS) 100/90.

l-r3-(3-(2-chlorobenzyl)piperidin-l -yl)propyl ^' )-7-methoxy-lH-indole-3-carbonitrile C892

[1332] Amount made: 3.8 mg. LCMS m/z 422 [M+H] ⁺ , purity (UV/MS) 100/100.

7-methoxy-l-(3-r3-phenethyl-8-azabicvclo[3.2.noctan-8-yl) propyl>-lH-indole-3-carbonitrile C893

[1333] Amount made: 2.6 mg. LCMS m/z 428 [M+H] ⁺ , purity (UV/MS) 94/80.

l-(3-(3-(4-chlorophenethyl)-8-azabicvclo[3.2.1]octan-8-y� �propyl)-7-methoxy-l H-indole-3- carbonitrile C894

[1334] Amount made: 4.3 mg. LCMS m/z 462 [M+H] ⁺ , purity (UV/MS) 98/80.

l -('3-(3-( ^' 2-(4-chloroρhenylV2-oxoethyl)-8-azabicvclo[ ^' 3.2.1]octan-8-yl)propyl>-7-methoxy- lH-indole-3-carbonitrile C895

[1335] Amount made: 5.2 mg. LCMS m/z 476 [M+H] ⁺ , purity (UV/MS) 98/80.

1 -(3-(4-f3-chlorophenoxy')piperidin- 1 -v0propyl>7-methoxy-l H-indole-3-carbonitrile C896 [1336] Amount made: 4.0 mg. LCMS m/z 424 [M+H] ⁺ _s purity (UV/MS) 100/100.

l-O-O-^-fluorophenoxyVδ-azabicyclorS.σ.1]octan-δ-yπpr opylVy-methoxy-lH-indole-S- carbonitrile C897

[1337] Amount made: 3.2 mg. LCMS m/z 434 [M+H] ⁺ , purity (UV/MS) 95/80.

1 -(3-C3-r2-chlorophenoxyy8-azabicyclo[3.2.1 ^~ |octan-8-y0propyl>7-methoxy- 1 H-indole-3- carbonitrile C898

[1338] Amount made: 3.5 mg. LCMS m/z 450 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -(3 -(4-f 2-(4-chlorophenoxy ^' )ethy Opiperidin- 1 -y l')propylV7-methoxy- 1 H-indole-3 - carbonitrile C899

[1339] Amount made: 1.2 mg. LCMS m/z 452 [M+H] ⁺ , purity (UV/MS) 100/90.

1 -( 1 -f 3-(4-buty lpiperidin- 1 -vOpropylV 1 H-indol-3-yPethanone C900

[1340] Amount made: 16.2 mg. LCMS m/z 341 [M+H] ⁺ , purity (UV/MS) 99/100.

l-d-r3-r6-methoxy-3,4-dihydro-lH-pyridor3.4-blindol-2(9HV ynDroDylVlH-indol-3- vHethanone C901

[1341] Amount made: 3.0 mg.XCMS m/z 402 [M+H] ⁺ , purity (UV/MS) 100/82.

l-(7-methoxy-l-(3-( ^' 4-(3-( ^> trifluoromethyπpyridin-2-yπpipera2in-l-yπpropylVl H-indol-3- yHethanone C902

[1342] Amount made: 9.6 mg. LCMS m/z 463 [M+H] ⁺ , purity (UV/MS) 91/60.

N-d-(3-r3-acetyl-7-methoxy-lH-indol-l-yl)propyπpyrrolidi n-3-ylVN-methylacetamide C903

[1343] Amount made: 6.4 mg. LCMS m/z 374 [M+H] ⁺ , purity (UV/MS) 90/60.

8-(3-(3-acetyl-7-methoxy-l H-indol- 1 -yQρropyl> 1 -phenyl- 1 ,3,8-triazaspiror4.51decan-4-one C904

[1344] Amount made: 1.1 mg. LCMS m/z 463 [M+H] ⁺ , purity (UV/MS) 82/60.

N-Cl -(3-(3-acetvI-7-methoxy-l H-indol-1 -yl)propyl)piperidin-4-yπ-N- cyclopropylbenzenesulfonamide C9Q5

[1345] Amount made: 9.1 mg. LCMS m/z 512 [M+H] ⁺ , purity (UV/MS) 94/50.

General procedure for substitution on the tail (GP2): 1-f 1 -r3-[3-butyl-8-aza- bicvcloD^.ljoctan-S-yljpropyπ-lH-indol-3-ynethanone

[1346] l-[l-(3-chloropropyl)-lH-indol-3-yl]-ethanone (12 mg, 0.05 mmol), cesium carbonate (32 mg, 0.1 mmol), potassium iodide (8 mg, 0.05 mmol) and 5-butyl-2- azabi-cyclo[2.2.1]heptane (6 mg, 0.04 mmol) were weighed into a vial, dry MeCN (1 mL) was added and the reaction mixture was shaken at 80 ⁰ C on a shaker over night. The product was purified by SCX to yield the title compound.

[1347] LC/MS purity: UV/MS 88/67

1 -[I -f2-[3-(cyclopropylmethoxy)-8-azabicyclor3.2.11oct-8-yl]prop yl]-l/y-indol-3-yl1- ethanone

[1348] Prepared according to GP2 from l-[l-(3-chloropropyl)-lH-indol-3-yl]- ethanone (12 mg, 0.05 mmol), cesium carbonate (32 mg, 0.1 mmol), potassium iodide (8 mg, 0.05 mmol) and 3-(cyclopropylmethoxy> 8-azabicyclo[3.2.1]octane (7 mg, 0.04 mmol).

[1349] LC/MS purity: UV/MS 99/88

General procedure for amide formation (GP3): N-phenyl-lH-indole-3-carboxamide

[1350] Indole-3-carboxylic acid (644 mg, 4 mmol), 1-hydroxybenzothiazole (810 mg, 6 mmol), l-ethyl-3-(3-dimethylaminopropyl)carboiimde hydrochloride (1.15 g, 6 mmol), DMAP (5 mg, 0.04 mmol), triethyl amine (1.84 g, 18 mmol) and 4-chlorobenzyl amine (566 mg, 4 mmol) were weighed into a MW vial, dry MeCN (10 mL) was added, and the reaction heated in the MW at 140 ⁰ C for 15 min. The reaction mixture was diluted with EtOAc and washed with water and brine, dried over sodium sulphate, filtered and concentrated in vacuo. The product was recrystallized from methanol. Yield: 733 mg (65%).

Receptor Selection and Amplification Technology (R-SAT) Assay

[1351] The functional receptor assay, Receptor Selection and Amplification Technology (R-SAT), was used to investigate the pharmacological properties of novel compounds. R-SAT is disclosed in U.S. Patent Nos. 5,707,798, 5,912,132, and 5,955,281 , all of which are hereby incorporated herein by reference in their entirety, including any drawings. These experiments have provided a molecular profile, or fingerprint, for each of these agents.

[1352] Briefly, NIH3T3 cells were grown in 96 well tissue culture plates to 70- 80% confluence. Cells were transfected for 16-20 h with plasmid DNAs using Polyfect (Qiagen Inc.) using the manufacturer's protocols. R-SATs were generally performed with 20 ng/well of receptor, 10 ng/well of RGS l (Burstein et al, JPET, 315:1278-1287) and 20 ng/well of β-galactosidase plasmid DNA. All receptor constructs used were in the pSI- derived mammalian expression vector (Promega Inc). The Ghrelin receptor genes were amplified by PCR from genomic DNA using oligodeoxynucleotide primers based on the published sequences. For large-scale transfections, cells were transfected for 16-20 h, then trypsinized and frozen in DMSO. Frozen cells were later thawed, plated at ~20,000 cells per well of a 96 half-area well plate that contained drug. With both methods, cells were then grown in a humidified atmosphere with 5% ambient CO ₂ for five days. Media was then

removed from the plates and marker gene activity was measured by the addition of the β- galactosidase substrate o-nitrophenyl β-D-galactopyranoside (ONPG) in PBS with 0.5% NP- 40. The resulting colorirnetric reaction was measured using a spectrophotometry plate reader (Titertek Inc.) at 420 nm. All data was analyzed using the XLFit (IDBSm) computer program. pICso represents the negative logarithm of the concentration of ligand that caused 50% inhibition of the constitutive receptor response. Percent inhibition was calculated as the difference between the absorbance measurements in the absence of added ligand compared with that in the presence of saturating concentrations of ligand normalized to the absorbance difference for the reference ligand (Substance P analog), which was assigned a value of 100%.

[1353] Data presented in Figure 1 are derived from R-SAT assays as previously described (Jensen, A., A. et. al. (2000). J Biol Chem. 275(38): 29547-55). The concentration response relationship of the reference antagonist/inverse agonist Substance P analog (open triangles), l-(l -(3-(4-(4-chlorophenoxy)piperidin-l-yI)propyl)-lH-indol-3-yl )ethanone (+ signs) and l -(l-(3-(4-butylpiperidin-l-yl)propyl)-lH-indol-3-yl)ethanone (open circles) to suppress constitutive activity of human Ghrelin receptors is shown. Data are plotted as response in absorbance units. Ligand activity is reported as -pICso, and percent inhibition relative to the reference antagonist/inverse agonist Substance P analog. Compounds of Formula I displayed potent ghrelin receptor antagonist/inverse agonist activity as disclosed in Figure 1 and Appendix A. These compounds are ghrelin receptor antagonists/inverse agonists in this system.

Phosphatidyl Inositol hydrolysis assays (PI assays)

[1354] To confirm the observation that these compounds display ghrelin receptor inverse agonist activity, a PI hydrolysis assay was performed, the results of which are disclosed in Figure 2. Data presented in Figure 2 are derived from PI assays performed as described in (Jensen, A. A. et. al. (2000). J Biol Chem. 275(38): 29547-55). The concentration response relationship of the reference agonist GHRP-6 (filled triangles), the reference antagonist/inverse agonist Substance P analog (filled circles) and l-(l-(3-(4- butylpiperidin-l -yl)propyl)-l H-indol-3-yl)ethanone (filled squares) to modulate the activity of human ghrelin receptors is shown. Data are plotted as the normalized response to basal

activity (receptor activity in the absence of added ligands) versus drug concentration. Potency is reported as -pECso values for GHRP-6, -pICso values for substance P analog and l-(l-(3- (4-butylpiperidin-l-yl)propyl)-l H-indol-3-yl)ethanone; and response is reported as that relative to the basal response in the absence of added ligands. Thus, two distinct in vitro functional assays confirm that analogs of Formula I possess potent antagonist/inverse agonist activity at human ghrelin receptors.

Suppression of acute feeding response in fasted rats

[1355] To confirm aspects of this molecular profile in vivo, l-(l-(3-(4- butylpiperidin-l-yl)propyl)-lH-indol-3-yl)ethanone, the reference antagonist/inverse agonist Substance P analog, and the reference antagonist D-Lys3-GHRP-6 were administered intraperitoneally to rats, and the ghrelin receptor mediated stimulation of feeding was determined essentially as described previously (Sartor O, et al. Endocrinology. 1985 Oct; 1 17(4): 1441 -7), and this is disclosed in Figure 3. Robust suppression of feeding was observed, at a dose of 30 mg/kg. This confirms that l-(l-(3-(4-butylpiperidin-l-yl)propyl> lH-indol-3-yl)ethanone functions as a ghrelin receptor antagonist in-vivo.

¹²⁵ I-ehrelin binding assay

[1356] To confirm the observation that these compounds bind to the ghrelin receptor, and can antagonize or block the binding of the endogenous GHSRIa agonist ghrelin, a binding assay was performed, the results of which are disclosed in Appendix B. Data presented in Appendix B is derived from binding assays performed as follows: 15cm dishes were seeded with 4 million HEK293 cells in 16ml 10% FCS/1% PSG/DMEM for transfection the next day. Plasmid DNA containing the GHSRIa receptor (12.5ug/dish) in 0.675ml DMEM was transfected into the cells by mixing with 180ul PolyFect, 15min later, mixing in 2.25ml 10% CS/DMEM, and transferring the mixture into the dish. At 16-18h post transfection, medium was replaced with 25ml fresh 10% FCS/1% PSG/ DMEM to each dish for another 18-2Oh. At approximately 48 hours post-transfection, cells were harvested in ice- cold membrane buffer (20 mM HEPES, 6 mM MgC12, 1 mM EDTA, pH to 7.2) using a cell scraper, and pelleted by centrifugation.

[1357] Pelleted cells were added to a nitrogen cavitation chamber and 900 bar of pressure applied for 30 min. The pressure was slowly released the cavitated cells collected in 50 ml falcon tubes. The tubes were centrifuged at 1000 rpm, 4°C for 10 min, and the supernatant collected. This centrifugation and collection was repeated two more times until the supernatant was free of precipitate (membranes are still in suspension). The supernatant was poured into a 50 ml centrifuge tube and centrifuged at 10.000 rpm, 4°C for 20 min. The supernatant was discarded and the pellet re-suspended in 750 μl membrane binding buffer using a chilled 1 ml syringe with 25G5/8 needle to re-suspend membranes. The protein concentration was determined using the BioRad Protein Assay Dye Reagent according to the manufacturers instructions. The protein concentration was adjusted to 5mg/ml and aliquots snap-frozed and stored at -80C until use.

[1358] Membranes were thawed rapidly; diluted with binding buffer (25mM Hepes+ 5mM MgC12, ImM CaCl ₂ , 2.5mM EDTA and 0.2% BSA) to a protein concentration of 0.8ug/30ul and placed on ice. 96-well plates (U-bottom wells) were prepared with serial dilutions (8doses, 40ul/w) of the test compounds. Membranes (30 uL/well) were then added, and incubated with test ligands for 30 min at room temperature wth shaking. 30ul ¹²⁵ I- ghrelin (0.053nM) was then added to each well, and the plates incubated for another 2.5 hours with shaking. Binding was terminated by filtration through GF/B filters (presoaked with 0.1% polyethylenimine) with a Brandel 96-well harvester. The filters were washed with ice-cold binding buffer (150ml/plate) and allowed to air-dry for 30min. 50ul MicroScient-20 cocktail was added to each dried well, the plates were sealed, and counted for 2min/well using a TopCount scintillation counter (Packard).

[1359] All data was analyzed using the Prizm computer program. pKi represents the negative logarithm of the concentration of ligand that caused 50% displacement of bound ^12s I-ghrelin adjusted for the concentration of radioligand using the Cheng-Prussoff equation: Ki=IC5o/{l+[test ligand]/Kdghreiιn} to derive Ki values. Percent inhibition was calculated as the difference between the bound ^l25 I-ghrelin in the absence of added ligand compared with that in the presence of saturating concentrations of ligand normalized to the absorbance difference for the reference ligand (ghrelin), which was assigned a value of 100% (not shown).

[1360] Although the invention has been described with reference to the above examples, it will be understood that modifications and variations are encompassed within the spirit and scope of the invention. Accordingly, the invention is limited only by the following claims.

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