PIPERIDINES AS INHIBITORS OF llβ-H YDROXYSTEROI D DEHYDROGENASE TYPE 1

FIELD OF INVENTION

The present invention relates to substituted piperidine compounds of the general formula (I) their tautomeric forms, their stereoisomers, their pharmaceutically accepted salts, or prodrugs thereof. The invention also relates to process for the manufacture of said compounds, and pharmaceutical compositions containing them and their use.

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(D

BACKGROUND OF THE INVENTION

Glucocorticoids play an important role in a variety of physiologic functions including immune and inflammatory responses, stress responses, aspects of development and metabolism. Glucocorticoids (Cortisol in human and corticosterone in rodents) are counter regulatory hormones, i.e. they oppose the action of insulin. {Dallman MF et al, 1993, Front Neuroendocrinal., 14, 303-47). Also, glucocorticoids regulate the expression of hepatic enzymes involved in gluconeogenesis and increase substrate supply by releasing glycerol from adipose tissue (increase in lipolysis) and amino acids from muscles (decrease in protein synthesis and increase in protein degradation). Glucocorticoids are also important in differentiation of pre-adipocytes into mature adipocytes, which are able to store triglycerides {Bujalska et al, 1999, Endocrinology, 140, 3188-3196).

Being so important, obviously, secretion of these glucocorticoids is tightly regulated by negative feedback loop controlled by hypothalamus-pituitary-adrenal (HPA) axis. While intracellular glucocorticoid levels are regulated by l lβ- hydroxysteroid dehydrogenases. There are two isoforms cloned and characterized of 1 lβ-HSDs viz. Type 1 and type 2 (Agarwal AK et al, 1989, J. Biol. Chem., 264, 18939- 943 and Albiston, AL et al, 1994, MoI. Cell Endocrinol, 105, Rl 1-1 T). l lβ-HSD type 1 is NADP(H) dependent enzyme that acts as a reductase in intact cells. It converts

cortisone (dehydrocorticosterone in rodents) to active Cortisol (corticosteroid in rodents). l lβ-HSDl is expressed in metabolically active tissues like liver, adipose tissue, and skeletal muscle. l lβ-HSDl potentiates glucocorticoid action by increasing their local concentration. l l β-HSD type 2 is NAD(H) dependent enzyme and it is unidirectional and oxidizes Cortisol (in human) and corticosterone (in rodents) to inactive cortisone and dehydrocorticosterone respectively. However, l l β-HSDl is widely expressed, 11 β-HSD2 is expressed only in tissues like kidney, placenta, gut where mineralocorticoid receptors are expressed. By converting active glucocorticoid to its inactive form, 1 1 β-HSD2 protects mineralocorticoid receptor (Chapman, KE et al, 1996, Biochem J., 313, 1007-1 T).

In Cushing's syndrome, circulating levels of glucocorticoids are elevated and shows similar but more profound symptoms as compared to Metabolic Syndrome (Arnaidi, G et al, 2003, J. Clin. Endocrinol. Metabol, 88, 5593-5602). However, in Metabolic Syndrome, circulating glucocorticoid levels are not elevated but intracellular glucocorticoid levels are elevated (Fraser, R e al., 1999, Hypertension, 33, 1364-68). Cushing's syndrome can be reversed by normalization of glucocorticoid levels (Watanabe, K. et al, 1988, Arch. Intern. Med., 148, 1358-60, McEwen, BS, 2002, J. Clin. Endocrinol. Me tab., 87, 1947-48). Based on this literature, it is tempting and logical too to speculate that Metabolic Syndrome is driven by higher intracellular levels of glucocorticoids and could be treated by suppression of their action. l lβ-HSDl knock-out mice show attenuated glucocorticoid-induced activation of gluconeogenic enzymes in response to fasting and lower plasma glucose levels in response to stress or obesity (Kotelevtse V. et al., 1997, Proc. Natl. Acad ScL 94,

14924-29). The study indicates that inhibition of l lβ-HSDl is useful in lowering plasma glucose and hepatic glucose production in type 2 diabetes. Another study

{Morton NMet al, 2001, J. Biol. Chem., 276, 41293-41300) indicates that, l lβ-HSDl knock-out mice express an anti-atherogenic lipoprotein profile, having low triglycerides, increased HDL cholesterol and increased apo-lipoprotein AI levels.

Again, this study indicates that, inhibition of l lβ-HSDl is useful in the treatment of atherosclerosis, dyslipidaemia of Metabolic Syndrome.

The most convincing demonstration of the link between the Metabolic Syndrome and l lβ-HSDl comes from the recent studies of transgenic mice overexpressing l lβ- HSD type 1 selectively in adipose tissue. These mice have increased adipose levels of

corticosterone and developed visceral obesity. The mice also showed pronounced insulin-resistant diabetes, hyperlipidaemia, hyperphagia despite hyperinsulinemia.

Thus, inhibition of l l β-HSDl could provide effective strategy to combat Metabolic Syndrome. WO01/90091 discloses the probable use of 1 lβ-HSDl inhibitors for the treatment of cardiovascular risk factors, osteoporosis, and glaucoma. It has also been stated that inhibition of 1 lβ-HSDl will have beneficial effect in pancreas for diabetes treatment.

US2005/0119266 discloses pyrrolidine and piperidine derivatives. These compounds may be used as inhibitors of trypsin-like serine proteases, specifically factor XA. This disclosure also describes the methods of using these compounds as anticoagulant agents for the treatment of thromboembolic disorders. WO97/18813 discloses peptidomimetic piperidine, 1 ,4-dihydropyridine, 1,2,3,4-tetrahydropyridine compounds and are useful in the inhibition of farnesyl-protein transferase and the farnesylation of oncogene protein Ras. WO 96/31503 discloses N-substituted azaheterocyclic carboxylic acids and esters thereof. These compounds may be useful clinically for the treatment of pain, hyperalgesic and/or inflammatory conditions.

However, the therapeutic potential of these compounds to treat diseases has not yet been proved and so there remains the need to develop newer medicines which are better or of comparable efficacy with the present treatment regimes, have lesser side effects and require a lower dosage regime

We herein disclose novel compounds of general formula (I) which are are inhibitors of 1 lβ -hydroxy steroid dehydrogenase Type 1 (1 lβ-HSDl) and are useful for the prevention and treatment of diseases states mediated by 1 lβ-HSDl. SUMMARY OF THE INVENTION The present invention discloses piperidine compounds as defined by the general formula (V) that are inhibitors of l lβ-hydroxysteroid dehydrogenase Type 1 (l lβ- HSDl) and are useful for the prevention and treatment of disease states mediated by l lβ-HSDl. The compounds of the present invention are useful in the treatment of human or animal body, by inhibition of l lβ-HSDl. The compounds of this invention are therefore suitable for the prevention and treatment of disease states mediated by l lβ-HSDl.

EMBODIMENT(S) OF THE INVENTION

An embodiment of the present invention provides piperidine substituted compounds represented by the general formula (1), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, and pharmaceutical compositions containing them or their mixtures thereof.

In a further embodiment of the present invention is provided pharmaceutical compositions containing compounds of the general formula (T), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, or their mixtures in combination with suitable carriers, solvents, diluents and other media normally employed in preparing such compositions.

In a still further embodiment is provided the use of piperidine compounds of the present invention as l lβ-HSDl inhibitors, by administering a therapeutically effective and non-toxic amount of compounds of general formula (1) or their pharmaceutically acceptable compositions to the mammals. DESCRIPTION OF THE INVENTION

Accordingly, the present invention relates to compounds of the general formula (T) represented below:

(D r wherein: X is selected from S(O) ₂ , -NH-S(O) ₂ , -CH ₂ -S(O) ₂ ;

Y is selected from C^^alkyl, C _(2-6) alkenyl, C _(2-6) alkynyl, carbocyclyl, heteroaryl, heterocyclyl wherein Y may be optionally substituted with (R ⁵ ) _n ; wherein n is an integer 0-5 and R ⁵ at each occurrence, independently represents a substituent on carbon selected from aryl, aryloxy, trifiuoromethyl, halogen, nitro, cyano, hydroxy, trifluυrυmelhoxy, urnino, carboxylamino, alkoxycarbonyl, alkylthiυ, alkylsufυnyl, alkylsulfinyl groups;

R and R may be same or different and independently represents hydrogen, Q _{1- 6} )alkyl, C ₍₂ - ₆ )alkenyl, C( _2-6) alkynyl, carbocyclyl, heteroaryl, heterocyclyl groups, wherein each of R ¹ and R ² may be optionally substituted with (R ⁵ ) _n wherein R ⁵ and 'n'

is as defined earlier, alternatively, R ¹ and R ² together with the nitrogen atom to which they are attached may form a 3-7 membered cylic ring optionally containing from 1 -3 heteroatoms selected from S, N, O; alternatively any one of R ¹ or R ² represents the group -C(O)-R ⁶ wherein R ⁶ is selected from adamantyl, alkyl, aryl, arylalkyl, alkylheterocyclyl groups, each of those groups may further be substituted with (R ⁵ ),,, wherein R ⁵ and 'n' are as defined earlier;

R ³ represents hydrogen, C(i _-6 )alkyl, C ₍₂ . ₆₎ alkenyl, C _(2-6) alkynyl, carbocyclyl, heterocyclyl wherein R ³ may be optionally substituted with (R ⁵ ) _n , wherein R ⁵ and n are as defined earlier; The invention further includes suitable pharmaceutically accepted salts, hydrates and solvates thereof.

In a preferred embodiment, the groups, radicals described above may be selected from: "Alkyl", as well as other groups having the prefix "alk", such as alkoxy and alkanoyl, means carbon chain which may either be linear or branched, and combinations thereof, unless the carbon chain is defined otherwise. Examples of alkyl group include but not limited to methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert.- butyl, pentyl, hexyl etc. Where the specified number of carbon atoms permits e.g. from C ₃ - io, the term alkyl also includes cycloalkyl groups, and combinations of linear or branched alkyl chains combined with cycloalkyl structures. When no number of carbon atoms is specified, Ci _-6 is intended.

"Alkenyl" means carbon chains which contain at least one carbon-carbon double bond, and which may be linear or branched or combinations thereof, unless the carbon chain is defined otherwise. Examples of alkenyl include but not limited to vinyl, allyl, isopropenyl, hexenyl, pentenyl, heptenyl, 1-propenyl, 2-butenyl, 2-methyl-2-butenyl etc. Where the specified number of carbon atoms permits, e. g., from C _5- I ₀ , the term alkenyl also includes cycloalkenyl groups and combinations of linear, branched and cyclic structures. When no number of carbon atoms is specified, Q _2-6 ) is intended.

"Alkynyl" means carbon chains which contain at least one carbon-carbon triple bond, and which may be linear or branched or combinations thereof. Examples of alkynyl include ethynyl, propargyl, 3-methyl-l -pentynyl etc. When no number of carbon atoms is specified, C ₍₂ ^ ₎ is intended.

As used herein, "carbocycle" or "carbocyclic residue" is intended to mean any stable monocyclic or bicyclic or tricyclic ring, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to,

cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, . [4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin). In a broader perspective, the term carbocycle is intended to include, wherever applicable, the groups representing cycloalkyl, phenyl and other saturated, partially saturated or aromatic residues;

"Cycloalkyl" is the subset of alkyl and means saturated carbocyclic ring having a specified number of carbon atoms, preferably 3-6 carbon atoms. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl etc. A cycloalkyl group generally is monocyclic unless otherwise stated. Cycloalkyl groups are saturated unless and otherwise stated.

The "alkoxy" refers to the straight or branched chain alkoxides of the number of carbon' atoms specified.

The tenii "alkylthio" refers to straight or branched chain alkylsulfides of the number of carbon atoms specified.

The term "alkylamino" refers to straight or branched alkylamines of the number of carbon atoms specified.

The term "alkylsulfonyl" refers to the straight or branched chain alkylsulfones of the number of the carbon atoms specified. The term "alkyl sulfinyl" refers to the straight or branched chain alkylsulfoxides of the number of the carbon atoms specified.

"Aryl" means a mono- or polycyclic aromatic ring system cotaining carbon ring atoms. The preffered aryls are monocyclic or bicyclic 6-10 membered aromatic ring systems. Phenyl and naphthyl are preferred aryls. "Heterocycle" and "heterocyclyl" refer to saturated or unsaturated non-aromatic rings or ring systems containing at least one heteroatom selected from O, S, N further including the oxidized forms of sulfur, namely SO and SO ₂ . Examples of heterocycles include tetrahydrofuran (THF), dihydrofuran, 1,4-dioxane, morpholine, 1,4-dithiane, piperazine, piperidine, 1,3-dioxolane, imidazoline, imidazolidine, pyrrolidine, pyrrυlinc, tctrahydropyran, dihydropyran, oxathiolane, dithiolane, 1,3-dioxane, 1,3- dithiane, oxathiane, thiomorpholine etc.

"Hetcroaryl" means an aromatic or partially aromatic heterocycle that contains at least one ring heteroatom selected from O, S and N. Heteroaryls thus include heteroaryls fused to the other kinds of rings, such as aryls, cycloalkyls, and

heterocycles that are not aromatic. Examples of heteroaryl groups include; pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, oxazolyl, oxadiazolyl, thiadiazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, triazinyl, thienyl, pyrimidyl, benzisoxazolyl, benzoxazolyl, benzthiazolyl, benzothiadiazolyl, dihydrobenzofuranyl, indolinyl, pyridazinyl, indazolyl, isoindolyl, dihydrobenzothienyl, indolinyl, pyridazinyl, indazolyl, isoindolyl, dihydrobenzothienyl, indolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, napthyridinyl, carbazolyl, benzodioxolyl, quinoxalinyl, purinyl. furazanyl, isobenzylfuranyl, benzimidazolyl, benzofuranyl, benzothienyl, quinolyl, indolyl, isoquinolyl, dibenzofuranyl etc. For heterocyclyl and heteroaryl groups, rings and ring systems containing from 3-15 carbon atoms are included, forming 1-3 rings.

"Halogen" refers to fluorine, chlorine, bromine, iodine. Chlorine and fluorine are generally preferred.

"earboxylamino" refers to carboxylic ester of amino group. Suitable groups and substituents on the groups may be selected from those described anywhere in the specification.

The term "substituted," as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. The term "substituted," as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound.

The compounds of structural formula (I) may be separated into their individual diastereoisomers by, for example, fractional crystallization from suitable solvent, for example ethanol or ethyl acetate or mixture thereof, or via chiral chromatography using an optically active stationary phase. Absolute stereochemistry may be established with

X-ray crystallography of crystalline products or crystalline intermediates, which are derivatized, if necessary, with a reagent containing an asymmetric center of known absolute configuration.

An aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein X is either selected from S(O) ₂ or -NH-S(O) ₂ . Within this subset, all other definitions are as originally defined with respect to formula (I).

An another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein Y is selected from carbocyclyl, heteroaryl, heterocyclyl

Within this subset, all other definitions are as originally defined with respect to formula (I).

More particularly, an another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein Y is selected from aryl, heteroaryl. Within this subset, all other definitions are as originally defined with respect to formula (I). Even more particularly, an another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein Y is aryl. Within this subset, all other definitions are as originally defined with respect to formula (I).

An another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein R ¹ and R ² may be same or different and selected independently from hydrogen, carbocyclyl, heteroaryl, heterocyclyl groups.

Within this subset, all other definitions are as originally defined with respect to formula

(I)- Particularly, an another aspect of the present invention that is of interest relates to the compounds of formula (1) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein R ¹ and R ² may be same or different and selected independently from hydrogen, aryl, heteroaryl groups. Within this subset, all other definitions are as originally defined with respect to formula (I). More particularly, an another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein R ¹ and R ² may be same or different and selected independently from hydrogen, C _(1-4) alkyl, aryl groups. Within this subset, all other definitions are as originally defined with respect to formula (I). An another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein R ¹ and R ² together with the nitrogen atom to which they are attached may form a 3-7 membered cyclic ring optionally containing 1-3 heteroatoms

selected from S, N, O. Within this subset, all other definitions are as originally defined with respect to formula (I).

An another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein any of R ¹ or R ² represents the group -C(O)R ⁶ wherein R ⁶ is selected from alkyl, aryl, arylalkyl groups. Within this subset, all other definitions are as originally defined with respect to formula (I).

An another aspect of the present invention that is of interest relates to the compounds of formula (I) as well as pharmaceutically accepted salts, hydrates and solvates thereof wherein R ³ may be selected from hydrogen, C(i _-4) alkenyl, arylC ₍ i- ₄₎ alkyl groups. Within this subset, all other definitions are as originally defined' with respect to formula (I).

Particularly useful compounds may be selected from but not limited to; 2-[l -(3-Chloro-4-methoxy-benzenesulfonyl)-piperidin-3-yl]-N-moφ holin-4-yl- acetamide;

2-[l-(3-Chloro-4-fluoro-benzenesulfonyl)-piperidin-3-yl]- N-piperidin-l-yl-acetamide;

2-[l-(3-Chloro-4-fluoro-benzenesulfonyl)-piperidin-3-yl]- N-morpholin-4-yl-acetamide;

2-( 1 -Benzenesulfonyl-piperidin-3-yl)-iV-piperidin- 1 -yl-acetamide; 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- N-piperidin-1-yl acetamide;

2[ 1 -(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- N-morpholine-4-yl acetamide;

[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] -acetic acid N phenyl hydrazide; [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]aceticacid N-

(2,4dichlorophenyl)hydrazide;

[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]acetic acid N-benzyl hydrazide;

2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] N -pyrrolidine 1-yl acetamide; [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] acetic acid N'-cyclohexyl hydrazide;

2(1- benzenesulfonyl-piperidin-3-yl)- N-(4-methyl piperizin-l-yl)acetamide;

2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- N-(4-methyl piperizin-1- yl)ueetumidc;

[l-(4-Chloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid /V'-phenyl-hydrazide;

[l-(4-Chloro-benzenesulfonyl)-piperidin-3-yl]aceticacid λ''-(2,4-dichlorophenylphenyl) hydrazide;

N-azepan-l-yl-2-[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] acetamide; 2-(l- benzenesulfonyl-piperidin-3-yl)- N-(4-methyl piperidin-1-yl) acetamide;

[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]-acetic acid W(4-chloro phenyl) hydrazide;

[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]-acetic acid yV'(2-chloro phenyl) hydrazide; 1 - { 2- [ 1 -(3 -Chloro-2-methyl benzenesulfonyl)-piperidin-3 -yl] -acetylamino } -piperidin-

3-carboxylic acid, methyl ester;

2-(l- benzenesulfonyl)-piperidin-3-yl)- 7V-(3-methyl piperidinl-yl)acetamide;

2[l-(3-Chloro-2 -methyl benzenesulfonyl)-piperidin-3-yl]- 7V-(hexahydro cyclopentafc] pyrrole-2-yl)-acetamide; 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- _J /V-(4-methyl piperidinl- yl)acetamide;

1 -[2-(I - benzenesulfonyl-piperidin-S-yO-acetylaminoJ-piperidin-S-carb oxylic acid; l-[2-(l- benzenesulfonyl-piperidin-3-yl)-acetylamino]-piperidin-3-car boxylic acid amide; 2-(l- benzenesulfonyl)-piperidin-3-yl)- N-(2 -methyl piperidinl-yl)acetamide; 2-[l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl]-N-piperidin -l-yl-acetamide; 2-[l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl]-N-moφholin -4-yl-acetamide; ( 1 -Benzenesulfonyl-piperidin-3 -yl)-acetic acid ./V-(2,4-dichloro-phenyl)-hydrazide; [ 1 -(4-Methoxy-benzenesulfonyl)-piperidin-3 -yl] -acetic acid N-phenyl-hydrazide; [l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl]-acetic acid iV-cyclohexyl-hydrazide; 2-[ 1 -(4-Methoxy-benzenesulfonyl)-piperidin-3-yl]-N-pyrrolidin- 1 -yl-acetamide; [l-(4-Trifluoromethoxy-benzenesulfonyl)-piperidin-3-yl] -acetic acid iV-(2,4-dichloro- phenyl)-hydrazide;

N-Piperidin-l-yl-2-fl -(4-triflυoromethoxy-benzenesulfonyl)-piperidin-3-yl]-aceta mide; N-Morpholin-4-yl-2-[l-(4-trifluoromethoxy-benzenesulfonyl)-p iperidin-3-yl]- acetamide;

[l-(4-Trilluorυmethoxy-benzenesulfonyl)-piperidin-3-yl]- acetic acid iV-phenyl- hydrazide;

[l-(4-Trifluoromethoxy-benzenesulfonyl)-piperidin-3-yl]-a cetic acid W-cyclohexyl- hydrazide;

N-Pyrτolidin-l-yl-2-[l -(4-trifluoromethoxy-benzenesulfonyl)-piperidin-3-yl]- acetamide; [l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl] -acetic acid jY-(2,4-dichloro-phenyl)- hydrazide;

(l-Benzenesulfonyl-piperidin-3-yl)-acetic acid 7V-(2-chloro-phenyl)-hydrazide;

(1 -Benzenesulfonyl-piperidin-3-yl)-acetic acid 7V-(3-chloro-phenyl)-hydrazide;

(1 -Benzenesulfonyl-piperidin-3-yl)-acetic acid N'-(3-chloro-4-methyl-phenyl)- hydrazide;

1 - [2-( 1 -Benzenesulfonyl-piperidin-3-yl)-acetylamino] -piperidine-3 -carboxy lie acid, methyl ester;

2-[l-(3,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-pip eridin-l-yl-acetamide;

2-(l -Benzenesulfonyl-piperidin-3-yl)-iV-(4-phenyl-piperidin- 1 -yl)-acetamide; 2-( 1 -Benzenesulfonyl-piperidin-3 -yl)- 1 -piperidin- 1 -yl-ethanone;

2-(l-Benzenesulfonyl-piperidin-3-yl)-N-(4-benzyl-piperidi n-l-yl)-acetamide; 2-[l-(3-Chloro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-( 4-phenyl-piperidin-l-yl)- acetamide;

2-(l -Benzenesulfonyl-piperidin-3 -yl)-N-morpholin-4-yl-acetamide; 2-[l-(4-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-piperidin- l-yl-acetamide; 2-[l-(4-Chloro-benzenesulfonyl)-piperidin-3-yl]-iV-morpholin -4-yl-acetamide; ( 1 -Benzenesulfonyl-piperidin-3-yl)-acetic acid iV-phenyl-hydrazide; Adamantane- 1 -carboxylic acid iV-[2-( 1 -benzenesulfonyl-piperidin-3 -yl)-acetyl] - hydrazide; 4-Chloro-benzoic acid 7V-[2-(l-benzenesulfonyl-piperidin-3-yl)-acetyl]-hydrazide;

[l-(2-Fluoro-4-methoxy-benzenesulfonyl)-piperidin-3-yl]-a cetic acid 7V-(2,4-dichloro- phenyl)-hydrazide;

N- Azepan- 1 -yl-2-( 1 -benzenesulfonyl-piperidin-3 -yl)-acetamide; 2-( 1 -Benzenesulfonyl-piperidin-3 -yl)-N-(3 -hydroxymethy 1-piperidin- 1 -y l)-acetamide; ( 1 -Benzenesulfonyl-piperidin-3-yl)-acetic acid N'-(2,4-dimethyl-phenyl)-hydrazide; ( 1 -Benzenesulfonyl-piperidin-3 -yl)-acctic acid ^-(2,3 -dimcthyl-phcnyl)-hydrazide; N-Azcpan-l-yl-2-(l-bcnzcncsulfonyl-pipcridin-3-yl)-acetamide , Hydro chloride salt; 2-(l-Benzenesulfonyl-piperidin-3-yl)-N-(3-benzyloxymethyl-pi peridin-l-yl)- acetamide;

2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-jV-piperi din-l -yl-acetamide;

2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-morphol in-4-yl-acetamide;

[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid /V-phenyl-hydrazide;

2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-pyrroli din-l -yl-acetamide; [l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid /V-benzyl-hydrazide;

[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid yV-cyclohexyl-hydrazide;

[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid /V-(2,4-dichloro-phenyl)- hydrazide;

2-[l-(3-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-piperid in-l-yl-acetamide; 2-[l-(3-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-moφholin- 4-yl-acetamide;

[ 1 -(3 -Chloro-benzenesulfonyl)-piperidin-3-yl] -acetic acid jY-(2,4-dichloro-phenyl)- hydrazide;

2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-piperid in-l -yl-acetamide;

2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-λ ^L moφholin-4-yl-acetamide; [l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid 7V-(2,4-dichloro-phenyl)- hydrazide;

2-[l-(4-Fluoro-benzenesulfonyl)-piperidm-3-yl]-N-(4-methy l-piperazin-l-yl)- acetamide; vV-Azepan- 1 -yl-2-[ 1 -(4-fluoro-benzenesulfonyl)-piperidin-3-yl]-acetamide; 2-[ 1 -^S-Dichloro-benzenesulfonyO-piperidin-S-ylJ-iV-piperidin- 1 -yl-acetamide;

2-[l-(3,5-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-mor pholin-4-yl-acetamide;

2-( 1 -Benzenesulfonyl-piperidin-3 -yl)-N-(3 ,4-dihydro- 1 H-isoquinolin-2-yl)-acetamide;

2- [ 1 -(2-Chloro-benzenesulfonyl)-piperidin-3 -yl] -N-(4-methyl-piperidin- 1 -yl)- acetamide; N-Piperidin- 1 -yl-2-[ 1 -(toluene-2-sulfonyl)-piperidin-3 -yl] -acetamide;

λ ^L Moφholin-4-yl-2-[l-(toluene-2-sulfonyl)-piperidin-3-yl]-ace tamide;

N-Moφholin-4-yl-2- [ 1 -(naphthalene-2-sulfonyl)-piperidin-3 -yl] -acetamide;

2-[l-(νaphthalene-2-sulfonyl)-piperidin-3-yl]-N-piperidi n-l-yl-acetamide;

N-Azepan- 1 -yl-2-[ 1 -(naphthalene-2-sulfonyl)-piperidin-3-yl]-acetamide; N-(Hexahydro-cyclopenta[c]pyrrol-2-yl)-2-[ 1 -(naphthalene-2-sulfonyl)-piperidin-3-yl]- acetamide;

N-(3 -Methyl-piperidin- 1 -yl)-2- [ 1 -(naphthalene-2-sulfonyl)-piperidin-3 -yl] -acetamide- piperidin- 1 -yl-acetamide;

2- [ 1 -(Naphthalene- 1 -sulfonyl)-piperidin-3 -yl] -N-piperidin- 1 -yl-acetamide;

7V-Mθφholin-4-yl-2-[l-(naphthalene-l -sulfonyl)-piperidin-3-yl]-acetamide;

N-Azepan-l-yl-2-[l-(4-isopropyl-benzenesulfonyl)-piperidi n-3-yl]-acetamide;

N-(Hexahydro-cyclopenta[c]pyrrol-2-yl)-2-[l-(4-isopropyl- benzenesulfonyl)-piperidin-

3-yl]-acetamide; l-Benzenesulfonyl-piperidine-S-carboxylic acid azocan-1-ylamide;

2-[l -(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-piperidin- l-yl-acetamide;

2-[l-(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-mo� �holin-4-yl-acetamide;

2- [ 1 -(4-Isoprop yl-benzenesulfonyl)-piperidin-3 -yl] -N-(3 -methy 1-piperidin- 1 -y I)- acetamide; 2-[l-(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-(3-met hyl-piperidin-l-yl)- acetamide;

2-[l -(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-jV-(hexahydr o-cyclopenta

[c]pyrrol-2-yl)-acetamide;

N-Azepan-l-yl-2-[l-(2,4-dichloro-benzenesulfonyl)-piperid in-3-yl]-acetamide; N-Moφholin-4-yl-2-[l-(2,4,6-trimethyl-benzenesulfonyl)-pipe ridin-3-yl]-acetamide; N-Piperidin- 1 -yl-2-[ 1 -(2,4,6-trimethyl-benzenesulfonyl)-piperidin-3-yl]-acetamide ;

(1 -Benzenesulfonyl-piperidin-3-yl)-acetic acid iV-benzyl-hydrazide;

[1 -(Toluene-4-sulfonyl)-piperidin-3-yl]-acetic acid jV-phenyl-hydrazide;

[1 -(Toluene-4-sulfonyl)-piperidin-3-yl]-acetic acid 7V-(2,4-dichloro-phenyl)-hydrazide; N-Piperidin- 1 -yl-2-[l -(toluene-4-sulfonyl)-piperidin-3-yl]-acetamide; N-Pyrrolidin- 1 -yl-2-[ 1 -(toluene-4-sulfonyl)-piperidin-3-yl]-acetamide; [ 1 -(Toluene-4-sulfonyl)-piperidin-3-yl]-acetic acid iV-cyclohexyl-hydrazide; ( 1 -Benzenesulfonyl-piperidin-3-yl)-acetic acid N'-(4-chloro-phenyl)-hydrazide; ( 1 -Benzenesulfonyl-piperidin-3 -yl)-acetic acid iV-tert-butyl-hydrazide; (1 -Ben7.enesulfonyl-piperidin-3-yl)-acetic acid N-butyl-hydrazide;

2-(l-Benzenesulfonyl-piperidin-3-yl)-iV-(hexahydro-cyclop enta[c]pyrrol-2-yl)- acetamide;

[l-(3-Chloro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-ac etic acid jV-tert-butyl- hydrazide; [1 -(3-Chloro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-acetic acid N-butyl-hydrazide; 2- [ 1 -(4-Isopropyl-benzenesulfonyl)-piperidin-3-yl] -N-piperidin- 1 -yl-acetamide; 2-[l-(4-Isopropyl-benzenesulfonyl)-piperidin-3-yl]-iV-moφho lin-4-yl-acetamide; (1 -Benzenesulfonyl-piperidin-3 -yl)-acetic acid N'-(3-nitro-phenyl)-hydrazide; yV-A7,epan-1 -yl-2-[l -(4-fluoro-ben7.enesiilfonyl)-piperidin-3-yl]-λcetamide;

r

2-[ 1 -(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-(hexahydro-cyc lopenta [c] pyrrol-

2-yl)-acetamide;

2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-(4-meth yl-piperidin-l-yl)- acetamide; 2-[l -(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-(3-methyl-pipe ridin- 1 -yl)- acetamide;

2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-λ'-p iperidin-l-yl-acetamide;

2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-iV-mo φholin-4-yl-acetamide;

[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid 7V-(2,4-dichloro-phenyl)- hydrazide;

2-[ 1 -(2,5-Dichloro-benzenesulfonyl)-piperidin-3-yl]-iV-piperidin - 1 -yl-acetamide;

2-[l-(2,5-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-mo� �holin-4-yl-acetamide; iV-Piperidin-l-yl-2-[l-(2,4,6-trichloro-benzenesulfonyl)-pip eridin-3-yl]-acetamide;

λ ⁷ -Mθφholin-4-yl-2-[l-(2,4,6-trichloro-benzenesulfonyl)-pipe ridin-3-yl]-acetaniide; N-Azepan-l-yl-2-[l-(2,3-dichloro-benzenesulfonyl)-piperidin- 3-yl]-acetamide;

2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-jV-(o ctahydro-pentalen-2-yl)- acetamide;

2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-(4- methyl-piperidin-l-yl)- acetamide; 2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-(3-met hyl-piperidin-l-yl)- acetamide;

[ 1 -(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid iV-(2-chloro-phenyl)- hydrazide;

[ 1 -(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid iV-(4-chloro-phenyl)- hydrazide;

2-[l-(3-Chloro-4-methyl-benzenesulfonyl)-piperidin-3-yl]- N-piperidin-l-yl-acctamidc;

2- [ 1 -(3 -Chloro-4-methyl-benzenesulfonyl)-piperidin-3 -yl] -N-morpholin-4-y 1- ₍ acetamide;

2-[l -(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-(hexahydro-cyc lopenta [c] pyrrol-2- yl)-acetamide;

[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid 7V-(2-chloro-phenyl)- hydrazide;

[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid N'-(4-chloro-phenyl)- hydrazidc;

2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-(3-meth yl-piperidin-l-yl)- acetamide;

2-[ 1 -(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-jY-piperidin - 1 -yl-acetamide;

2-[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-mo� �holin-4-yl- acetamide;

2-[l-(4-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]- N-piperidin-l -yl-acet amide;

2-[l-(4-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]- N-moφholin-4-yl- acetamide;

2-[l-(2,6-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-pip eridin-l-yl-acetamide; 2-[l-(2,6-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-moφho lin-4-yl-acetamide;

N-Azepan-l-yl-2-[l-(2,4-difluoro-benzenesulfonyl)-piperid in-3-yl]-acetamide;

2-[ 1 -(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-(hexahydro -cyclopenta [c] pyrrol-2-yl)-acetamide;

2-[ 1 -(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-(3-methyl- piperidin- 1 -yl)- acetamide;

[1 -(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid iV-(2-chloro-phenyl)- hydrazide;

[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid 7V-(4-chloro-phenyl)- hydrazide; 2-[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-7V-(4-me thyl-piperidin-l-yl)- acetamide; iV-azepan-l-yl-2-[l-(3,4-dichloro-benzenesulfonyl)-piperidin -3-yl] acetamide;

2[l-(2,3-dichloro- benzenesulfonyl)-piperidin-3-yl]- N-(hexahydro cyclopenta[c] pyrrole-2-yl)-acetamide; 2[l-(2,3-dichloro benzenesulfonyl)-piperidin-3-yl]- N-(3-methyl piperidinl- yl)acetamide;

2[l-(2,3-dichloro benzenesulfonyl)-piperidin-3-yl]- N-(4-methyl piperidinl- yl)acetamide;

[l-(3,4-dichloro-benzenesulfonyl)-piperidin-3-yl]aceticacid phenyl) hydrazide;

[1 -(3,4-dichloro-benzenesulfonyl)-piperidin-3-yl]aceticacid iV-(2-chlorophenyl phenyl) hydrazide;

1 - { 2 [ 1 -(2,3 -dichloro benzenesulfonyl)-piperidin-3 -yl] -acetylamino } -piperidin-3 - carboxylic acid, methyl ester;

N-Azepan-l-yl-2-[l-(2-chloro-benzenesulfonyl)-piperidin-3 -yl]-acetamide;

2-[l-(4-Chloro-2-fluoro-benzenesulfonyl)-piperidin-3-yl]- λ/-piperidin-l -yl-acetamide;

2-[l-(4-Chloro-2-fluoro-benzenesulfonyl)-piperidin-3-yl]- N-moφholin-4-yl-acetamide;

2-[l-(2-Chloro-4-fluoro-benzenesulfonyl)-piperidin-3-yl]- 7V-piperidin-l -yl-acetamide; 2-[l-(2-Chloro-4-fluoro-benzenesulfonyl)-piperidin-3-yl]-jV- moφholin-4-yl-acetamide;

2-[l-(4-Amino-benzenesulfonyl)-piperidin-3-yl]-N-piperidi n-l-yl-acetamide;

2-[l-(4-Acetylamino-benzenesulfonyl)-piperidin-3-yl]-N-pi peridin-l -yl-acetamide;

2-[l-(3-Chloro-4-methoxy-benzenesulfonyl)-piperidin-3-yl]-λ ^L piperidin-l -yl- acetamide; 2-[ 1 -(5-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-piper idin- 1 -yl-acetamide;

2-[l-(5-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]- N-moφholin-4-yl- acetamide;

2-[ 1 -(2,5-Dichloro-thiophene-3-sulfonyl)-piperidin-3-yl]-N-piper idin- 1 -yl-acetamide;

2-[l-(2,5-Dichloro-thiophene-3-sulfonyl)-piperidin-3-yl]- 7V-moφholin-4-yl-acetamide; 2-[l-(2-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-piperidin- l-yl-acetamide;

2-[l-(2-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-moφhol in-4-yl-acetamide;

2-[l -(2-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-(hexahydro-cyc lopenta[c] pyrrol -2- yl)-acetamide;

2-[l-(2-Fluoro-5-methyl-benzenesulfonyl)-piperidin-3-yl]- N-piperidin-l -yl-acetamide; 2-[ 1 -(2-Fluoro-5-methyl-benzenesulfonyl)-piperidin-3-yl]-λ'-mo� �holin-4-yl- acetamide;

2-[l-(3-Fluoro-4-methyl-benzenesulfonyl)-piperidin-3-yl]- iV-(3-methyl-piperidin-l-yl)- acetamide;

2-[ 1 -(3-Fluoro-4-methyl-benzenesulfonyl)-piperidin-3-yl]-iV-pipe ridin- 1 -yl-acetamide; 2-[l-(3 -Fluoro-4-methy l-benzenesulfonyl)-piperidin-3 -yl] -iV-moφholin-4-y 1- acetamide;

[1 -(4-Mtro-benzenesulfonyl)-piperidin-3-yl] -acetic acid λ/'-(2,4-dichloro-phenyl)- hydrazide;

N-Moφholin-4-yl-2-[l-(4-nitro-benzenesulfonyl)-piperidin -3-yl]-acetamide; 2-[l-(4-Nitro-benzenesulfonyl)-piperidin-3-yl]-N-piperidin-l -yl-acetamide; 2-(l-Benzenesulfonyl-piperidin-3-yl)-N-methyl-iV-piperidin-l -yl-acetamide; 2-( 1 -Benzenesulfonyl-piperidin-3 -yl)-N-methy l-N-(3 -methyl-piperidin- 1 -yl)-acetamide; 2-[l-(3-Chloro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-m ethyl-iV-piperidin-l-yl- acetamide;

2-(l-Benzenesulfonyl-piperidin-3-yl)-N-ethyl-N-piperidin- l-yl-acetamide;

N-Methyl-2-[l-(4-nitro-benzenesulfonyl)'piperidin-3-yl]-N -piperidin-l-yl-acetamide;

N-Azepan-l -yl-2-[l-(2-chloro-benzenesulfonyl)-piperidin-3-yl]-N-methyl -acetamidc;

2-(l-Benzenesulfonyl-piperidin-3-yl)-N-(hexahydro-cyclope nta[c]pyrrol-2-yl)-jV- methyl-acetamide;

N-Azepan-l-yl-2-[l-(4-fluoro-benzenesulfonyl)-piperidin-3 -yl]-N-methyl-acetamide;

2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-jV-(hexah ydro-cyclopenta[c] pyrrol-2- yl)- jV-methyl-acetamide;

2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-methyl- N-(3-methyl-piper idin-1 - yl)-acetamide;

2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-met hyl-N-morpholin-4-yl- acetamide;

2-(l-Benzenesulfonyl-piperidin-3-yl)-N-niethyl-N-moφholi n-4-yl-acetamide;

N-Azepan-l-yl-2-(l-benzenesulfonyl-piperidin-3-yl)-N-methyl- acetamide; _> or a pharmaceutically acceptable salt of any of the compounds above.

The novel compounds of the present invention may be prepared using the reactions and techniques described below, together with conventional techniques known to those skilled in the art of organic synthesis, or variations thereon as appreciated by those skilled in the art. The reactions are performed in solvents appropriate to the reagents and materials employed and are suitable for the transformations being effected. Preferred methods include, but not limited to those described below, where all symbols are as defined earlier unless and otherwise defined below.

List of abbreviations used in the description of the preparation of the compounds of the present invention: bs: broad singlet nBuLi: n-butyl lithium

CDCl ₃ : Deuterated chloroform

CHCl ₃ : Chloroform d: doublet dd: doublet of doublet dt: doublet of triplet

DCM: Dichloromethane

DMAP: 4-(Dimethylamino) pyridine

DMF: N,7V-Dimethyl formamide

DMSO: Dimethyl sulfoxide

EDCI: iV-(3-Dimethylaniinopropyl)-7V-ethylcarbodiimide

Et ₃ N: Triethyl amine EtOAc: Ethyl acetate

EtOH: Ethanol g: gram

HCl(g): Hydrogen chloride (gas)

HOBT: 1 -Hydroxybenzotriazole K ₂ CO ₃ : Potassium carbonate

KI: Potassium iodide

KOH: Potassium hydroxide

LiAlH ₄ : Lithium Aluminum Hydride

LiHMDS: Lithium bis(trimethylsilyl)amide MeOH: Methanol m: multiplet mmol: millimoles mol: moles mL: milliliter MsCl: Methane sulfonyl chloride

MS: Mass spectrum

NaCN: Sodium cyanide

NaH: Sodium hydride

IH NMR: Proton nuclear magnetic resonance Pet ether: Petroleum ether, boiling range (60-80 ⁰ C) s: singlet

SOCl ₂ : Thionyl chloride t: Triplet td: triplet of doublet THF: Tetrahydrofuran

TLC: Thin layer chromatography

The compounds of the formula I_may be prepared as described in scheme 1:

Scheme A:

Ia

The compound (II), the common intermediate for all the compounds of interest, was coupled with various hydrazines by using EDCI and DMAP in chlorinated solvents, most preferably dichloromethane to furnish the compounds of the formula (Ia). The compound (II) was synthesized by following three schemes.

Scheme 1:

(±)-Nipecotic acid (2) was coupled with substituted benzene sulfonyl chloride (3) by using suitable bases, such as sodium carbonate, potassium carbonate, triethyl amine, sodium hydride in suitable solvent(s), preferably water or DCM to yield the acid (4). Acid (4) was esterified by using thionyl chloride in alcoholic solvent(s) such as methanol, ethanol, propanol, butanol and the like, 1 -propanol being preferred, at temperature ranging from room temperature to reflux to yield (5). The ester (5) was reduced by using various reducing agents known in the art, lithium aluminum hydride being preferred, in ethereal solvents like THF to furnish alcohol (6). Alcohol (6) was converted into the corresponding mesylate derivative by treating the alcohol (6) with methane sulfonyl chloride in suitable chlorinated solvents, DCM being preferred at room temperature. The corresponding mesylate derivative was subjected to nucleophilic substitution reaction by using sodium cyanide in suitable solvents like DMF, THF, DMSO and the like to get the nitrile derivative (7). The nitrile (7) was converted to ester (8) by reacting it with hydrochloride gas in suitable alcoholic solvents, preferred being methanol, ethanol, 1-propanol. The ester (8) was hydrolyzed under basic conditions to yield the acid (II).

Scheme 2:

OH C OHn ₂₂ CVyII ₂₂

H

(±)Piperidine-3 -methanol (9) was coupled with substituted benzenesulfonyl chloride (3) in suitable solvent(s) most preferred being DCM, THF using suitable bases including triethyl amine, sodium hydride, nBuLi, LiHMDS to get alcohol (6). Alcohol (6) was converted into corresponding mesylate derivative by treating the alcohol with

methane sulfonyl chloride in suitable chlorinated solvents, DCM being preferred at room temperature. The corresponding mesylate derivative was subjected to nucleophilic substitution reaction by portion wise addition of sodium cyanide in suitable solvent(s) like DMF, THF, DMSO to get the corresponding nitrile derivative (7). The nitrile (7) was converted to ester (8) by reacting it with hydrochloride gas in suitable alcoholic solvent(s), preferred being methanol, ethanol, 1-propanol. The ester (8) was hydrolyzed under basic conditions to yield the acid (II). Scheme 3:

_h rf ^ϊ_ _(R 5 _)n

10

NaCN, DMF, 6O ⁰ C

7 8 „ (±)Piperidine-3 -methanol (9) was coupled with substituted benzenesulfonyl chloride (3) in suitable solvent(s) most preferred being DCM, THF using suitable bases including triethyl amine, sodium hydride, nBuLi, LiHMDS to get alcohol (6). Alcohol (6) was converted into the mesylate derivative by treating the alcohol with methane sulfonyl chloride in suitable chlorinated solvent(s), DCM being preferred at room temperature. The mesylate derivative was subjected to iodination by suitable iodinating agents like sodium iodide or potassium iodide in suitable solvents like THF, DMF to yield corresponding iodide (10). The iodide (10) was subjected to the nucleophilic substitution reaction by portion wise addition of sodium cyanide in suitable solvent(s) like DMF, THF, DMSO to get corresponding nitrile derivative (7). The nitrile (7) was converted to ester (8) by reacting it with hydrochloride gas in suitable alcoholic solvents, preferred being methanol, ethanol, 1-propanol. The ester (8) was hydrolyzed under basic conditions to yield the acid (II). Scheme B: /V-alkylation

Ia Ib

The compound (Ia) was treated with suitable alkyl/cycloalkyl halides with suitable base(s), preferred being NaH, nBuLi in suitable solvent(s) like THF at the temperature ranging from -78 ⁰ C to O ⁰ C to yield the compound (Ib). Scheme 4: Resolution of the intermediate acid:

Preparation of (+)-l-benzenesulfonyl piperidine-3-carboxylic acid

Ia

(±)-l-benzenesulfonyl piperidine-3-carboxylic acid was resolved by preparing its chiral salt with (S)-(-)-α-mcthyl benzyl amine or (R)-(+)-α-methyl benzyl amine, followed by recrystallization in ethanol and finally hydrolysis of these salts with HCl gave corresponding (+) and (-) 1-benzenesulfonyl piperidine-3-carboxylic acid. Procedure:

(a) (±)-l-benzenesulfonyl piperidine-3-carboxylic acid (15g, 55.76 mmole) was dissolved in acetone (30OmL), stirred and (S)-(-)-α-methyl benzyl amine (7.1 niL, 55.76 mmole) was added and resulting white solid was stirred for additional 30 min. White solid salt was filtered in vacuo and reslurried with acetone (200 mL) and filtered again and dried in vacuo, to obtain chiral salt (16.4g). From this salt (12g) was mixed with absolute ethanol (200 mL) and refluxed till complete dissolution, it was allowed to cool to room temperature, and white crystalline needles were filtered and dried under reduced pressure to obtain crystalline salt (9.8 g). This crystalline salt was then mixed with water and acidified with 10% HCl (1OmL, pH =3-4), extracted with chloroform. Organic layer was washed with water, brine and dried over sodium sulfate, concentrated under reduced pressure to obtain 1 -benzenesulfonyl piperidine-3- carboxylic acid (6.7g, 24.90 mmole). 1 -benzenesulfonyl piperidine-3-carboxylic acid thus obtained, was dissolved in acetone, stirred and (S)-(-)-α-methyl benzyl amine (3.17mL, 24.90 mmoles) was added and resulting white solid was stirred for additional 30 min. and filtered to obtain salt (7.5 g). The salt was mixed with absolute ethanol and refluxed till complete dissolution, it was allowed to cool to room temperature, and white crystalline needles were filtered and dried under reduced pressure to obtain crystalline salt (5.5g). Again it was recrystallized following the same procedure twice to obtain the salt (3.3 g) with chiral purity 97.84% (by chiral HPLC). This crystalline salt was then mixed with water and acidified with 10% HCl (3mL, pH =3-4), extracted with chloroform. Organic layer was washed with water, brine and dried over sodium sulfate, concentrated under reduced pressure to obtain (+)-l -benzenesulfonyl piperidine-3-carboxylic acid (2.25g). Chiral purity: 97.68 % (by chiral HPLC). Scheme 5: Resolution of the intermediate acid

Preparation of (-)-l-benzenesulfonyl piperidine-3-carboxylic acid

0 ₍ ^-\ ,λ^

_{SOC 21 M} e _O H O ^A ° ^Me L ₁ AIH. THF Q "" ^{1 E} t ₃ ^N, Ms ^CI . ^CH ^ IJ » ^■ N »- O=S=O ° ° ^{c t0 reflux} O-S-O

O "C to reflux _O =S=O O °C to rt ^" l 2 NaCN. DMF. 60 ⁰ C

-(R ⁵ )n -<R°)n

(R ⁵ )π

22

20 21

Ia

(-)-l-benzenesulfonyl piperidine-3-carboxylic acid was obtained by using (R)-

(+)-α-methyl benzyl amine and following the similar process with chiral purity: 96.67 % (by chiral HPLC).

The invention including processes for preparing the compounds of the invention are further exemplified by the following non-limiting examples which are representative in nature and are not meant to limit the scope of the invention in any way. The following compounds were prepared according to the general Scheme 1 described above.

IH NMR spectral data given in the examples (vide infra) are recorded using either a

300 MHz or a 400 MHz spectrometer and reported in δ scale. Until and otherwise mentioned the solvent used for NMR is CDCI ₃ using tetramethyl silane as the internal standard.

The following examples were prepared according to the general scheme 1 above.

Example 1.1

2-( 1 -Benzenesulfonyl-piperidin-S-yty-N-piperidin- 1 -yl-acetamide

Step A: l-Benzenesulfonyl-piperfdineS-carboxylic acid Nipecotic acid (25 g, 193.79 mmol, 1 equiv.) was taken in a round bottomed flask. To this, sodium carbonate (61.62 g, 581.3 mmol, 3 equiv.) and water (250 mL)

were added. The solution was kept in an ice bath and stirred for 10 minutes. To this solution, benzenesulfonyl chloride (41.04 g, 29.8 mL, 232.54 mmol, 1.2 equiv.) was added at 0 ⁰ C to 5 ⁰ C. After addition, the reaction mixture was stirred at room temperature for 16h. After overnight stirring, TLC was checked for completion of the reaction. The reaction mixture was diluted with water (200 mL) and washed with ethyl acetate. The aqueous layer was collected and acidified with dil HCl upto pH 3 at 0 ⁰ C to 5 ⁰ C, and was stirred for 15-30 minutes. White solid was obtained, which was filtered, washed with petroleum ether and dried in air and then in vacuo till constant weight to furnish the desired compound. (5 Ig, 97.83%). IH NMR (CDCl ₃ , 400 MHz): δ 7.77 (d, J= 8 Hz, 2H); 7.63-7.52 (m, 3H); 3.83 (dd, J = 2.8, 8.8 Hz, IH); 3.60 (d, J = 11.6 Hz, IH); 2.71-2.64 (m, IH); 2.57 (t, J = 1 1.2 Hz, IH); 2.40 (dt, J = 2.8 Hz, 10.8 Hz, IH); 2.03-1.99 (m, IH); 1.84-1.79 (IH, m); 1.72- 1.61 (IH, m); 1.47-1.46 (IH, m).

Step B: l-Benzenesulfonyl-piperidine-3-carboxylic acid, methyl ester The acid (51 g, 189.5 mmol, 1 equiv.) from above, was dissolved in dry methanol

(500 mL) in a round bottomed flask. Thionyl chloride (32.39 g, 19.75 mL, 284.25 mmol, 1.5 equiv.) was added dropwise into the reaction mixture at 0 ⁰ C to 5 ⁰ C. After the addition, the reaction mixture was brought to room temperature and then refluxed. The reaction was monitored by TLC till completion. The methanol was evaporated from the reaction mixture to obtain oily liquid. It was dissolved in ethyl acetate (400 mL) and washed with water followed by brine and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to furnish the desired ester (5 Ig, 95.14%). IH NMR (CDCl ₃ , 400 MHz): δ 7.77 (d, J= 8 Hz, 2H,); 7.63-7.52 (m, 3H); 3.83 (dd, J = 2.8, 8.8 Hz, IH); 3.68 (s, 3H); 3.60 (d, J= 11.6 Hz, IH); 2.67-2.62 (m, IH); 2.51 (t, J = 11.2 Hz, IH); 2.36 (dt, J= 2.8, 10.8 Hz, IH); 2.04-1.96 (m, IH); 1.82-1.77 (IH, m); 1.69-1.64 (III, m); 1.51-1.36 (III, m). Step C: (l-Benzenesulfonyl-piperidin-3-yl) -methanol

The methyl ester (51 g, 180.2 mmol, 1 equiv.) from above, was dissolved in dry THF (500 mL) and transferred into pressure equalizing funnel. Lithium aluminum hydride (8.2 Ig, 216.2 mmol, 1.2 equiv.) was suspended in dry THF (100 mL) in a round bottomed flask (1 L). The ester from dropping funnel was added dropwise at 0 ⁰ C to 5 ⁰ C. After the complete addition, the reaction mixture was brought to room temperature and stirred. The reaction was monitored by TLC till completion. The

reaction mixture was cooled to 0 ⁰ C and carefully quenched with slow addition of aqueous KOH (IN). Gray colored free flowing solid was separated; ethyl acetate (500 mL) was added and then solid was filtered through hyflour using sintered disk. The filtrate was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to furnish the title compound (42g, 91.4%).

IH NMR (CDCl ₃ , 400 MHz): δ 7.77 (d, J= 8 Hz, 2H); 7.62-7.52 (m, 3H); 3.65 (dd, J = 2.8, 11.2 Hz, IH); 3.59-3.49 (m, 3H); 2.46 (t, J = 10.8 Hz, IH); 2.30 (t, J = 10.4 Hz, IH); 1.93-1.63 (m, 5H); 01.14-0.94 (m, IH). Step D: (]-Benzenesulfonyl-piperidin-3-yl)-acetonitrile The alcohol (42g, 164.7 mmol, 1 equiv.) from above, was dissolved in dry

.dichloromethane (420 mL) in a round-bottomed flask equipped with anhydrous CaCl ₂ guard tube. Triethylamine (19.16 g, 26.6 mL, 189.4 mmol, 1.15 equiv.) was added dropwise into the reaction mixture at 0-5 ⁰ C. After 10-20 minutes, methanesulfonyl chloride (28.28 g, 19.25 mL, 247 mmol, 1.5 equiv.) was added dropwise to the reaction mixture at the same temperature and stirred for 20-30 minutes and the reaction mixture was stirred to room temperature. The reaction was monitored by TLC till completion of reaction. The reaction mixture was diluted with dichloromethane (500 mL) and water (250 mL). The phases were separated and the organic layer dried with anhydrous sodium sulfate, filtered and concentrated in vacuo to furnish the desired mesylate derivative (54 g, 98.46%, yellow solid. The mesyalte derivative was used in next step without purification.

The mesylate (54g, 164.1 mmol, 1 equiv.) was dissolved in dry dimethyl formamide (250 mL) in round bottomed flask equipped with the air condenser and calcium chloride guard tube. 18-Crown-6 crown ether (1.080 g) was added in the reaction mixture followed by NaCN (20. Ig, 410.25 mmol, 2.5 equiv.). The reaction mixture then stirred for 14- 16h at 60 ⁰ C. TLC was checked for completion of the reaction when ice cold water was added into the reaction mixture. It was extracted with ethyl acetate. The combined organic layers were collected and washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the titled compound (4 Ig, 95.79%).

Ill NMR (CDCl ₃ , 400 MHz): 6 7.77 (d, J = 8 Hz, 211); 7.65-7.53 (m, 311); 3.56 (dd, J = 2.4, 11.6 Hz, IH); 3.52-3.49 (IH, m); 2.54-2.51 (IH, m); 2.48-2.33 (3H, m); 2.11-2.05 (IH, m); 1.85-1.76 (2H, m); 1.72-1.66 (IH, m); 1.24-1.19 (IH, m).

Step E: (l-Benzenesulfonyl-piperidin-3-yl) -acetic acid, methyl ester

The cyano derivative (48g, 181.1 mmol, 1 equiv.) from earlier step, was dissolved in dry methanol (500 mL) in a three necked round bottomed flask (1 L) equipped with condenser fitted with CaCl ₂ guard tube, and a gas inlet. HCl gas was passed through the reaction mixture. The reaction was monitored by TLC using EtOAc:Pet Ether ( 1 : 1 ) as a mobile phase. After completion of the reaction, air was passed through the reaction mixture to remove the excess HCl gas and then methanol was remove in vacuo. The residue was dissolved in ethyl acetate (500 mL) and water (100 mL) was added. Organic layer was separated and washed with water (2 X 100 mL), brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to furnish the ester (52.5g, 97.22%, white solid). MP: 70-72 ⁰ C. MoI Formula: C ₁₄ H ₁₉ NO ₄ S. MS: 298 (M + H) ⁺ , 320 (M + Na) ⁺ ; IH NMR (CDCl ₃ , 400 MHz): δ 7.77 (d, J= 8 Hz, 2H); 7.65- 7.53 (m, 3H); 3.68 (s, 3H); 3.56-3.48 (m, 2H); 2.49-2.31 (m, IH); 2.29-2.04 (m, 3H); 1.74-1.66 (m, 2H), 1.64-1.58 (m, 2H); 1.14-0.94 (m, IH). Step F: (l-Benzenesulfonyl-piperidin-3-yl) -acetic acid

The ester (44.4g, 151.5mmol, 1 equiv.) as obtained above, was dissolved in methanol (440 mL) in a round bottomed flask. Potassium hydroxide (25.45g, 454.5 mmol, 3 equiv.) in water was added slowly in the reaction mixture. The reaction mixture was stirred at room temperature for 16-18h. The completion of the reaction was confirmed by TLC. The methanol was removed in vacuo and then diluted with water and acidified with HCl (2N) at 0 ⁰ C to 5 ⁰ C to obtain white solid. The solid was filtered through buckner funnel and washed with petroleum ether, dried in air and then in vacuo to constant weight (4Ig ₃ 96%). IH NMR (CDCl ₃ , 400 MHz): δ 7.77 (d, J= 8 Hz, 2H); 7.65-7.53 (m, 3H); 3.58 (d, J = 8 Hz, IH); 3.49 (d, J= 12 Hz, IH); 2.52 (t, J= 11.6 Hz, IH); 2.38-2.32 (IH, m); 2.29- 2.20 (2H, m). 2.19-2.16 (IH, m); 1.79-1.75 (2H, m); 1.73-1.63 (2H, m); 1.14-1.04 (IH, m). Step G: 2 -(I -Benzenesulfonyl-piperidin-3-yl) -N-piperidin- 1 -yl-acetamide

To a mixture of the acid (5 g, 17.66 mmol, 1 equiv., obtained above) and DMAP (2.15 g, 17.66 mmol, 1 equiv.), dry dichloromethane (50 mL) in a round bottomed flask was added EDCI (6.76g, 35.3 mmol, 2 equiv.) under nitrogen atmosphere, followed by 1-aminopiperidine (1.94 g, 19.42 mmol, 1.1 equiv.) at 0 ⁰ C to 5 ⁰ C. The reaction mixture was brought to the room temperature and stirred for 16h. The completion of the

reaction was checked by TLC. Then the reaction mixture was diluted with dichloromethane. The organic layer washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The compound was purified by column chromatography using (0.7:99.3) methanol xhloro form as eluent to furnish the desired product (4.2g, 65.4%).

IH NMR (CDCl ₃ , 300MHz) δ 7.71-7.77 (m, 2H), 7.50-7.62 (m, 3H), 3.45-3.50 (m,

IH), 2.92-3.20 (m, 3H), 2.7-2.77 (m, 2H), 2.01-2.43 (m, 4H), 2.45-2.55 (m, I H), 1.62-

1.76 (m, 7H), 1.25-1.41 (m, 2H), 1.05-1.15 (m, IH). .

The following compounds were prepared in a similar way as described in example 1.1 with suitable variations as is within the scope of a person skilled in the art.

Ex 1.2: 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- 7V-piperidin-l -yl acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.89-7.78 (m, IH); 7.57 (d, J- 7.98 Hz, IH); 7.25-7.22

(m, IH); 6.05 (s, IH); 3.54-3.50 (m, IH); 3.21-2.96 (m, 2H); 2.82-2.73 (m, 2H); 2.67 (s, 3H); 2.62-2.37 (m, 2H); 2.35-2.30 (m, 2H), 2.26-2.22 (m, 2H); 1.71-1.67(m, 6H);

1.40-1.16 (m, 4H); 0.85-0.75 (m, IH).

Ex 1.3: 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- N-morpholine-4-yl acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.88-7.76 (m, IH); 7.58 (d, J= 7.9 Hz, IH); 7.26-7.22 (m, IH); 6.14 (s, IH); 3.84-3.81 (m, 3H); 3.50-3.48 (m, 2H); 3.26-3.22 (m, 2H); 2.9-

2.83 (m, 3H); 2.66 (s, 3H); 2.62-2.61 (m, IH); 2.42(d, J = 7 Hz, IH); 2.32-2.28 (m,

IH); 2.05-2.04(m, IH); 1.78-1.73 (m, 2H); 1.42-1.46 (m, IH); 1.25-1.20 (m, IH); 0.85-

0.75 (m, IH).

Ex 1.4: [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]-acetic acid N ¹ phenyl hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.81 (t, J = 8.37 Hz, IH); 7.57 (d, J = 7.7 Hz, 2H);

7.26-7.20 (m, 2H); 6.94-6.76 (m, 3H); 6.15-6.14 (m, IH); 5.94 (s, IH); 3.40-3.26 (m, 3H); 2.96-2.92 (m, IH); 2.65 (s, 3H); 2.43-2.39 (m, IH); 2.25-2.14 (m, 2H); 1.82-

1.74(m, 2H); 1.37-1.33(m, IH). Ex 1.5: [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]aceticacid N- (2,4dichlorophenyl)hydrazide

IH νMR: (CDCl ₃ , 300 MHz) δ 7.78 (d, J- 7.9 Hz, IH); 7.60-7.57 (m, 2H); 7.33-7.22 (m, 2H); 7.14-7.11 (m, IH); 6.87-6.79 (m, IH); 6.42 (d, J= 3.0 Hz ,1H); 3.34-3.23 (m,

3H); 3.06-3.00 (m, IH); 2.65 (s, 3H); 2.54-2.47 (m, I H); 2.27 -2.15 (m, 2H); 1.81 -1.78

(m, 2H); 1.43-1.39 (m, IH).

Ex 1.6: [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]acetic acid TV'-benzyl hydrazide IH NMR: (CDCh, 300 MHz) δ 12.12 (s, IH); 10.31 (s, I H); 7.80-7.73 (m, 3H); 7.45-

7.39 (m, 2H); 7.32-7.26 (m, 2H); 7.20-7.18 (m, IH); 3.58-3.36 (m, 3H); 2.73-2.68 (m,

IH); 2.66 (s, 3H); 2.48-2.44 (m, 2H); 2.21-2.10 (m, 2H); 2.08-2.03 (m, IH); 1.97-

1.85(m, 2H); 1.36-1.51(m, IH); 0.91-1.12(m, IH).

Ex 1.7: 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] iV'-pyrrolidinel-yl acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.88-7.80 (m, IH); 7.78-7.58 (m, IH); 7.56-7.24 (m,

IH); 6.0 (s, IH); 3.26-3.22 (m, 2H); 3.21-2.96 (m, IH); 2.94-2.85 (m, 3H); 2.66 (s, 3H); 2.68-2.59 (m, IH); 2.59-2.35 (m, 2H); 1.86-1.83(m, 7H); 1.76-1.72(m, 2H); 1.17-

1.14(m, IH). Ex 1.8: [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]acetic acid N'- cyclohexyl hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.88-7.80 (m, IH); 7.57 (d, J= 7.8 Hz, IH), 7.26-7.21 (m, IH); 7.12(bs, IH); 3.38-3.37 (m, IH); 3.05-2.78 (m, 2H); 2.67 (s, 3H); 2.65-2.22 (m, 2H); 2.06-2.01 (m, IH); 1.84-1.72 (m, 7H); 1.60-1.57 (m, 2H); 1.29-1.08 (m, 7H). Ex 1.9: 2( 1 - benzenesulfonyl-piperidin-3-yl)- N-(4-methyl piperizin- 1 -yl)acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.77-7.72 (m, 2H); 7.61-7.57 (m, IH); 7.54-7.51 (m, 2H); 6.10 (s, IH); 3.48-3.38 (m, IH); 3.05-2.88 (m, 3H); 2.83-2.76 (m, 2H); 2.60- 2.57(m, IH); 2.51-2.49 (m, 3H); 2.31 (s, 3H); 2.28-2.19 (m, 3H); 2.04-2.00 (m, IH); 1.82-1.72 (m, 3H); 1.66-1.64(m, IH); 1.4-1.2(m, IH). Ex 1.10: 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- N-(4-methyl piperizin- 1 -yl)acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.89-7.78 (m, IH); 7.59-7.57 (m, IH); 7.26-7..24 (m, IH); 6.07 (s, IH); 3.56-3.48 (m, 2H); 3.22-3.21 (m, IH); 2.97-2.94 (m, IH); 2.88-2.84 (m, 2H); 2.77-2.66 (m, 3H); 2.63 (s, 3H); 2.62-2.47 (m, 3H); 2.42-2.38 (m, IH); 2.31 (s, 3H); 2.10-2.05 (m, IH); 1.76-1.73 (m, 2H); 1.65-1.54 (m, 2H).

Ex 1.11: [l-(4-Chloro-benzenesulfonyl)-piperidin-3-yl] -acetic acid λf'-phenyl- hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.74-7.64 (m, 2H); 7.51 -7.46 (m, 3H); 7.25-7.22 (m,

IH); 6.95-6.79 (m, 3H); 3.21-3.1 1 (m, 2H); 3.01-2.95 (m, I H); 2.77-2.73 (m. I H);

2.48-2.41 (m, IH); 2.30-2.25 (m, IH); 2.21-2.15 (m, I H); 1.73-1 .53 (m, 2H); 1.29-1.14

(m, IH); 0.87-0.83 (m, IH). Ex 1.12: [l-(4-Chloro-benzenesulfonyl)-piperidin-3-yI]aceticacid N"-(2,4- dichlorophenylphenyl) hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.67 (d, J = 8.54 Hz, I H); 7.52 (d, J = 8.59 Hz, 2H);

7.31 (d, J=I 1.9 Hz, IH); 7.16 (d, J= 8.79 Hz, IH); 6.9-6.82 (m, IH); 3.47 (d, J= 10.8

Hz, 2H); 3.49 (d, J = 4.66 Hz, 2H); 3.10-3.91 (m, 3H); 2.58-2.50 (m, IH); 2.23-2.18 (m, IH); 1.72-1.59 (m, 2H); 1.36-1.25 (m, IH); 0.86-0.77 (m, IH).

Ex 1.13: 7V-azepan-l-yl-2-[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.89-7.79 (m, IH); 7.58-7.56 (m, IH); 7.26-7.22 (m,

IH); 6.44 (s, IH); 3.58-3.51 (m, 2H); 3.32-3.23 (m, IH); 3.04-2.82 (m, 3H); 2.82-2.74 (m, 2H); 2.66 (s, 3H); 2.62-2.59 (m, IH); 2.43-2.38 (m, 2H); 1.89-1.79 (m, IH); 1.77-

1.73 (m, IH); 1.67-1.54(m, 8H); 1.23-1.16(m, 2H); 0.85-0.76 (m, IH).

Ex 1.14: 2-(l- benzenesulfonyl-piperidin-3-yl)- iV-(4-niethyl piperidin-1-yl) acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.77-7.71 (m, 2H); 7.60-7.57 (m, IH); 7.54-7.50 (m,

2H); 6.04 (s, IH); 3.6-3.4 (m, IH); 3.3-3.1 (m, IH); 2.95-2.92 (m, 2H); 2.44-2.27(m, 5H); 1.75-1.72 (m, 4H); 1.68-1.58 (m, 3H); 1.52-1.33 (m, 3H); 0.95-0.87 (m, 4H).

Ex 1.15: [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] -acetic acid N'(4- chloro phenyl) hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.77 (m, IH); 7.58-7.50 (m, 2H); 7.24-7.17 (m,

3H); 6.80-6.72 (m, 2H); 6.10-6.09 (m, IH); 3.34-3.31 (m, IH); 3.24-3.21 (m, 2H); 3.02-2.97 (m, IH); 2.65 (s, 3H); 2.49-2.43 (m, IH); 2.26-2.14 (m, 2H); 1.81-1.75 (m,

2H); 1.7-1.52(m, IH); 1.41-1.32 (m, IH).

Ex 1.16: [l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl] -acetic acid N'(2- chloro phenyl) hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.81-7.79 (m, IH); 7.60-7.56 (m, IH); 7.51 (d, J= 3.2 Hz, IH); 7.29-7.21 (m, 2H); 7.16-7.14(m, IH); 6.91-6.89 (m, IH); 6.85-6.83 (m, IH); 6.49 (d, J = 3.2 Hz, IH); 3.33-3.23 (m, IH); 3.1-2.75 (m, 2H); 2.66 (s, 3H); 2.50-2.45 (m, IH); 2.28-2.17 (m, 2H); 1.9-1.7(m, 3H); 1.5-1.31 (m, IH); 1.28-1.09 (m, IH).

Ex 1.17: l-{2-[l-(3-Chloro-2 -methyl benzenesulfonyl)-piperidin-3-yl]-acetylamino}- piperidin3-carboxylic acid, methyl ester

IH NMR: (CDCl ₃ , 400 MHz) δ 7.87-7.80 (m, IH); 7.58-7.56 (m, I H); 7.24-7.22 (m,

IH); 6.5-6.35 (m, IH); 3.71 (s, 3H); 3.53-3.50 (m, 2H); 3.38-3.3 (m, IH); 3.24-3.20(m, IH); 2.81-2.79 (m, IH); 2.66 (s, 3H); 2.63-2.57 (m, I H); 2.39-2.31 (m, I H); 2.29-2.21

(m, IH); 2.13-2.09 (m, IH); 2.02-1.97 (m, IH); 1.86-1.84 (m, IH); 1.78-1.69 (m, 3H);

1.66-1.61 (m, 3H); 1.3-1.1 l(m, IH); 1.01-0.85 (m, IH); 0.84-0.68 (m, IH).

Ex 1.18: 2-(l- benzenesulfonyl)-piperidin-3-yl)- λ ^L (3 -methyl piperidinl-yl)acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.77-7.72 (m, 2H); 7.60-7.57 (m, IH); 7.54-7.51 (m, 2H); 6.3(s, IH); 3.54-3.52 (m, IH); 3.01-2.96 (m, 3H); 2.51-2.31 (m, 3H); 2.29-2.17

(m, 2H); 2.09-2.04 (m, IH); 1.97-1.86 (m, 2H); 1.76-1.60 (m, 6H); 1.4-1.2 (m, IH);

1.0-0.8 (m, 4H).

Ex 1.19: 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- N-(hexahydro cyclopenta[c] pyrrole-2-yl)-acetamide 1H-νMR: (CDCl ₃ , 300 MHz) δ 7.88-7.86 (m, IH); 7.58-7.56 (m, IH); 7.26-7.22 (m,

IH); 5.85 (s, IH); 3.58-3.55 (m, 2H); 3.23-3.20 (m, 2H); 2.95-2.80 (m, 2H); 2.67-2.60

(m, 2H); 2.66 (s, 3H); 2.60-2.54 (m, 3H); 2.41-2.33 (m, 3H); 2.18-2.11 (m, IH); 1.78-

1.77 (m, IH); 1.75-1.72 (m, IH); 1.65-1.57(m, 2H); 1.48-1.40(m, IH), 1.38-1.26(m,

2H); 0.85-0.77 (IH, m). Ex 1.20: 2[l-(3-Chloro-2-methyl benzenesulfonyl)-piperidin-3-yl]- JV-(4-methyl piperidin 1 -yl)acetamide

IH νMR: (CDCl ₃ , 300MHz) δ 7.88-7.78 (m, IH); 7.58-7.56 (m, IH); 7.26-7.22 (m,

IH); 6.5 (s, IH); 3.54-3.50 (m, 2H); 2.96-2.81 (m, 2H); 2.78-2.65 (m, IH); 2.66 (s,

3H); 2.64-2.56 (m, IH); 2.45-2.21 (m, 4H); 2.12-2.09 (m, IH); 1.88-1.85 (m, IH); 1.77-1.72(m, IH); 1.68-1.63 (m, 2H); 1.6-1.4(m, 2H); 1.4-1.2 (m, 2H); 1.25-1.1 (m,

IH); 0.9-1 (m, 311).

Ex 1.21 : 1 -[2-(I - ben/enesui fbiiyl-piperidiii 3 yl) ucelylaminυ]-piperidin-3-curboxylic acid

IH νMR: (DMSO-^, 400 MHz) δl2.30 (s, IH); 8.88-8.84 (m, IH); 7.70-7.68 (m, 3H); 7.65-7.61(m, 2H); 3.51-3.31 (m, 2H); 3.01-2.99 (m, IH); 2.81-2.80 (m, IH); 2.60-2.55

(m, IH); 2.31-2.22 (m, 2H); 2.03-1.97 (m, IH); 1.87-1.75 (m, 4H); 1.66-1.48 (m, 5H);

1.3-1.05 (m, 2H); 0.8-1.0 (m, IH).

Ex 1.22: l-[2-(l- benzenesulfonyl-piperidin-S-y^-acetylaminoj-piperidin-S-carb oxylic acid amide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.53-8.76 (bs, IH); 7.73-7.71 (m, 2H); 7.61 -7.59 (m,

IH); 7.56-7.52(m, 2H); 6.98-7.02 (m, IH); 6.4-6.2(m, I H); 5.5-5.3 (m, I H); 3.48-3.03 (m, 2H); 2.93-2.70 (m, 2H); 2.67-2.66 (m, I H); 2.64-2.43 (m, 3H); 2.41 -2.37 (m, 1 H);

2.28-2.26 (m, IH); 2.07-2.04 (m, 2H); 1.77-1.60 (m, 5H); 1.5-1.32(m,lH); 1.31 -

1.25(m,lH).

Ex 1.23: 2-(l- benzenesulfonyl)-piperidin-3-yl)- N-(2-methyl piperidinl-yl)acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.61-7.57 (m, IH); 7.54-7.50 (m, 2H); 5.88(s, IH); 3.49-3.11 (m, IH); 3.05-2.54 (m, 2H); 2.52-2.44 (m, 2H); 2.37-2.20

(m, 4H); 1.78-1.65 (m, 8H); 1.61-1.57 (m, IH); 1.33-1.25 (m, 2H); 1.21-1.12 (m, 3H).

Ex 1.24: 2-[l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl]-λ ^r -piperidin-l-yl-acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.8-7.9 (m, 2H); 7.1(d, J= 8.64 Hz, 2H); 6.10 (bs, IH);

3.9 (s, 3H); 3.48-3.41 (m; 2H); 2.26-2.48 (m, 5H); 1.99-2.03 (m, 5H); 1.60 - 1.72 (m, 6H); 1.04-1.41 (m, 3H).

Ex 1.25: 2-[l -(4-Methoxy-benzenesulfonyl)-piperidin-3-yl]-iV-morpholin-4- yl- acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.64-7.70 (m, 2H); 7.01(d, J= 8.68 Hz, 2H); 6.57 (bs,

IH); 3.87 (s, 3H); 3.83-3.85 (m, 2H); 3.19-3.36 (m, IH); 2.88-2.94 (m, 4H); 2.31 - 2.26 (m 5H); 1.73-2.00 (m, 2H); 1.07-1.37 (m, 5H).

Ex 1.26: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid iV-(2,4-dichloro-phenyl)- hydrazide

IH NMR: (DMSO-J ₆ , 300 MHz) δ 9.82 (s, IH); 7.68 (m, 5H); 7.41(d, J= 2.31Hz, 2H);

7.20 (dd, J= 2.2, 8.74 Hz, IH); 6.70 (d, J = 8.7 Hz, IH); 2.33 (m, IH); 2.11 (m, 3H); 1.97 (m, 2H); 1.66 (m, 2H); 1.47 (m, IH); 1.22 (m, IH); 0.99 (m, IH).

Ex 1.27: [l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl] -acetic acid iV-phenyl- hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.69-7.64 (m, 2H); 7.48-7.44 (m, IH); 7.31-7.22 (m, 2H); 7.00-6.82 (m, 5H); 6.15 (m, IH); 3.87 (s, 3H); 3.11-3.02 (m, 2H); 2.78-2.70 (m, IH); 2.52-2.45 (m, IH); 2.29 (m, IH); 2.21-2.14 (m, IH); 1.71-1.53 (m, 4H); 1.28-1.25 (m, IH).

Ex 1.28: [l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl] -acetic acid iV-cyclohexyl- hydrazide

IH NMR: (DMSO-d6, 300 MHz) δ 9.28 (s, IH); 7.62 (d, J = 8.82 Hz, 2H); 7.14 (d, J = 8.79 Hz, 2H); 3.84 (s, 3H); 3.42-3.45 (m, 2H); 2.71-2.59 (m, I H); 2.25-2.21 (m, I H); 1.93-2.07 (m, 4H); 1.69-1.45 (m, 8H); 1.28-0.85 (m, 6H).

Ex 1.29: 2-[l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl]-N-pyrrolidi n-l-yl- acetamide

IH NMR: (DMSO-d6, 300 MHz) δ 8.75 (s, IH); 7.62 (d, J = 7 Hz, 2H); 7.16 (d, J = 7 Hz, 2H); 3.83 (s, 3H); 3.55-3.38 (m, 2H); 2.76-2.74 (m, 4H); 2.26-2.24 (m, 2H); 1.96- 1.87 (m, 3H); 1.69-1.54 (m, 6H); 1.52-1.44 (m, III); 0.86-0.74(m, IH). Ex 1.30: [l-(4-Trifluoromethoxy-benzenesulfonyl)-piperidin-3-yl]-acet ic acid W-(2,4- dichloro-phenyl)-hydrazide

IH NMR: (DMSO-J ₆ , 300 MHz) δ 9.83 (s IH); 7.86 (d, J = 8.73 Hz, 2H); 7.64 (d, J = 8.76 Hz, 2H); 7.41(d, J= 2.25 Hz, 2H); 7.20 (dd, J= 2.23, 8.76 Hz, IH); 6.77-6.68 (m, IH); 3.53-3.39 (m 2H); 2.40-2.36 (m, IH); 2.25-2.12 (m, 3H); 1.99-1.97 (m, IH); 1.68- 1.66 (m, 2H); 1.48-1.46 (m, IH); 1.04-1.00 (m, IH). Ex 1.31 : N-Piperidin-l-yl-2-[l-(4-trifluoromethoxy-benzenesulfonyl)-p iperidin-3-yl]- acetamide

IH NMR: (DMSO-J ₆ , 300 MHz) δ 8.72 (bs, IH); 7.85 (d, J= 8.85 Hz, 2H); 7.62 (d, J

= 8.25 Hz, 2H,); 3.52-3.31 (m, 2H); 2.71-2.70 (m, IH); 2.64-2.60 (m, 3H); 2.38-2.34

(m, 2H); 2.24-2.22 (m, IH); 2.08-2.06 (m, IH); 1.88-1.86 (m, 2H); 1.64-1.51 (m, 7H); 1.30-1.22 (m, IH); 0.95-0.93 (m, IH).

Ex 1.32: iV-Moφholin-4-yl-2-[l-(4-trifluoromethoxy-benzenesulfonyl)- piperidin-3-yl]- acetamide

IH NMR: (DMSO-J ₆ , 300 MHz) δ 8.89 (bs, IH); 7.86 (d, J= 8.70 Hz, 2H); 7.62 (d, J

= 8.37 Hz, 2H); 3.59-3.39 (m, 5H); 2.71-2.68 (m, 4H); 2.40-2.36 (m, IH); 2.33-2.28 (m, IH); 2.12-2.08 (m, IH); 1.89 (s, 2H); 1.64-1.46 (m, 3H); 1.24-1.22 (m, IH); 0.95-

0.93 (m, IH).

Ex 1.33: [l-(4-Trifluoromethoxy-benzenesulfonyl)-piperidin-3-yl] -acetic acid N ¹ - phenyl-hydrazide

IH νMR: (DMSO-J ₆ , 400 MHz) δ 9.62 (s, IH); 7.86-7.83 (m, 2H); 7.7 (s, IH); 7.64- 7.62 (m, 2H); 7.13-7.09 (m, 2H); 6.69-6.66 (m, 3H); 3.53-3.41 (m, 2H); 2.39-2.40 (m,

IH); 2.20-2.09 (m, 4H); 1.98-1.96 (m, 2TT); 1.68-1.62 (m, III); 1.23-1.21(m, III).

Ex. 1.34: [l-(4-Trifluoromcthoxy-bcnzcncsulfonyl)-pipcridin-3-yl] -acetic acid N ¹ - cyclohexyl-hydrazide

IH NMR: (DMSO-J ₆ , 400 MHz) δ 9.24 (s, IH); 7.83 (d, J = 6.8 Hz, 2H); 7.62 (d, J = 6.2 Hz, 2H); 4.70 (s, IH); 3.46-3.45 (m, 2H); 2.49-2.48 (m, I H); 2.34-2.33 (m, I H); 2.08-2.05 (m, IH); 1.97-1.91 (m, 3H); 1.71-1.64 (m, 8H); 1.22-1.1 l (m, 3H); 1.01-0.99

(m, 3H). Ex 1.35: N-Pyrrolidin-l-yl-2-[l -(4-trifluoromethoxy-benzenesυlfonyl)-piperidin-3-yl]- acetamide

IH νMR: (DMSO-J ₆ , 400 MHz) δ 8.71 (bs, IH); 7.86-7.83 (m, 2H); 7.63-7.60 (m,

2K); 3.44-3.32 (in, 2H); 3.32-3.29 (m, IH); 2.74-2.73 (m, 3H); 2.27-2.26 (m, IH);

2.26-2.25 (m, IH); 2.08-2.06 (m, IH); 1.88 (s, 2H); 1.69-1.68 (m, 6H); 1.65-1.64 (m, IH); 0.95-0.93 (m, IH).

Ex. 1.36: [l-(4-Methoxy-benzenesulfonyl)-piperidin-3-yl] -acetic acid 7V-(2,4-dichloro- phenyl)-hydrazide

IH νMR: (DMSO-J ₆ , 400 MHz) δ 9.82 (s IH); 7.63 (d, J = 8.8Hz, 2H); 7.40 (d, J =

2.4 Hz, 2H); 7.20-7.14 (m, 3H); 6.70 (d, J = 8.8 Hz, IH); 3.83 (s, 3H); 3.47-3.45 (m, 2H); 2.29 (m, 1 H); 2.12-2.08 (m, 2H); 2.08-2.05 (m, 1 H); 1.68- 1.65 (m, 2H); 1.42- 1.40

(m, IH); 1.0-0.98 (m, IH).

Ex. 1.37: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid iV-(2-chloro-phenyl)- hydrazide

IH νMR: (DMSO-J ₆ , 400 MHz) δ 9.80 (s, IH); 7.87-7.62 (m, 5H); 7.41 (s, IH); 7.29 (d, J= 7.7Hz, IH); 7.17-7.12 (m, IH); 6.77-6.72 (m, 2H); 3.52 (d, J= 8 Hz, IH); 3.43-

3.40 (m, IH); 2.36-2.31 (m IH); 2.13-2.09 (m, 3H); 2.00-1.97 (m, IH); 1.70-1.63 (m,

2H); 1.50-1.43 (m, IH); 1.03-1.01(m, IH).

Ex. 1.38: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid iV-(3-chloro-phenyl)- hydrazide IH νMR: (DMSO-J ₆ , 400 MHz) δ 9.70 (s, IH); 8.04 (s, IH); 7.72-7.62 (m, 5H); 7.13

(t, J = 8 Hz, IH); 6.71 (dd, J = 1.2, 8 Hz, IH); 6.66-6.61 (m, 2H); 3.44-3.29 (m, IH);

3.32-3.30 (m, IH); 2.36-2.31 (m IH); 2.13-2.10 (m, 3H); 2.09-2.08 (m, IH); 1.97-1.95

(m, 2H); 1.88-1.90 (m, IH); 1.03-1.00(m, IH).

Ex 1.39: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid jV-(3-chloro-4-methyl-phenyl)- hydrazide

1H-νMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.64-7.52 (m, 4H); 7.10 (d, J= 8.4

Hz, IH); 6.89 (s, IH); 6.69 (dd, J = 2.4, 8.4 Hz, IH); 6.11 (s, IH); 3.10-3.02 (m, 2H);

3.88-3.85 (m, IH); 2.53-2.48 (m, I H); 2.29-2.27 (m 3H); 2.19-2.15 (m, I H); 1.76-1.59

(m, 5H); 1.32-1.31 (m, IH).

Ex 1.40: l-[2-(l-Benzenesulfonyl-piperidin-3-yl)-acetylamino]-piperid ine-3-carboxylic acid, methyl ester IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.90 (bs, IH); 7.72-7.61 (m, 5H); 3.59 (s, 3H);

3.58-3.49 (m, IH); 3.05-3.02 (m, I H); 3.49 (bs, IH); 2.87 (s, I H); 2.65-2.53 (m, I H);

2.32-2.21 (m, 2H); 2.06-2.02 (m, 2H); 1.87-1.84 (m, 2H); 1.83-1.80 (m, I H); 1.68-1.60

(m, 5H); 1.40-1.36 (m, 2H); 1.00-0.93 (m, IH).

Ex. 1.41 : 2-[l-(3,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-7V-piper idin-l -yl- acetamide

IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.7-9.0 (bs, IH); 7.9-7.88 (m, 2H); 7.0-7.66 (m,

IH); 3.46-3.37 (m, 2H); 3.32-3.27 (m, 2H); 2.63-2.61 (m, 2H); 2.49-2.48 (m, 2H); 2.40

- 2.25 (m, IH); 2.24-2.22 (m, IH); 1.87-1.63 (m, 9H); 1.53-1.51 (m, IH); 1.0 - 0.98 (m,

IH). Ex: 1.42: 2-(l-Benzenesulfonyl-piperidin-3-yl)-N-(4-phenyl-piperidin-l -yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.75 (m, 2H); 7.58-7.50(m, 3H); 7.31-7.30 (m,

2H); 7.25-7.20 (m, 3H); 6.99 (s, IH); 3.48-3.44 (m, IH); 3.22-3.17 (m, IH); 2.81-2.77

(m, IH); 2.57-2.49 (m, IH); 2.44-2.36 (m, 3H); 2.17-2.15 (m, IH); 1.90-1.84 (m, IH);

1.76-1.25 (m, 8H); 1.14-1.11 (m, 2H); 0.98-0.95 (m, IH). Ex. 1.43: 2-(l-Benzenesulfonyl-piperidin-3-yl)-l-piperidin-l-yl-ethano ne

IH NMR: (CDCl ₃ , 400 MHz) δ 7.71-7.68 (m, 3H); 7.64-7.61 (m, 2H); 3.53-3.51 (d, J=

9.2 Hz, IH); 3.45-3.37 (m, 3H); 3.32-3.27 (m, 2H); 2.31-2.24 (m, 2H); 2.20-2.17 (m,

2H); 2.05-2.00 (t, J= 10 Hz, IH); 1.93-1.91 (m, IH); 1.66-1.57 (m, 4H); 1.55-1.44 (m,

4H); 0.97-0.89 (m, IH). Ex: 1.44: 2-(l -Benzenes ulfonyl-piperidin-3-yl)-N-(4-benzyl-piperidin-l-yl)-acetamid e

IH νMR: (CDCl ₃ , 400 MHz) δ 7.77-7.70 (m, 2H); 7.61-7.50 (m, 3H); 7.30-7.26 (m,

2H); 7.22-7.12 (m, 3H); 6.42 (s, IH); 3.52-3.43 (m, IH); 3.19-3.15 (m, IH); 2.91- 2.88(m, 3H); 2.55-2.54 (m, 2H); 2.43-2.30 (m, 3H); 2.24-2.18 (m, 2H); 2.17-2.01 (m,

IH); 1.99-1.70 (m, 4H); 1.61-1.52 (m, IH); 1.50-1.34(m, 2H); 1.10-1.0 (m, IH), 0.97- 0.89 (m, IH).

Ex 1.45: 2-[l-(3-Chloro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-( 4-phenyl- piperidin- 1 -yl)-acetamide

IH NMR: (DMSO-d* 400 MHz) δ 8.83 (s, IH); 7.80-7.74 (m, 2H); 7.45-7.43 (m, IH);

7.30-7.25 (m, 4H); 7.19-7.17 (m, IH); 3.54-3.46 (m, 2H); 3.20-3.15 (m, I H); 2.92-2.90

(m, 2H); 2.75-2.48 (m, 5H); 2.32-2.30 (m, IH); 1.91-1.82 (m, 2H); 1.72-1.66 (m, 6H);

1.54-1.52 (m, IH); 1.22-1.12 (m, 2H); 1.10-1.0 (m, I H). Ex 1.46: 2-(l-Benzenesulfonyl-piperidin-3-yl)-7V-moφholin-4-yl-aceta mide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.77-7.71 (m, 2H); 7.62-7.51 (m, 3H); 6.59 (bs, IH);

3.85-3.82 (m, 2H); 3.52-3.38 (m, IH); 3.25-2.85 (m, 4H); 2.65-2.55 (m, 2H); 2.43-2.35

(m, IH); 2.26-2.17 (m, IH); 1.77-1.73 (m, 3H); 1.70-1.62 (m, IH); 1.58-1.55 (m, IH);

1.40-1.35 (m, IH); 1.28-1.25 (m, IH); 1.15-1.05 (m, IH). Ex 1.47: 2-[l-(4-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-piperidin- l-yl-acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.71-7.65 (m, 2H); 7.51-7.48 (d, J= 8.55 Hz, 2H); 6.10 (bs, IH); 3.50-3.45 (m, IH); 3.20-2.92 (m, 3H); 2.77-2.7 (m, 2H); 2.55-2.45 (m, IH); 2.43-2.01 (m, 4H); 1.76-1.62 (m, 7H); 1.41-1.25 (m, 2H); 1.15-1.05 (m, IH). Ex 1.48: 2-[l-(4-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-moφholin- 4-yl-acetamide IH NMR: (CDCl ₃ , 300 MHz) δ 7.71-7.68 (m, 2H); 7.51 (d, J= 8.26 Hz, 2H); 3.85-3.76 (m, 4H); 3.52-3.40 (m, IH); 3.20-2.92 (m, 4H); 2.71-2.63 (m, IH); 2.63-2.53 (m, IH); 2.44-2.38 (m, IH); 2.35-2.31 (m, IH); 1.77-1.73 (m, 2H); 1.55-1.58 (m, IH); 1.35-1.40 (m, IH); 1.25-1.28 (m, IH); 1.05-1.15 (m, IH).

Ex 1.49: (l-Benzenesulfbnyl-piperidin-3-yl)-acetic acid iV-phenyl-hydrazide IH NMR: (CDCl ₃ , 300 MHz) δ 7.78-7.73 (m, 2H); 7.60-7.49 (m, 3H); 7.31-7.22 (m, 2H); 6.96-6.79 (m, 3H); 6.12-6.15 (m, IH); 3.16-3.05 (m, 3H); 2.83-2.61 (m, IH); 2.51-2.44 (m, IH); 2.29-2.21 (m, IH); 2.19-2.15 (m, IH); 1.72-1.65 (m, 2H); 1.37-1.25 (m, 2H).

Ex 1.50: Adamantane-1-carboxylic acid 7V-[2-(l-benzenesulfonyl-piperidin-3-yl)- acetylj-hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 9.22 (d, J = 6.09 Hz, IH); 8.49 (d, J = 6.11 Hz, IH); 7.75 (d, J = 8.28 Hz, 2H); 7.62-7.49 (m, 3H); 3.48-3.37 (m, 2H); 2.58-2.55 (m, IH); 2.48-2.41 (m, IH); 2.34-2.29 (m, IH); 2.22-2.16 (m, 2H); 2.04-1.98 (m, 4H); 1.73-1.6 (m, 13H); 1.37-1.25 (m, IH); 1.10-1.07 (m, IH). Ex. 1.51: 4-Chloro-benzoic acid 7V-[2-(l-benzenesulfonyl-piperidin-3-yl)-acetyl]- hydrazide

IH NMR: (DMSO-J ₆ , 300 MHz) δ 10.43 (s, IH); 9.92 (s, I H); 7.87 (d, J = 8.50 Hz, 2H); 7.74-7.61 (m. 5H); 7.57 (d, J = 8.5 Hz, 2H); 3.61 -3.44 (m, 3H); 2.27-2.23 (m, IH); 2.1 1-2.03 (m, 3H); 1.98-1.90 (m, IH); 1.70-1.67 (m, 2H); 1.50-1.45 (m, IH). Ex 1.52: [l-(2-Fluoro-4-methoxy-benzenesulfonyl)-piperidin-3-yl]-acet ic acid 7V-(2,4- dichloro-phenyl)-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.73 (t, J= 8.4 Hz, IH); 7.60 (d, J = 2.8 Hz, IH); 7.29 (d, J= 2.4 Hz, IH); 7.15 (dd, J= 2.4, 8.8 Hz, IH); 6.91 (d, J= 8.4 Hz, IH); 6.76 (dd, J = 8.8 Hz, 2.4 Hz, IH,); 6.70 (dd, J = 2.4, 12 Hz, IH); 6.45 (d, J = 3.2 Hz, IH); 3.90- 3.86 (m, 3H); 3.33-3.31 (m, IH); 3.14-3.03 (m, 3H); 2.61-2.55 (m, IH); 2.33-2.31 (m, IH); 2.21-2.16 (m, IH); 1.78-1.68 (m, 2H); 1.65-1.61 (m, IH); 1.45-1.43 (m, IH). Ex 1.53: N- Azepan- 1 -yl-2-( 1 -benzenesulfonyl-piperidin-3 -yl)-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.61-7.57 (m, IH); 7.54-7.51 (m, 2H); 6.47 (s, IH); 3.54-3.44 (m, IH); 3.06-3.01 (m, 4H); 2.99-2.77 (m, IH); 2.75-2.36 (m, 3H); 2.35-2.19 (m, IH); 1.78-1.54 (m, 13H). Ex 1.54: 2-( 1 -Benzenesulfonyl-piperidin-3 -yl)-N-(3-hydroxymethyl-piperidin-l-yl)- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.61-7.57 (m, IH); 7.55-7.51 (m, 2H); 6.61 (s, IH); 6.21 (s, IH); 3.58-3.56 (m, IH); 3.44-3.41 (m, IH); 3.37-3.31 (m, IH); 3.16-3.14 (m, IH); 3.04-2.98 (m, IH); 2.98-2.93 (m, IH); 2.60-2.50 (m, IH); 2.45-2.41 (m, IH); 2.36-2.29 (m, IH); 2.26-2.21 (m, 2H); 2.04-1.99 (m, 2H); 1.79-1.57 (m, 8H); 1.11-1.07 (m, IH).

Ex 1.55: (1 -Benzenesulfonyl-piperidin-3 -yl)-acetic acid iV-(2,4-dimethyl-phenyl)- hydrazide IH NMR: (CDC13, 400 MHz) δ 7.76-7.71 (m, 2H); 7.61-7.57 (m, IH); 7.54-7.49 (m, 3H); 6.94-6.90 (m, 2H); 6.28-6.68 (m, IH); 6.03-5.94 (m, IH); 3.20-3.17 (m, IH); 3.17-3.08 (m, IH); 2.98-2.94 (m, IH); 2.82-2.73 (m, IH); 2.47-2.44 (m, IH); 2.29-2.14 (m, 8H); 1.77-1.57 (m, 3H); 1.28-1.25 (m, IH).

Ex 1.56: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid JV-(2,3-dimethyl-phenyl)- hydrazide IH NMR: (CDCl ₃ , 400 MHz) δ 7.76-7.72 (m, 2H); 7.61-7.57 (m, IH); 7.54-7.47 (m, 3H); 7.09-7.01 (m, IH); 6.80-6.74 (m, 2H); 6.13-6.05 (m, IH); 3.21-3.09 (m, 2H); 2.99-2.74 (m, 2H), 2.49-2.43 (m, IH), 2.31-2.27 (m, 4H), 2.21-2.14 (m, 4H), 1.78-1.58 (m, 3H), 1.30-1.25 (m, IH).

Ex 1.57: N-Azepan-l-yl-2-(l-benzenesulfonyl-piperidin-3-yl)-acetamide , hydrochloride salt

IH NMR: (CDCl ₃ , 400 MHz) δ 12.0 (bs, IH); 7.75-7.73 (m, 2H); 7.63-7.59 (m, I H);

7.56-7.52 (m, 2H); 3.92-3.89 (m, 4H); 3.53-3.38 (m, 2H); 2.50-2.37 (m, 4H); 2.19-2.12 (m _; 5H); 1.78-1.54 (m, 8H); 1.30-1.22 (m, IH).

Ex 1.58: 2-(l -Benzenesulfonyl-piperidin-3-yl)-N-(3-benzyloxymethyl-piperi din-l -yl)- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.59-7.41 (m, 3H); 7.47-7.38 (m,

5H); 5.11-5.08 (m, IH); 4.84-4.81 (m, IH); 4.02-4.00 (m, IH); 3.66-3.54 (m, 3H); 3.47-3.35 (m, IH); 3.3-3.0 (m, IH); 2.74-2.68 (m, IH); 2.53-2.48 (m, IH); 2.31-1.86

(m, 7H); 1.75-1.60 (m, 5H); 0.97-0.96 (m, 2H).

Ex 1.59: 2-(l-Benzenesulfonyl-piperidin-3-yl)-N-piperidin-l-yl-acetam ide. [(+)-

Isomer]

IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.59-7.57 (m, IH); 7.54-7.50 (m, 2H); 6.12 (bs, IH); 3.54-3.45 (m, IH); 3.14-3.01 (m, IH); 2.99-2.91 (m, 2H); 2.77 (bs,

2H); 2.51-2.44 (m, IH); 2.43-2.35 (m, 2H); 2.33-2.17 (m, 2H); 1.78-1.60 (m, 7H);

1.42-1.41 (m, IH); 1.30-1.25 (m, IH); 1.10-1.05 (m, IH).

Ex 1.60: 2-(l-Benzenesulfonyl-piperidin-3-yl)-N-piperidin-l-yl-acetam ide. [(-)-isomer]

IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.59-7.57 (m, IH); 7.54-7.50 (m, 2H); 6.07 (bs, IH), 3.54-3.45 (m, IH); 3.14-3.01 (m, IH); 2.99-2.91 (m, 2H); 2.77 (bs,

2H); 2.51-2.44 (m, IH); 2.43-2.35 (m, 2H); 2.33-2.17 (m, 2H); 1.78-1.60 (m, 7H);

1.42-1.41 (m, IH); 1.30-1.25 (m, IH); 1.10-1.05 (m, IH).

Ex 1.61: 2-(l-Benzenesulfonyl-piperidin-3-yl)-iV-(3-methyl-piperidin- l-yl)-acetamide,

[(-)- isomer] IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.72 (m, 2H); 7.59-7.57 (m, IH); 7.54-7.50 (m,

2H); 6.04(bs, IH); 3.53-3.44 (m, IH); 3.16-3.07 (m, IH); 2.98-2.94 (m, 2H); 2.60-2.50

(m, IH); 2.42-2.28 (m, 2H); 2.18-2.17 (m, IH); 2.04-2.03 (m, IH); 1.90-1.81 (m, IH);

1.77-1.58 (m, 7H); 1.33-1.25 (m, 2H); 1.10-1.05 (m, IH); 0.93-0.85 (m, 3H).

Ex 1.62 : 2- [ 1 -(4-Fluoro-benzenesulfonyl)-piperidin-3 -yl] -N-piperidin- 1 -yl-acetamide IH NMR: (CDCl ₃ , 300 MHz) δ 7.8-7.72 (m, 2H); 7.26-7.1 (m, 2H); 6.09 (bs, IH);

3.53-3.50 (m, IH); 2.98-2.89 (m, 3H); 2.78-2.74 (m, IH); 2.5-2.47 (m, IH); 2.42 -

2.38(m IH); 2.34-2.28 (m, 3H); 1.73-1.70 (m, 7H); 1.48-1.45 m, IH); 1.28-1.23 (m,

IH); 1.09-1.04 (m, IH); 0.89-0.85 (m, IH).

Ex 1.63: 2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3'yl]-N-morpholin- 4-yl-acetamide IH NMR: (CDCl ₃ , 300 MHz) δ 7.80-7.72 (m, 2H); 7.24-7.18 (m, 2H); 6.55 (bs, I H); 3.85-3.82 (m, 3H); 3.43-3.49 (m, IH); 2.99-2.85 (m, 4H); 2.71-2.65 (m, 2H); 2.48-2.33 (m, 2H); 2.34-2.29 (m, 2H); 1.78-1.65 (m, 2H); 1.28-1.23 (m, IH); 1.09-1.04 (m, I H); 0.89-0.85 (m, I H).

Ex 1.64: [l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid 7V-phenyl-hydrazide IH NMR: (CDCl ₃ , 300 MHz) δ 7.78-7.75 (m, 2H); 7.46 (s, IH); 7.23-7.19 (m, 3H); 6.9-6.79 (m, 3H); 6.15 (d, J = 3.87 Hz, IH); 3.19-3.10 (m, 2H); 2.8-2.7 (m, IH); 2.47- 2.42 (m, IH); 2.29-2.17 (m IH); 1.7-1.6 (m, 3H); 1.37-1.25 (m, 3H). Ex 1.65: 2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-pyrrolidin -l-yl-acetamide IH NMR: (CDCl ₃ , 300 MHz) δ 7.80-7.72 (m, 2H); 7.26-7.18 (m, 2H); 5.99 (s, IH); 3.53-3.42 (m, 2H); 3.2-2.95 (m, IH); 2.9 (m, 3H); 2.56-2.49 (m, IH); 2.46-2.41 (m, IH); 2.37--2.30 (m, IH); 2.04-2.02 (m, IH); 1.88-1.75 (m, 7H); 1.27-1.23 (m, IH); 1.10-1.07 (m, IH). Ex 1.66: [l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid N-benzyl-hydrazide IH NMR: (CDCl ₃ , 300 MHz) δ 8.65 (bs, IH); 7.76-7.71 (m, 2H); 7.64-7.61 (m, IH); 7.35-7.32 (m, 3H); 7.23-7.2 (m, 3H); 5.53 (bs, IH); 3.57-3.54 (m, IH); 3.34-3.27 (m, IH); 3.18-2.97 (m, 2H); 2.42-2.17 (m, 3H); 2.09-2.02 (m, 3H); 1.78-1.63 (m, 2H); 1.14-1.08 (m, IH). Ex 1.67: [l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid iV-cyclohexyl- hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.78-7.73 (m, 2H); 7.27-7.71 (m, 2H); 7.09 (s, IH); 3.27-3.17 (m, 2H); 2.83-2.76 (m, 2H); 2.60-2.57 (m, IH); 2.28-2.24 (m, 2H); 2.08-2.04 (m, IH); 1.82-1.68 (m, 3H); 1.63-1.60 (m, 4H); 1.33-1.20 (m, 2H); 1.17-1.09 (m, 5H). Ex 1.68: [l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl] -acetic acid iV-(2,4-dichloro- phenyl)-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 9.83 (d, J = 1.2 Hz, IH); 7.8-7.76 (m, 2H); 7.63 (s, IH); 7.50-7.43 (m, 2H); 7.40 (d, J = 2.4 Hz, IH); 7.18 (dd, J = 2.4, 8.8 Hz, IH); 6.70 (d, J= 8.8 Hz, IH); 3.58-3.48 (m, IH); 3.41-3.38 (m, IH); 2.49-2.48 (in, III); 2.36 (m, 3H); 2.17-2.13 (m, 2H); 2.13-2.11 (m, 2H); 1.68-1.64 (m, IH).

Ex 1.69: 2-[l-(3 -Chloro-benzenesulfonyl)-piperidin-3 -yl] -iV-piperidin- 1 -yl-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.75-7.71 (m, IH); 7.65-7.63 (m, IH); 7.57-7.45 (m, IH); 7.49- 7.26 (m, IH); 6.08 (s, I H); 3.6-3.47 (m, 2H); 3.07-2.97 (m, 2H); 2.77 (m,

2H); 2.56-2.42 (m, IH); 2.40- 2.3 (m 2H); 2.29-2.18 (m, 2H); 1.8-1.56 (m, 8H); 1.09- 1.04 (m, IH); 0.89-0.85 (m, IH).

Ex 1.70 : 2- [ 1 -(3 -Chloro-benzenesulfonyl)-piperidin-3 -y 1 ] -λ/-morphol i n-4-y 1-acetam ide IH NMR: (CDCl ₃ , 400 MHz) δ 7.72 (dd, J = 1.6, 12 Hz, I H); 7.65-7.55 (m, 2H); 7.49- 7.35 (m, IH); 6.15 (s, I H); 3.85-3.82 (m, 3H); 3.43-3.49 (m, I H); 3.38-2.94 (m, 4H);

2.71-2.65 (m, IH); 2.48-2.37 (m, IH); 2.37-2.32 (m, I H); 2.34-2.29 (m, I H); 2.07-2.03

(m, 2H); 1.78-1.65 (m, 4H); 1.13-1.1 1 (m, IH).

Ex 1.71 : [l-(3-Chloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid λ ^/I -(2,4-dichloro- phenyl)-hydrazide IH NMR: (CDCl ₃ , 400 MHz) δ 7.7 (s, IH); 7.63-7.57 (m, 2H); 7.50-7.45 (m, 2H);

7.33-7.26 (m, IH); 7.16 (dd, J = 2.4, 8.8 Hz, IH); 6.89 (d, J = 8.4 Hz, IH); 6.47-6.44

(m, IH); 3.0-2.93 (m, 4H); 2.57-2.51 (m, IH); 2.23-2.21 (m, IH); 1.83-1.68 (m, 4H);

1.32-1.29 (m, IH).

Ex 1.72: 2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-7V-piperidin -l-yl-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.07-8.00 (m, IH); 7.52-7.40 (m, 2H); 7.40-7.36 (m,

IH); 6.05 (s, IH); 3.66-3.63 (m, IH); 3.31-3.25 (m, IH); 2.92-2.76 (m, 2H); 2.70-2.67

(m, 2H); 2.40-2.38 (m, IH); 2.38- 2.28 (m 3H); 1.82-1.86 (m, IH); 1.73-1.69 (m, IH);

1.66-1.65 (m, 4H); 1.63-1.59 (m, 3H); 1.43-1.41(m, IH); 1.25-1.22 (m, IH).

Ex 1.73: 2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-morpholin- 4-yl-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.06-7.99 (m, IH); 7.53-7.45 (m, 2H); 7.41-7.36 (m,

IH); 6.15 (s, IH); 3.84-3.81 (m, 4H); 3.65-3.54 (m, 3H); 3.19-3.16 (m, IH); 2.99-2.96

(m, 2H); 2.87-2.81 (m, IH); 2.79-2.76 (m, IH); 2.52-2.47 (m, IH); 2.41-2.33 (m, IH);

2.06-2.01 (m, IH); 1.75-1.71 (m, IH); 1.62-1.58 (m, IH); 1.43-1.39 (m, IH); 1.25-1.20

(m, IH). Ex 1.74: [l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid N'-(2,4-dichloro- phenyl)-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.02 (dd, J= 1.6, 6.4 Hz, IH); 7.64 (d, J= 2.8 Hz, IH);

7.54-7.47 (m, 2H); 7.41-7.37 (m, IH); 7.33-7.33 (m, IH); 7.13 (dd, J = 2.4, 8.8 Hz,

IH); 6.90 (d, J= 2 Hz, IH); _. 6.44 (d, J= 2.8 Hz, IH); 3.46-3.41 (m, IH); 3.33-3.23 (m, IH); 3.19-3.14 (m, 2H); 2.59-2.53 (m, IH); 2.30-2.28 (m, IH); 2.19-2.16 (m, IH);

1.80-1.75 (m, 2H); 1.63-1.57 (m, IH); 1.54-1.54 (m, IH).

Ex 1.75: 2-[l -(4-Fluoro-benzenesulfonyl)-piperidin-3 -yl] -N-(4-methyl-piperazin- 1 -yl)- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.72 (m, 2H); 7.22-7.18 (m, 2H); 6.07 (s, I H);

3.49 (s, 3H); 3.44-3.37 (m, IH); 3.05 -2.96 (m, 2H); 2.88-2.81 (m, 3H); 2.75-2.58 (m,

3H); 2.50-2.45 (m, 2H); 2.37- 2.31 (m, 5H); 1.77-1.70 (m, I H); 1.39-1.23 (m, I H);

1.17-1.11 (m, IH). Ex 1.76: N-Azepan-l -yl-2-[l-(4-fluoro-benzenesulfonyl)-piperidin-3-yl]-acetamid e

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.73 (m, 2H); 7.22-7.18 (m, 2H); 6.48 (s, IH);

3.54-3.44 (m, IH); 3.09-3.02 (m, 3H); 2.81-2.78 (m, IH); 2.57-2.49 (m, IH); 2.47-2.42

(m, 2H); 2.40-2.31 (m, IH); 1.80-1.75 (m, 7H); 1.68-1.58 (m, 5H); 1.35-1.25 (m, IH);

1.4-1.07 (m, IH). Ex 1.77: 2-[l-(3,5-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-piperi din-l-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.73 (s, IH); 8.03-8.01 (m, IH); 7.70-7.68 (m, 2H);

3.49-3.46 (m, 2H); 2.87 (m, IH); 2.64-2.61 (m, 3H); 2.26-2.23 (m, 2H); 1.88 (m, 2H);

1.60- 1.44 (m, 1 OH); 0.9- 1.1 (m, 1 H). Ex 1.78: 2-[l-(3,5-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-moφho lin-4-yl- acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 7.62-7.62 (m, IH); 7.58-7.56 (m, 2H); 6.16 (s, IH); 3.86-3.84 (m, 2H); 3.80-3.50 (m, IH); 3.47-3.43 (m, IH); 3.2 (m, IH); 3.02-2.90. (m, 4H); 2.72 (m, IH); 2.59-2.51 (m, 2H); 2.40-2.34 (m, IH); 2.09 (m, IH); 1.80-1.75 (m, 3H); 1.40-1.35 (m, IH); 1.25-1.14 (m, IH).

Ex 1.79: 2-( 1 -Benzenesulfonyl-piperidin-3-yl)-N-(3 ,4-dihydro- 1 H-isoquinolin-2-yl)- acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 7.75-7.70 (m, 2H); 7.61-7.59 (m, 3H); 7.20-7.13 (m, 3H); 7.06-7.04 (m, IH); 6.39 (s, IH); 4.23-4.21 (m, IH); 3.37-3.33 (m, 3H); 3.12-3.11 (m, 2H); 2.95-2.88 (m, 3H); 2.49-2.46 (m, 2H); 2.35 (m, IH); 2.17-2.16 (m, IH); 1.75- 1.71 (m, IH); 1.65-1.63 (m, IH); 1.56-1.25 (m, IH); 1.1-1.07 (m, IH). Ex 1.80: 2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-(4-methyl- piperidin-l-yl)- acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 8.06-8.00 (m, IH); 7.52-7.46 (m, 2H); 7.40-7.26 (m, IH); 6.05 (s, IH); 3.67-3.61 (m, IH); 3.24 (m, IH); 3.13-3.10 (m, IH); 2.95-2.91 (m, 2H); 2.72-2.66 (m, IH); 2.43- 2.37 (m, 2H); 2.31-2.30 (m, 2H); 2.28-2.25 (m, IH); 1.95-1.99 (m, IH); 1.75-1.74 (m, IH); 1.65-1.62 (m, 7H); 1.58-1.52 (m, 2H); 1.13-1.08 (m, IH).

Ex 1.81 : N-Piperidin-l-yl-2-[l-(toluene-2-sulfonyl)-piperidin-3-ylJ-a cetamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.91-7.81 (m, IH); 7.46-7.42 (m, I H); 7.35-7.28 (m, 2H); 6.08 (s, IH); 3.55-3.50 (m, 2H); 3.20-3.16 (m, ^' lH); 2.98-2.95 (m, 2H); 2.77-2.7 '4 (m, 2H); 2.63 (s, 3H); 2.40-2.36 (m, IH); 2.27-2.22 (m, 2H); 1.75-1.62 (m, 9H); 1 .27- 1.24 (m, IH); 1.16-1.13 (m, I H).

Ex 1.82: N-Morpholin-4-yl-2-[l-(toluene-2-sulfonyl)-piperidin-3-yl]-a cetamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.90-7.78 (m, IH); 7.47-7.43 (m, IH); 7.32-7.28 (m, 2ϊI); 6.66 (s, IH); 3.83-3.81 (m, 2H); 3.54-3.44 (m, IH); 3.27-3.26 (m, IH); 3.19-3.1 1 (m, IH); 3.07-3.02 (m, 2H); 2.65 (s, 3H); 2.46-2.40 (m, IH); 2.36-2.31 (m, IH); 2.24- 2.15 (m, IH); 2.04-2.00 (m, 6H); 1.75-1.73 (m, IH); 1.59-1.55 (m, IH); 0.96-0.93 (m, IH).

Ex 1.83: N-Moφholin-4-yl-2-[l-(naphthalene-2-sulfonyl)-piperidin-3-y l]-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.31 (d, J = 14 Hz, IH); 7.98-7.91 (m, 3H); 7.76-7.19 (m, IH); 7.02-7.60 (m, 2H); 6.13 (s, IH); 3.85-3.83 (m, 2H); 3.78-3.60(m, IH); 3.49- 3.4 l(m, IH); 3.23-3.19 (m, IH); 3.02-2.88 (m, 4H); 2.73-2.71(m, IH); 2.56-2.48 (m, IH); 2.39-2.34 (m, 2H); 2.06-2.02 (m, IH); 1.76-1.73 (m, IH); 1.64-1.54 (m, 2H); 1.26-1.24 (m, IH); 1.08-1.06 (m, IH).

Ex 1.84: 2-[l-(iVaphthalene-2-sulfonyl)-piperidin-3-yl]-N-piperidin-l -yl-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.31 (d, J = 14 Hz, IH); 7.99-7.91 (m, 3H); 7.73-7.05 (m, IH); 7.66-7.61 (m, 2H); 6.08 (s, IH); 3.56-3.48 (m, IH); 3.28-3.10(m, IH); 3.01- 2.95 (m, 2H); 2.76-2.73 (m, 2H); 2.68-2.5 (m, IH); 2.43-2.31 (m, 2H); 2.31-2.09 (m, 2H); 2.1-1.9(m, IH); 1.82-1.76 (m, 3H); 1.66-1.63 (m, 3H); 1.4-1.36 (m, IH); 1.29- 1.19 (m, IH); 1.10-0.92 (m, IH). Ex 1.85: N-Azepan-l-yl-2-[l-(naphthalene-2-sulfonyl)-piperidin-3-yl]- acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.31 (d, J = 14 Hz, IH); 7.99-7.91 (m, 3H); 7.77-7.70 (m, IH); 7.66-7.59 (m, 2H); 6.46 (bs, IH); 3.59-3.5 l(m, IH); 3.12-3.10 (m, 3H); 2.77- 2.76 (m, IH); 2.63-2.58 (m, IH); 2.48-2.36 (m, IH); 2.34-2.30 (m, IH); 2.27-2.22 (m, I H); 1.96 1.66 (m, 12H); 1.38-1.28 (m, IH); l .l -0.9(m, IH). I vx 1.X6: yV-(l lexahydro-cyclopenta|c|pyrrol-2-yl)-2-[l-(naphthalcne-2-sulf onyl)- piperidin Vylj-ncetnmide

III NMR: (CDCl ₃ , 400 MHz) δ 8.32 (d, J- 16.8 H-/, I H); 7.99-7.91 (in, 3H); 7.77-7.70 (m, IH); 7.66-7.59 (m, 2H); 5.83 (s, IH); 3.62-3.54 (m, IH); 3.30-3.28 (m, IH); 3.07-

2.95 (m, IH); 2.95-2.91 (m, IH); 2.6-2.54 (m, 2H); 2.47-2.42 (m, 2H); 2.21 -2.17(m, IH); 1.76-1.60 (m, 10H); 1.6-1.32 (m, 2H); 1.132-1.13 (m, IH); 1.10-0.96 (m, IH). Ex 1.87: N-(3-Methyl-piperidin-l-yl)-2-[l-(naphthalene-2-sulfonyl)-pi peridin-3-yl]- acetamide-piperidin- 1 -yl-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.31 (d, J = 14 Hz, I H); 7.99-7.91 (m, 3H); 7.77-7.70 (m, IH); 7.67-7.61 (m, 2H); 6.08 (s, IH); 3.56 (m, IH), 3.01-2.95 (m, 3H); 2.61-2.58 (m, IH); 2.44-2.36 (m, 3H); 2.34-2.32 (m, IH); 2.31-2.30 (m, IH); 1.95-1.76 (m, IH); 1.76-1.62 (m, 5H); 1.27-1.23 (m, 2H); 1.19-0.92 (m, IH); 0.90-0.76 (m, 4H). Ex 1.88: 2-[l -(Naphthalene- l-sulfonyl)-piperidin-3-yl]-N-piperidin-l -yl-acetamide IH νMR: (CDCl ₃ , 400 MHz) δ 8.72 (t, J = 8.8 Hz, IH); 8.21 (d, J= 7.6 Hz, IH); 8.06 (d, J = 7.2 Hz, IH); 7.94-7.91(m, IH); 7.66-7.52 (m, 3H); 6.07(s, IH); 3.64-3.57 (m, IH); 3.02-2.95 (m, IH); 2.80-2.75 (m, 2H); 2.59-2.54 (m, IH); 2.36-2.34(m, IH); 2.30-

2.49 (m, 2H); 2.20-2.10 (m, IH); 1.99-1.91 (m, 4H); 178-1.61 (m, 6H); 1.414 (s, IH); 1.32-1.30 (m, IH). Ex 1.89: N-Moφholin-4-yl-2-[l-(naphthalene-l-sulfonyl)-piperidin-3-y l]-acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 8.70 (t, J= 8.8 Hz, IH); 8.21 (d, J= 7.6 Hz, IH); 8.06 (d, J = 8.4 Hz, IH); 7.94-7.91(m, IH); 7.68-7.52 (m, 3H); 6.12 (s, IH); 3.87-3.84 (m, 3H); 3.57-3.53 (m, 2H); 3.1-3.07 (m, IH), 2.87-2.84 (m, 3H), 2.69-2.64 (m, IH), 2.58-

2.50 (m, IH); 2.44-2.43 (m, IH), 2.36-2.30 (m, IH), 2.02-1.98 (m, IH), 1.74-1.71 (m, 2H), 1.56-1.54 (m, 2H), 1.0-1.19 (m, IH).

Ex 1.90: N-Azepan-l-yl-2-[l-(4-isopropyl-benzenesulfonyl)-piperidin-3 -yl]-acetamide IH νMR: (CDCl ₃ , 400 MHz) δ 9.08 (s, IH); 7.61 (dd, J= 2.8, 8.4 Hz, 2H); 7.49 (dd, J = 1.6, 8.4 Hz, 2H); 3.44-3.41 (m, 2H), 3.0-2.98 (m, IH), 2.89-2.86 (m, 3H), 2.8-2.6(m, IH), 2.31-2.25 (m, 2H), 2.01-2.05(m, IH), 1.89-1.86 (m, 2H), 1.63-1.45 (m, 12H), 1.44-1.21 (m, 6H).

Ex 1.91 : N-(Hexahydro-cyclopenta[c]pyrrol-2-yl)-2-[l-(4-isopropyl-ben zenesulfonyl)- piperidin-3 -yl] -acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 7.68-7.62 (m, 2H); 7.35 (d, J = 8.4 Hz, 2H); 5.83 (s, IH); 3.53-3.48 (m, 2H); 3.46-3.29 (m, IH); 3.07-2.88 (m, 3H); 2.67-2.55(m, 2H), 2.55- 2.48 (m, 2H), 2.46-2.39 (m, IH), 2.27-2.18 (m, IH), 1.84-1.72 (m, 3H), 1.63-1.5 (m, 2H); 1.48-1.23 (m, 4H); 1.25-1.1 (m, 2H); 1.1-0.9 (m, 6H); 0.87-0.76 (m, IH). Ex 1.92: l-Benzenesulfonyl-piperidine-3-carboxylic acid azocan-1 -yiamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.78-7.72 (m, 2H); 7.59-7.50 (m, 3H); 6.5 (s, I H);

3.51-3.49 (m, IH); 3.48-3.41(m, IH); 3.03-3.02 (m, IH); 2.85-2.81 (m, 3H); 2.59-2.51

(m, IH); 2.44-2.40 (m, 2H); 2.38-2.37 (m, 2H); 1.78-1.71 (m, 12H); 1.15-0.9 (m, I H);

0.9-0.85 (m,lH). Ex 1.93: 2-[l-(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-7V-piper idin-1 -yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.98-7.94 (m, IH); 7.53-7.51 (m, IH); 7.38-7.46 (m,

IH); 5.3 (s, IH); 3.66-3.59 (m, IH); 3.32-3.27 (m, IH); 3.08-2.99 (m, IH); 2.95-2.88 (m, IH); 2.74-2.66 (m, 2H); 2.39-2.38 (m, IH); 2.29-2.47 (m, IH); 2.15-2.11 (m, IH); 1.88-1.84 (m, IH); 1.76-1.69 (m, 4H); 1.67-1.62 (m, 5H); 1.42-1.41 (m, IH); 1.25-1.13 (m, IH).

Ex 1.94: 2-[l-(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-morpho lin-4-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.99-7.93 (m, IH); 7.53-7.52 (m, IH); 7.38-7.35 (m, IH); 6.15 (s, IH); 3.83-3.81 (m, 3H); 3.62-3.53 (m, IH); 3.26-3.14 (m, IH); 2.99-2.97 (m, IH); 2.82-2.79 (m, IH); 2.78-2.73 (m, 4H); 2.52 (m, IH), 2.54-2.48 (m, IH); 2.47- 2.43 (m, IH); 2.41-2.30 (m, IH); 2.06-2.01 (m, IH); 1.77-1.74 (m, IH); 1.73-1.71 (m, IH), 1.63-1.60 (m IH).

Ex 1.95: 2-[l-(4-Isopropyl-benzenesulfonyl)-piperidin-3-yl]-iV-(3-met hyl-piperidin-l- yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.68-7.62 (m, 2H); 7.36 (d, J= 8 Hz, 2H); 6.1 (s, IH); 3.51-3.46 (m, 5H); 3.01-2.95 (m, 3H); 2.38-2.32 (m, 2H); 2.18-2.17 (m, IH); 1.75-1.69 (m, 5H); 1.28 (d, J= 6.8 Hz, 6H); 1.28-1.27 (m, 2H), 0.91-0.85 (m, 6H). Ex 1.96: 2-[l-(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-(3-met hyl-piperidin-l- yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.00-7.94 (m, IH); 7.53-7.51 (m, IH), 7.36 (d, J= 8.8 Hz, IH); 6.02 (s, IH); 3.65-3.59 (m, IH); 3.31-3.27 (m, IH); 3.09-3.06 (m, IH); 2.94- 2.88 (m, 2H); 2.71-2.66 (m, IH); 2.39-2.37 (in, IH); 2.28-2.25 (m, IH); 2.15-2.12 (m, IH); 2.03-1.99 ( m, IH); 1.77-1.72 (m, 5H); 1.69-1.62 (m, 2H); 1.58-1.55 (m, IH); 1.18-1.15 (m, IH); 0.89-0.87 (m, 4H).

Ex 1.97: 2-[l-(2,4-Dichloro-benzenesulfonyl)-piperidin-3-yl]-jY-(hexa hydro-cyclopentii [c]pyrrol-2-yl)-acetamide

IH NMR: (DMSO-^ ₆ , 400 MHz) δ 8.15 (s, IH); 7.94-7.90 (m, 2H); 7.65-7.63 (m, I H);

3.56-3.53 (m, 2H); 2.96-2.88 (m, 2H); 2.77-2.72 (m, IH); 2.49-2.48 (m, 3H); 2.24-2.21

(m, IH); 1.88-1.86 (m, 2H); 1.68-1.59 (m, 8H); 1.46-1.37 (m, 3H); 1.07-1.03 (m, I H).

Ex 1.98: 7V-Azepan-l-yl-2-[l-(2,4-dichloro-benzenesulfonyl)-piperidin -3-yl]-acetamide IH NMR: (DMSO-Cf ₆ , 400 MHz) δ 8.0-7.97 (m, IH); 7.54 (d, J = 1 .6 Hz, I H); 7.36

(dd, J= 1.2, 8.4 HZ, IH), 6.44 (s, IH); 3.65-3.62 (m, 2H); 3.38-3.31 (m, IH); 3.25-3.24

(m, IH); 3.00-2.96 (m, 3H); 2.90-2.88 (m, 2H); 2.43-2.41 (m, IH); 2.27-2.24 (m, I H);

2.03-2.01 (m, IH); 1.88-1.84 (m, IH); 1.67-1.63 (m, 8H); 1.37-1.32 (m, 2H).

Ex. 1.99: 7V-Mθφholin-4-yl-2-[l-(2,4,6-trimethyl-benzenesulfonyl)-pi peridin-3-yl]- acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 6.93 (s, 2H); 6.08 (s, IH); 3.81-3.78 (m, 3H); 3.51-3.30

(m, 2H); 2.99-2.81 (m, 5H); 2.63 (s, 6H); 2.36-2.19 (m, 6H); 1.84 (s, 3H); 1.37-1.16

(m, 3H).

Ex. 1.100: N-Piperidin-l-yl-2-[l-(2,4,6-trimethyl-benzenesulfonyl)-pipe ridin-3-yl]- acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 6.93 (s, 2H); 6.06 (s, IH); 3.53-3.42 (m, 2H), 3.07-2.85

(m, IH); 2.85-2.68 (m, 3H); 2.70 (s, 6H); 2.72-2.69 (m, IH); 2.49-2.38 (m, IH); 2.29

(s, 3H); 2.33-2.28 (m, IH); 2.18-2.06(m, 2H); 1.96-1.87 (m, 2H); 1.78-1.63 (m, 4H);

1.45-1.32 (m, IH); 1.30-1.19 (m, 2H); 1.16-0.96 (m, IH); 0.86-0.75 (m, IH). Ex. 1.101 : ( 1 -Benzenesulfonyl-piperidin-3-yl)-acetic acid JV-benzyl-hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.74-7.72 (m, IH); 7.58-7.52 (m, 5H); 7.37-7.28 (m,

4H); 3.63-3.27 (m, 2H); 3.25-3.05 (m, IH); 2.23-1.96 (m, 5H); 1.82-1.55 (m, 4H);

1.18-1.04 (m, IH).

Ex 1.102: [l-(Toluene-4-sulfonyl)-piperidin-3-yl]-acetic acid N-phenyl-hydrazide IH NMR: (CDCl ₃ , 300 MHz) δ 7.64-7.59 (m, 2H); 7.43 (s, IH); 7.33-7.22 (m, 3H);

6.96-6.79 (in, 5H); 6.14 (s, IH); 3.18-3.03 (in, 3H); 2.84-2.82 (in, IH); 2.64-2.52 (in

IH); 2.43(s, 3H); 2.41-2.30 (m, 111); 2.24-2.16 (m, 111); 1.71-1.65 (m, 211); 1.28-1.25

(m, IH).

Ex 1.103: [l-(Toluene-4-sulfonyl)-piperidin-3-yl]-acetic acid JV-(2,4-dichloro-phenyl)- hydrazide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.62 (d, J = 8.16 Hz, 2H); 7.50(s, IH); 7.34-7.29 (m,

3H); 7.16 (d, J= 8.61 Hz, IH); 6.90 (d, J= 8.71 Hz, IH); 6.48-6.45 (m, IH); 3.21-3.14

(m, IH); 3.01-2.86 (m, 3H); 2.68-2.53 (m, IH); 2.43 (s, 3H); 2.38-2.24 (m, I H); 2.20

(dd, J= 5.4, 14 Hz, IH); 1.65-1.53 (m, 3H); 1.36-1.25 (m, IH).

Ex 1.104: N-Piperidin-l-yl-2-[l-(toluene-4-sulfonyl)-piperidin-3-yl]-a cetamide IH NMR: (CDCl ₃ , 300 MHz) δ 7.65-7.59 (m, 2H); 7.3 l(d, J = 7.98 Hz, 2H); 6.07 (s, IH); 3.52-3.46 (m, IH); 3.18-3.05 (m, IH); 2.96-2.87 (m, I H); 2.82-2.68 (m, 2H);

2.55-2.49 (m, IH); 2.36 (s, 3H); 2.45-2.18 (m, 4H); 2.15-2.13 (m, IH); 1.81 -1.62 (m,

7H); 1.53-1.49 (m, IH); 1.37-1.33 (m, IH); 1.10-1.06 (m, IH).

Ex. 1.105: N-P)τrolidin-l-yl-2-[l-(toluene-4-sulfonyl)-piperidin-3-yl] -acetamide

IH NMR: (CDCl ₃ , 300 MHz) δ 7.65-7.59 (dd, J= 2.43, 8.34 Hz, 2H); 7.3 l(d, J= 7.98 Hz, 2H); 6.46(s, IH; 3.53-3.46 (m, 3H); 2.93-2.76 (m, 4H); 2.51-2.38 (m, 4H); 2.36 (s,

3H); 1.88-1.75 (m, 4H); 1.72-1.63 (m, 2H); 1.38-1.27 (m, IH); 1.16-1.06 (m, IH).

Ex. 1.106: [l-(Toluene-4-sulfonyl)-piperidin-3-yl] -acetic acid jV-cyclohexyl-hydrazide

IH NMR (CDCl ₃ , 300 MHz) δ 7.62 (d, J= 8.1 Hz, 2H); 7.32 (d, J= 8.1 Hz, 2H); 7.08

(s, IH); 3.49(s, IH); 3.24-3.19 (m, 2H); 1.86-2.80 (m, IH); 2.78-2.72 (2.75-2.58 (m, 2H), 2.43(3H, s), 2.33-2.20 (m, 2H); 2.07-2.03 (m, IH); 1.88-1.82 (m, 2H); 1.80-1.68

(m, 4H); 1.66-1.48 (m, 4H); 1.28-1.09 (m, 6H).

Ex. 1.107: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid W-(4-chloro-phenyl)- hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.75-7.72 (m, 2H); 7.61-7.59 (m, IH); 7.55-7.51 (m, 3H); 7.25-7.19 (m, 2H); 6.821 (d, J = 8.8 Hz, 2H); 6.14 (d, J = 4 Hz, IH); 3.08-2.98

(m, 3H); 2.89-2.85 (m, IH); 2.54-2.48 (m, IH); 2.30-2,29 (m, IH); 2.20-2.16 (m, IH);

1.71-1.61 (m, 2H); 1.39-1.21 (m, IH).

Ex. 1.108: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid λMert-butyl-hydrazide

IH NMR: (CDCl ₃ , 40OvMHz) δ 7.77-7.73 (m, 2H); 7.61-7.51 (m, 3H); 6.98 (s, IH); 3.23-2.91 (m, 2H); 2.89-2.68 (m, IH); 2.67-2.57 (m, IH); 2.39-2.31 (m, IH); 2.29-2.18

(m, IH); 2.11-1.96 (m, IH); 1.77-1.73 (m, 3H); 1.72-1.60 (m, IH); 1.12 (s, 9H).

Ex. 1.109: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid iV-butyl-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.77-7.73 (m, 2H); 7.59-7.51 (m, 3H); 3.27-3.14 (m,

2H); 2.86-2.82 (m, 3H); 2.71-2.52 (m, IH); 2.28-2.22 (m, 3H); 2.06-2.02 (m, IH); 1.72-1.71 (m, 3H); 1.49-1.34 (m, 3H); 1.28-1.12 (m, IH); 0.94-0.90 (t, J= 7.2 Hz, 3H).

Ex. 1.110: 2-(l -Benzenesulfonyl-piperidin-3-yl)-N-(hexahydro-cyclopenta[c]p yiTol-2- yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.78-7.71 (m, 2H); 7.60-7.50 (m, 3H); 5.83 (s, I H);

3.59-3.47 (m, IH); 3.31-3.28 (m, IH); 2.94-2.88 (m, IH); 2.54-2.32 (m, 8H); 2.30-2.29

(m, IH); 2.27-2.13 (m, IH); 1.79-1.54 (m, 9H); 1.12-0.98 (m, I H).

Ex. 1.111 : [l -β-Chloro^-methyl-benzenesulfony^-piperidin-S-yll-acetic acid λMert- butyl-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.81 (d, J = 7.2 Hz, IH); 7.57 (dd, J = 0.8, 8 HZ, I H);

7.23 (d, J = 8.8 Hz, IH); 6.95(s, IH); 3.49-3.31 (m, 2H); 3.08-2.86 (m, I H); 2.85-2.65

(m, IH); 2.42 (s, 3H); 2.33-2.28 (m, IH); 2.19-2.17 (m, IH); 2.09-2.04 (m, I H); 1.78-

1.72 (m, 3H); 1.5-1.2 (m, IH); 1.12 (s, 9H). Ex. 1.1 12: [l-(3-Chloro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-aceti c acid N- butyl-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.83 (dd, J= 7.6, 8.8 Hz, IH); 7.57 (d, J= 7.6 Hz, IH);

7.24-7.22 (m, IH); 7.08 (s, IH); 3.45-3.31 (m, 2H); 3.09-3.04 (m, IH); 2.84-2.79 (m,

3H); 2.66 (s, 3H); 2.26-2.17 (m, 2H); 2.03-1.99 (m, IH); 1.81-1.72 (m, 2H); 1.59-1.48 (m, IH); 1.45-1.38 (m, 2H); 1.35-1.21 (m, 3H); 1.00-0.78 (m, 4H).

Ex. 1.1 13: 2-[l-(4-Isopropyl-benzenesulfonyl)-piperidin-3-yl]-N-piperid in-l-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.68-7.62 (m, 2H); 7.33 (d, J= 8 Hz, 2H); 6.09 (s, IH);

3.52-3.50 (m, 2H); 3.01-2.91 (m, 3H); 2.82-2.62 (m, 2H); 2.52-2.18 (m, 5H); 2.06-1.99 (m, IH); 1.83-1.58 (m, 7H); 1.51-1.35 (m, IH); 1.10(d, J = 7.2 Hz, 6H); 1.10-0.92 (m,

IH).

Ex. 1.114: 2-[l-(4-Isopropyl-benzenesulfonyl)-piperidin-3-yl]-N-morphol in-4-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.67-7.62 (m, 2H); 7.36 (d, J = 7.2 Hz, 2H); 6.11 (s, IH); 3.84-3.79 (m, 3H); 3.76-3.70 (m, IH); 3.39-3.21 (m, 2H); 3.00-2.82 (m, 5H);

2.65-2.27 (m, 5H); 2.06-1.76 (m, IH); 1.74-1.61 (m, 2H); 1.10 (d, J = 7.2 Hz, 6H);

1.08-0.91 (m, IH).

Ex. 1.115: (l-Benzenesulfonyl-piperidin-3-yl)-acetic acid vV-(3-nitro-phenyl)- hydrazide IH NMR: (CDCl ₃ , 400 MHz) δ 7.78-7.68 (m, 5H); 7.63-7.51 (m, 3H); 7.37 (t, J = 8.4

Hz, IH); 7.17 (dd, J= 1.2, 8 Hz, IH); 6.40 (d, J= 2.8 Hz IH); 3.19-3.18 (m, IH); 3.03-

2.88 (m, 3H); 2.63-2.58 (m, IH); 2.4-2.33 (m, IH); 2.26-2.21 (m, IH); 1.82-1.78 (m,

IH); 1.71-1.53 (m, 2H); 1.41-1.37 (m, IH)

Ex. 1.116: N-Azepan-l-yl-2-[l-(4-fluoro-benzenesulfonyl)-piperidin-3-yl ]-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.73 (m, 2H); 7.23-7.18 (m, 2H); 6.49(s, I H),

3.54-3.44 (m, I H); 3.12-3.10(m, IH); 3.04-2.98 (m, 2H); 2.80-2.76(m, I H); 2.54-2.20

(m, 4H); 2.03-1.80 (m, 3H); 1.79-1.56 (m, 9H); 1.26-1.23 (m, I H); 1.15-0.97(m, IH). Ex. 1.1 17: 2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yI]-N-(hexahydro -cyclopenta

[c] pyrrol-2-yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.74 (m, 2H); 7.22-7.18 (m, 2H); 5.83 (s, IH);

3.55-3.46 (m, 211); 3.09-2.86 (m, IH); 2.80-2.61 (m, IH); 2.55-2.43 (m, 3H); 2.41-2.26

(m, 4H); 2.25-2.18 (m, IH); 1.84-1.71 (m, 3H); 1.69- 1.60 (m, 4H); 1.51-1.25 (m, 3H); 1.43-1.18 (m, IH).

Ex 1.1 18: 2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-(4-methyl- piperidin-l- yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.72 (m, 2H); 7.22-7.18 (m, 2H); 6.1 (s, IH);

3.54-3.44 (m, IH); 3.21-3.07(m, IH); 3.02-2.82 (m, 2H); 2.61-2.42(m, IH); 2.44-2.28 (m, 4H); 2.21-2.10 (m, IH); 1.77-1.72 (m, 2H); 1.68-1.60 (m, 4H); 1.34-1.24 (m, 3H);

1.12-0.98 (m, IH); 0.96-0.81 (d, J= 6.2 Hz, 3H).

Ex. 1.119: 2-[l-(4-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-(3-methyl- piperidin-l- yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.73 (m, 2H); 7.22-7.18 (m, 2H); 6.01 (s, IH); 3.52-3.50 (m, 2H); 3.09-2.99 (m, 3H); 2.65-2.48 (m, IH); 2.41-2.25 (m, 2H); 2.19-2.16

(m, 2H); 2.15-1.98 (m, IH); 1.95-1.68 (m, IH); 1.78-1.57 (m, 5H); 1.41-1.20 (m, IH);

1.18-0.98 (m, IH); 0.95-0.78 (m, 4H).

The following compounds were prepared following the general scheme-2 Example 2.1:

Z-fl^jS-Dichloro-benzenesuIfonyO-piperidin-S-yll-iV-piper idin-l-yl-acetamide

Step A: [l-(2, 3-Dichloro-benzenesulfonyl)-pipeήdin-3-yl]-methanol

3-piperidine methanol (3.0g, 26.05 mmol, 1 equiv.) was dissolved in dry dichloromethane (30 mL) in a round bottomed flask equipped with N ₂ balloon. Triethyl amine (2.63g, 3.65 mL, 26.05 mmol, lequiv.) was added to the solution and stirred for 20-30 minutes at room temperature. After stirring for about 20-30 minutes, 2,3- dichlorobenzene sulfonyl chloride (6.71 g, 27.35 mmol, 1.05 equiv.) was added to the reaction mixture at 0 ⁰ C to 5 ⁰ C. Then the reaction mixture was stirred at room

temperature and monitored by TLC till completion of the reaction. The reaction mixture was diluted with dichloromethane and cold water and further stirred. The layers were separated and the organic layer was washed with the water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to get crude product. The crude product was purified by column chromatography using 3:7 ethyl acetate: pet. ether as mobile phase to get pure product (7.9g, 23.97 mmol, 91%). IH NMR (DMSO-J ₆ , 400 MHz) δ 7.94 (m, 2H); 7.56 (t, J= 8 Hz, I H); 4.55 (t, J = 5.2 Hz, I H); 3.72 (dd, J = 3.6, 12.4 Hz, IH); 3.60 (d, J = 12.4 Hz, IH); 3.32-3.27 (m, IH); 3.17-3.13 (m, IH); 2.77-2.70 (m, IH); 2.51-2.46 (m, IH); 1.69-1.58 (m, 3H); 1.42-1.38 (m, IH); 1.07-1.02 (m, IH).

Step B: [l-(2, S-Dichloro-benzenesulfonylJ-piperidinS-ylJ-acetonitrile Triethyl amine (2.78g, 3.83 mL, 27.57 mmol, 1.15 equiv) was added to the solution of the alcohol obtained above (7.9g, 23.97 mmol, 1 equiv) in dry dichloromethane (60 mL) in a round bottomed flask equipped with CaCl ₂ guard tube at room temperature. Methane sulfonyl chloride (3.02 g, 2.0 mL, 26.36 mmol, 1.1 equiv.) was added to the above reaction mixture at 0-5 ⁰ C. The reaction mixture was stirred at room temperature and monitored by TLC till completion. The reaction mixture was diluted with dichloromethane, washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated in vacuo to yield the mesylate derivative, which was used without further purification.

IH NMR: (DMSO-J ₆ , 400 MHz) δ 7.97-7.94 (m, 2H); 7.57 (t, J= 6 Hz, IH); 4.14-4.02 (m, 2H); 3.68-3.66 (m, IH); 3.56-3.53 (m, lH);θ.l5 (s, 3H); 2.84 (t, J= 10.8 Hz, IH); 2.72 (t, J = 2, 10 Hz, IH); 1.95-1.91 (m, IH); 1.71-1.69 (m, 2H); 1.44-1.42 (m, IH); 1.21-1.19 (m, IH). The mesylate derivative obtained above (0.5g, 1.25 mmol, 1 equiv.) was dissolved in dry dimethyl formamide (5 mL) in a round-bottomed flask equipped with N ₂ balloon. 18-Crown-6 ether (0.05g, 0.01 w/w) was added to the reaction mixture followed by portion wise addition of NaCN (0.092 g, 1.87 mmol, 1.5 equiv.). The reaction was stirred at room temperature for 16h. Then, the reaction mixture was diluted with cold water and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over sodium sulphate and concentrated in vacuo to furnish crude nitrile derivative. The crude material was purified by column chromatography to obtain pure white solid (0.25 g, 0.753 mmol, 60%).

IH NMR: (DMSO-^ ₆ , 400 MHz) δ 7.96 (m, 2H); 7.58 (t, J=6 Hz, I H); 3.68 (dd, J =12, 3.6 Hz, IH); 3.56 (dd, J= 12.4, 3.6 Hz, I H); 2.84-2.77 (m, I H); 2.63 (dd, J = 12. 2 Hz, IH); 2.54-2.46 (m, 2H); 1.97-1.72 (m, 2H); 1.69-1.67 (m, I H); 1.46-1.44 (m, I H); 1.27-1.23 (m, IH). Step C: [1 -(2, 3-Dichloro-benzenesulfonyl)-piperidin-3-yl] -acetic acid, methyl ester

Anhydrous hydrochloride gas was passed through two necked round bottomed flask equipped with condenser and CaCl ₂ guard tube containing the nitrile derivative obtained above(6g, 18.07 mmol, 1 equiv.) in dry methanol (70 mL) for 1.5h. The solvent was removed in vacuo to get solid residue. Water was added to this residue and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain the desired ester (3.3 g, 9.315 mmol, 45%).

IH NMR: (CDCl ₃ , 400 MHz) δ 8.01 (dd, J = 1.6, 8 Hz, IH); 7.66 (dd, J - 0.8, 8 HZ, IH); 7.31 (t, J = 8 Hz, IH); 3.72-3.60 (m, 2H); 3.69 (s, 3H); 2.98-2.94 (m, IH); 2.72- 2.67(m, IH); 2.33-2.09 (m, 3H); 1.84-1.82 (m, IH); 1.73-1.70 (m, IH); 1.64-1.59 (m, IH); 1.26-1.16 (m, IH).

Step D: [1 -(2, 3-Dichloro-benzenesulfonyl)-piperidin-3-yl] -acetic acid Potassium hydroxide (1.56g, 27.87 mmol, 3 equiv.) in water was added to the stirring solution of ester as obtained above (3.3g, 9.04 mmol, 1 equiv.) in methanol (20 mL) at room temperature. The reaction was stirred for 2-4h. at room temperature. The solvent was removed in vacuo to obtain residue, diluted with water and washed with ethyl acetate to remove organic impurities. The aqueous layer was separated and cooled to 0 ⁰ C, acidified with HCl (0.1 N). The separated solid was filtered off, dried in air to constant weight (2.5g, 7.12 mmol, 79%). IH NMR: (DMSO-^, 400 MHz) δ 12.13 (s, IH); 7.94 (dd, J - 1.2, 2.8 Hz, 2H); 7.69 (t, J = 8 Hz, IH); 3.62 (dd, J = 3.6, 12 Hz, IH); 3.52 (d, J = 12.8 Hz, IH); 2.86-2.80 (m, IH); 2.63-2.58 (m, IH); 2.21-2.08 (m, 2H); 1.89-1.84 (m, IH); 1.72-1.66 (m, 2H); 1.54-1.48 (m, IH); 1.21-1.13 (m, IH). Step F: 2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-piperi din-l-yl- acetamide

To mixture of the acid derivative obtained above (0.5g, 1.42 mmol, 1 equiv.) DMAP (0.174 g, 1.42 mmol, 1 equiv.) and dry dichloromethane (10 mL) in a round bottomed flask was added EDCI (0.654 g, 3.42 mmol, 2.4 equiv.) under nitrogen atmosphere,

followed by 1 -aminopiperidine (0.174g, 0.18 mL, 1.56 mmol, 1.1 equiv.) at 0 ⁰ C to 5

⁰ C. The reaction mixture was brought to the room temperature and stirred for 16h. Then the reaction mixture was diluted with dichloromethane. The organic layer washed with water, brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The compound was purified by column chromatography using (0.7:99.3) methanol xhloroform as eluent to furnish the desired product (0.420 g, 0.967 mmol,

68%).

IH NMR: (DMSO-d ₆ , 400 MHz) δ 8.73 (bs, IH); 7.92-7.96 (m, 2H); 7.56 (t, J = 8.4

Hz, IH); 3.58-3.54 (m, 2H); 2.82-2.75 (m, 2H); 2.61-2.52 (m, 3H); 2.24-2.20 (m, IH); 1.88 - 1.83 (m, 2H); 1.67-1.65 (m, 2H); 1.53-1.25 (m, 8H); 1.06 - 1.03 (m, IH).

The following compounds were prepared in a similar way as described in example 2.1 with suitable variations as are within the scope of the person skilled in art.

Ex 2.2: 2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-7V-moφh olin-4-yl- acetamide IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.90 (bs, IH); 7.96-7.92 (m, 2H); 7.56 (t, J = 8.4

Hz, IH); 3.59-3.57 (m, 4H); 3.36-3.29 (m, 2H); 2.82-2.77 (m, IH); 2.68-2.66 (m, 5H);

2.28 - 2.25 (m, IH); 1.89-1.83 (m, 2H); 1.68-1.65 (m, 2H); 1.44 - 1.39 (m, IH); 1.12-

1.10 (m, IH).

Ex. 2.3: [l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid _J /V-(2,4-dichloro- phenyl)-hydrazide

IH NMR: (DMSO-J ₆ , 400 MHz) δ 9.83 (s, IH); 7.96-7.93 (m, 2H); 7.62 (s, IH); 7.58

(t, J= 8.4 Hz, IH); 7.40 (d, J = 2.4 Hz, IH); 7.40 (dd, J= 2.4, 8.8 Hz, IH); 6.69 (d, J=

8.8 Hz, IH); 3.54-3.51 (m, I H); 3.42-3.39 (m, IH); 2.82 - 2.76 (m, 111); 2.68-2.66 (m,

IH); 2.14-2.12 (m, 2H); 1.98-1.92 (m, IH); 1.75-1.71 (m, 2H); 1.51-1.44 (m, IH); 1.12-1.10 (m, IH).

Ex. 2.4: ' 2-[l-(2,5-Dichloro-benzenesulfonyl)-piperidin-3-yl]-iV-piper idin-l-yl- acetamide

IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.04 (dd, J= 1.2, 16.4 Hz, IH); 7.42 (dd, J= 1.2,

5.6 Hz, 2H); 6.08 (s, IH); 3.69-3.62 (m, IH); 3.46-3.37 (m, IH); 3.29-3.27 (m, IH); 2.96-2.88 (m, IH); 2.77-2.70 (m, 2H); 2.41-2.39 (m, IH); 2.28-2.26 (m, 2H); 2.15-2.14

(m, IH); 1.86-1.84 (m, IH); 1.78-1.74 (m, 3H); 1.66-1.62 (m, 3H); 1.43-1.41(m, 2H);

1.20-1.16 (m, 2H).

Ex. 2.5: 2-[l-(2,5-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-morpho lin-4-yl- acetamide

IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.02 (dd, J = 1.2, 16 Hz, 1 H); 7.43 (dd, J = 1.6, 5.2

Hz, 2H); 6.14 (bs, IH); 3.84-3.82 (m, 2H); 3.63-3.55 (m, I H); 3.29-3.23 (m, I H); 3.17- 5 3.15 (m, IH); 3.09-2.95 (m, IH); 2.88-2.78 (m, 3H); 2.51-2.49 (m, I H); 2.41-2.39 (m,

IH); 2.20-2.18 (m, IH); 2.07-2.06 (m, IH); 1.78-1.71 (m, IH); 1.63-1.54 (m, 3H);

1.47-1.45 (m, IH); 1.20-1.24 (m, IH).

Ex. 2.6: N-Piperidin-l-yl-2-[l-(2,4,6-trichloro-benzenesulfonyl)-pipe ridin-3-yl]- acetamide 10 IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.73 (bs, IH); 7.89 (d, J = 2.4 Hz, 2H); 3.64-3.28

(m, 2H); 2.87-2.84 (m, IH); 2.65-2.57 (m, 4H); 2.24-2.20 (m, IH); 1.88-1.83 (m, 2H);

1.68-1.65 (m, 2H); 1.53-1.48 (m, 4H); 1.44-1.43 (m, 2H); 1.31-1.30 (m, IH); 1.28-

1.25(m, IH); 1.05-0.98 (m, IH).

Ex. 2.7: N-Moφholin-4-yl-2-[l-(2,4,6-trichloro-benzenesulfonyl)-pipe ridin-3-yl]- 15 acetamide

IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.90 (bs, IH); 7.89 (d, J = 3.2 Hz, 2H); 3.63-3.58 (m, 6H); 2.88-2.83 (m, IH); 2.71-2.56 (m, 4H); 2.31-2.25 (m, IH); 1.89-1.88 (m, 3H);

1.68-1.65 (m, 2H); 1.41-1.39 (m, IH); 1.14-1.07 (m, IH).

Ex. 2.8: N-Azepan-l-yl-2-[l-(2,3-dichloro-benzenesulfonyl)-piperidin- 3-yl]-acetamide 20 IH NMR: (DMSO-J ₆ , 400 MHz) δ 9.03 (bs, IH); 7.96-7.92 (m, 2H); 7.58-7.54 (m, IH); 3.58-3.55 (m, 2H); 2.87-2.71 (m, 5H); 2.62-2.48 (m, IH); 2.28-2.23 (m, IH); 1.91-1.82 (m, 2H); 1.67-1.64 (m, 2H); 1.55-1.41 (m, 9H); 1.10-1.03 (m, IH). Ex. 2.9: 2-[ 1 -(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-(octahydro -pentalen-2- yl)-acetamide

25 IH NMR: (CDCl ₃ , 400 MHz) δ 8.01 (dd, J= 1.6, 8 Hz, IH); 7.66-7.63 (m, IH); 7.34- 7.25 (m, IH); 5.81 (bs, IH); 3.68-3.64 (m, 2H); 3.29-3.27 (m, 2H); 2.95-2.93 (m, IH); 2.74-2.68 (m, 2H); 2.55-2.53 (m, 2H); 2.40 (d, J = 6.8 Hz, 2H); 2.26-2.24 (m, IH); 2.11-2.09 (m, IH); 2.05-2.03 (m, IH); 1.86-1.84 (m, IH); 1.76-1.70 (m, 3H); 1.49-1.41 (m, 3H); 1.25-1.19 (m, IH); 0.92-0.85 (m, IH).

M) Ex 2.10: 2-f 1 -(2,3-Dichloro-bcn7.cncsuironyl)-pipcridin-3-yl]-N-(4-methyl -piperidin-l- yl)-acetamide

IH NMR: (DMSO-J ₆ , 400 MHz) δ 8.70 (bs, IH); 7.96-7.92 (m, 2H); 7.58-7.54 (m, IH); 3.58-3.53 (m, 2H); 2.80-2.75 (m, 3H); 2.60-2.37 (m, 2H); 2.24-2.20 (m, IH);

1.89-1.83 (m, 2H); 1.67-1.54 (m, 4H); 1.43-1.38(m, I H); 1.32-1.29 (m, 5H); 0.97-0.89

(m, 3H).

Ex. 2.11 : 2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-(3-met hyl-piperidin-l- yl)-acetamide IH NMR: (DMSCW ₆ , 400 MHz) δ 8.72 (bs, IH); 7.95-7.92 (m, 2H); 7.58-7.54 (t, J = 8

Hz, IH); 3.60-3.57 (m, 2H); 2.79-2.77 (m, 3H); 2.35 (t, J = 5.6 Hz, IH); 2.24-2.21 (m,

2H); 2.09 (t, J= 5.6 Hz, IH); 1.88-1.83 (m, 2H); 1.67-1.48 (m, 5H); 1.44-1.41 (m, 2H);

1.23-1.21 (m, 2H); 0.92-0.75 (m, 3H).

Ex. 2.12: [1 -(2,3 -Dichloro-benzenesulfonyl)-piperidin-3-yl] -acetic acid 7V-(2-chloro- phenyl)-hydrazide

IH NMR: (DMSO-βfc, 400 MHz) δ 9.80 (s, IH); 7.95-7.92 (m, 2H); 7.56 (d, J = 8 Hz,

IH); 7.40 (s, IH); 7.25 (dd, J = 1.2, 7.6 Hz, IH); 7.14-7.10 (m, IH); 6.75 -6.71 (m,

2H); 3.68 (dd, J= 3.2, 12 Hz, IH); 3.55 (d, J= 12.4 Hz, IH); 2.83 (t, J= 11.6 Hz, IH);

2.63 (t, J= 12 Hz, IH); 2.14-2.12 (m, 2H); 1.96-1.95 (m, IH); 1.76-1.68 (m, 2H); 1.45- 1.42 (m, IH); 1.13-1.10 (m, IH).

Ex. 2.13: [l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-acetic acid jV-(4-chloro- phenyl)-hydrazide

IH NMR: (DMSO-^ ₅ , 400 MHz) δ 9.68 (s, IH); 7.96-7.89 (m, 3H); 7.56 (t, J= 8 Hz,

IH); 7.13 (d, J= 8.4 Hz, 2H); 6.67 (d, J= 8.4 Hz, 2H); 3.66 (d, J = 13.2 Hz, IH); 3.54 (d, J = 12 Hz, IH); 2.83 (t, J = 10.4 Hz, IH); 2.61 (t, J= 10.4 Hz, IH); 2.11-2.09 (m,

2H); 1.96-1.92 (m, IH); 1.73-1.66 (m, 2H); 1.45-1.42 (m, IH); 1.13-1.10 (m, IH).

Ex 2.14: 2-[l-(3-Chloro-4-methyl-benzenesulfonyl)-piperidin-3-yl]-N-p iperidin-l-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.73-7.54 (m, IH); 7.53-7.49 (m, IH); 7.37 (d, J = 8 Hz ₅ IH); 6.07 (s, IH); 3.52 -3.44 (m, 2H); 2.98-2.88 (m, 2H); 2.56-2.43 (m, 2H); 2.46

(s, 3H); 2.31-2.28 (m, IH); 2.03-2.00 (m, 2H); 1.79 (m, 2H); 1.76-1.70 (m, 7H); 1.33-

1.23 (m, IH); 1.20-1.14 (m, IH); 0.98-0.89 (m, IH).

Ex. 2.15: 2-[l-(3-Chloro-4-methyl-benzenesulfonyl)-piperidin-3-yl]-N-m orpholin-4-yl- acelamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.70 (dd, J = 1.2, 12.8 Hz, IH); 7.54-7.48 (m, IH);

7.37 (d, J-- 7.6 Hz, 111); 6.15 (s, 111); 3.84-3.82 (m, 3H); 3.42-3.39 (m, III); 3.36-3.33

(m, I H); 2.95-Z93 (m, IH); 2.89-2.8 (m, 4H); 2.68-2.63 (m, 2H); 2.54-2.49 (m, IH);

2.45 (s, 3H); 2.38- 2.36 (m IH); 2.33-2.28 (m, IH); 2.06-2.02 (m, 2H); 1.77-1.73 (m, IH); 1.67-1.62 (m. IH).

Ex. 2.16: 2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-/V-(hexahydr o-cyclopenta [c] pyrrol-2-yl)-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.07-8.04 (m, IH); 7.52-7.46 (m, 2H); 7.40-7.36 (m,

IH); 5.87 (s, IH); 3.67-3.64 (m, IH); 3.26-3.23 (m, IH); 2.94-2.89 (m, IH); 2.70-2.65

(m, 2H); 2.40-2.39 (m, 2H); 2.27 (m, 2H); 2.23-2.19 (m, IH); 2.14-2.22 (m, I H); 1.84-

1.83 (m, IH); 1.75-1.72 (m, 2H); 1.70-1.68 (m, 5H); 1.59-1.50 (m, 3H); 1.26 (m, IH).

Ex. 2.17: [l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl] -acetic acid 7V-(2-chloro- phenyl)-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.03 (dd, J = 1.2, 8 Hz, IH); 7.64 (s, IH); 7.53-7.50

(m, 2H); 7.48-7.46 (m, IH); 7.40-7.36 (m, IH); 7.29-7.25 (m, IH); 7.18-7.14 (m, IH);

6.94-6.91 (m, IH); 6.85-6.81 (m, IH); 6.49 (s, IH); 3.38-3.29 (m, 2H); 3.14-3.09 (m,

IH); 2.55-2.49 (m, IH); 2.29-2.26 (m, IH); 2.20-2.15 (m, IH); 1.62-1.58 (m, IH); 1.80-1.73 (m, 2H); 1.23 (m, IH).

Ex. 2.18: [l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl] -acetic acid W-(4-chloro- phenyl)-hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.02 (d, J= 8 Hz, IH); 7.64 (s, IH); 7.53-7.47 (m, 2H);

7.40-7.36 (m. IH); 7.24-7.17 (m, IH); 6.88-6.82 (m, 2H); 6.14 (s, IH); 3.41-3.32 (m, 2H); 3.18-3.10 (m, IH); 2.72-2.66 (m, IH); 2.28-2.19 (m, 2H); 1.78-1.76 (m, 2H);

1.58-1.55 (m, 2H); 1.47-1.43 (m, IH); 1.25-1.19 (m, IH).

Ex. 2.19: 2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-(3-methyl- piperidin-l-yl)- acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 8.06-8.00 (m, IH); 7.52-7.44 (m, 2H); 7.39-7.26 (m, 2H); 6.00 (s, IH); 3.66-3.61 (m, IH); 3.39-3.32 (m, IH); 3.26-3.23 (m, IH); 3.12-3.07

(m, IH); 2.94-2.88 (m, 2H); 2.72-2.67 (m, IH); 2.37-2.33 (m, IH); 2.31-2.28 (m, IH);

2.13 (m, IH); 2.08-2.01 (m, IH); 1.99-1.91 (m, 2H); 1.86-1:69 (m, 4H); 1.66-1.57 (m,

1 H); 0.84 (m, 4H).

Ex. 2.20: 2-[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-piperi din-l-yl- acetamide

IH νMR: (DMSO-*, 400 MHz) δ 8.73 (s, IH); 7.84-7.79 (m, IH); 7.62-7.56 (m, IH);

7.34-7.29 (m, IH); 3.54-3.45 (m, 2H); 2.87-2.71 (m, IH); 2.63-2.54 (m, 4H); 2.31-2.23

(m, 2H); 1.90-1.84 (m, 2H); 1.69-1.30 (m, 9H); 1.06-1.03 (m, IH).

Ex. 2.21 : 2-[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-morpho lin-4-yl- acetamide

IH NMR: (DMS0-<4 400 MHz) δ 8.90 (s, IH); 7.84-7.79 (m, I H); 7.61 -7.56 (m, 1 H);

7.33-7.29 (m, IH); 3.58-3.44 (m, 6H); 2.70-2.68 (m, 4H); 2.58-2.52 (m, I H); 2.32-2.27 (m, 2H); 1.89 (bs, 2H); 1.69-1.60 (m, 2H); 1.44-1.41 (m, I H); 1.04-0.99 (m, I H).

Ex. 2.22: 2-[l-(4-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-p iperidin-l-yl- acetamlde

IH NMR: (CDCl ₃ , 400 MHz) δ 7.95-7.84 (m, IH); 7.02-6.96 (m, 2H); 6.08 (s, IH);

3.57-3.48 (m, IH); 3.29-3.07 (m, IH); 2.97-2.88 (m, 2H); 2.79-2.73 (m, 2H); 2.61-2.57 (m, IH); 2.45 (s, 3H); 2.40-2.32 (m, 2H); 2.26-2.21 (m, 2H); 2.12-2.10 (m, IH); 2.00-

1.83 (m, IH); 1.77-1.68 (m, 5H); 1.58-1.52 (m, IH); 1.44-1.40 (m, IH); 1.15-1.1 1 (m,

IH).

Ex. 2.23: 2-[l-(4-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-m oφholin-4-yl- acetamide IH νMR: (CDCl ₃ , 400 MHz) δ 7.93-7.82 (m, IH); 7.02-6.96 (m, 2H); 6.13 (s, IH);

3.83-3.68 (m, 4H); 3.54-3.42 (m, IH); 3.22-3.11 (m, 2H); 3.0-2.95 (m, IH); 2.88-2.79

(m, 4H); 2.66-2.59 (m, IH); 2.46 (s, 3H); 2.44-2.38 (m, IH); 2.37-2.14 (m, IH); 2.04-

1.83 (m, IH); 1.77-1.72 (m, IH); 1.65-1.54 (m, IH); 1.39-1.12 (m, IH).

Ex. 2.24: 2-[l-(2,6-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-piperi din-l-yl- acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 7.52-7.47 (m, IH); 7.04-6.99 (m, 2H); 6.09 (s, IH);

3.71-3.64 (m, IH); 3.49-3.42 (m, IH); 3.21-3.11 (m, IH); 3.09-2.96 (m, IH); 2.84-2.75

(m, 2H); 2.67-2.614 (m, IH); 2.51-2.47 (m, III); 2.40-2.33 (m, IH); 2.30-2.19 (m, 2H);

1.88-1.59 (m, 8H); 1.53-1.41 (m, IH); 1.20-1.11 (m, IH). Ex. 2.25: 2-[l-(2,6-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-morpho lin-4-yl- acetamide

IH νMR: (DMS0-<4 400 MHz) δ 8.91 (s, IH); 7.77-7.74 (m, IH); 7.35-7.30 (m, 2H);

3.60-3.50 (m, 6H); 2.70-2.59 (m, 5H); 2.40-2.27 (m, 2H); 1.94-1.88 (m, 2H); 1.71-1.62 (m, 2H); 1.46-1.43 (m, IH); 1.07-1.01 (m, IH). Ex. 2.26: N-Azepan-l-yl-2-[l-(2,4-difluoro-benzenesulfonyl)-piperidin- 3-yl]-acetamide

IH νMR (CDCl ₃ , 400 MHz) δ 7.88-7.84 (m, IH); 7.01-6.92 (m, 2H); 6.43 (s, IH); 3.61-3.56 (m, 2H); 3.20-3.16 (m, IH); 3.05-2.98 (m, 3H); 2.79-2.75 (m, 2H); 2.56-2.37 (m, 2H); 2.28-2.13 (m, 2H); 1.83-1.61 (m, 10H); 1.17-1.10 (m, IH).

Ex. 2.27: 2-[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-iV-(hexa hydro- cyclopenta [c] pyrrol-2-yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.87-7.84 (m, IH); 7.00-6.92 (m. 2H); 5.84 (s, I H);

3.64-3.58 (m, 2H); 3.3-3.2 (m, IH); 3.15-3.05 (m, IH); 2.77-2.74 (m, IH); 2.68-2.62 (m, IH); 2.56-2.51 (m, 3H); 2.44-2.34 (m, 3H); 2.18-2.1 1 (m. I H); 1.81 -1.59 (m, 6H);

1.47-1.40 (m, 3H); 1.18-1.09 (m, IH).

Ex. 2.28: 2-[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-N-(3-met hyl-piperidin-l - yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.87-7.85 (m, IH); 7.01-6.92 (m, 2H); 6.03 (s, IH); 3.61-3.57 (m, IH); 3.14-2.93 (m, 3H); 2.78-2.74 (m, IH); 2.57-2.53 (m, IH); 2.46-2.33

(m, IH); 2.33-2.30 (m, IH); 2.20-2.14 (m, IH); 2.03-1.99 (m, IH); 1.84-1.60 (m, 6H);

1.42-1.25 (m, 4H); 0.9-0.87 (m, 3H).

Ex. 2.29: [l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-acetic acid 7V-(2-chloro- phenyl)-hydrazide IH NMR: (DMSO-J ₆ , 400 MHz) δ 9.80 (d, J = 2.4 Hz, IH); 7.85-7.79 (m, IH); 7.63-

7.57 (m, IH); 7.40 (d, J = 1.6 Hz, IH); 7.35-7.25 (m, 2H); 7.15-7.11 (m, IH); 6.75-6.71

(m, 2H); 3.58-3.56 (m, IH); 3.47-3.41 (m, IH); 2.61-2.56 (m, IH); 2.41-2.36 (m, IH);

2.13 (d, J = 7.2 Hz, 2H); 1.98-1.93 (m, IH); 1.72-1.67 (m, 2H); 1.49-1.44 (m, IH);

1.12-1.07 (m, IH). Ex. 2.30: [l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl] -acetic acid iV-(4-chloro- phenyl)-hydrazide

IH NMR (DMSO-d ₆ , 400MHz) δ 9.69 (d, J = 2.4 Hz, IH); 7.90 (d, J = 2.4 Hz, IH);

7.85-7.79 (m, IH); 7.63-7.57 (m, IH); 7.35-7.30 (m, IH); 7.14 (d, J= 8.8 Hz, 2H); 6.67

(d, J = 8.8 Hz, 2H); 3.56-3.54 (m, IH); 3.47-3.44 (m, IH); 2.60-2.55 (m, IH); 2.39- 2.34 (m, IH); 2.10 (d, J= 6.8 Hz, 2H); 1.97-1.95 (m, IH); 1.72-1.68 (m, 2H); 1.47-1.45

(m, IH); 1.07-1.04 (m, IH).

Ex. 2.31 : 2-[l-(2,4-Difluoro-benzenesulfonyl)-piperidin-3-yl]-iV-(4-me thyl-piperidin-l- yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.87-7.82 (m, IH); 7.01-6.92 (m, 2H); 6.03 (s, IH); 3.62-3.57 (m, IH); 3.20-3.10 (m, 2H); 3.03-2.96 (m, IH); 2.78-2.74 (m, IH); 2.57-2.53

(m, IH); 2.47-2.39 (m, 2H); 2.38-2.28 (m, 2H); 2.18-2.13 (m, IH); 1.84-1.60 (m, 4H);

1.58-1.38 (m, 4H); 1.17-1.09 (m, IH); 0.90 (d, J= 6.4 Hz, 3H).

Ex. 2.32: N-azepan-l-yl-2-[l-(3,4-dichloro-benzenesulfonyl)-piperidin- 3-yl] acetamide

IH NMR (CDCl ₃ , 300 MHz) δ 7.84-7.81 (m, IH); 7.61-7.56 (m, 2H); 6.48(s, IH); 3.5-

3.1(m, 2H); 3.55-3.45 (m, 2H); 3.05-2.97 (m, 3H); 2.80-2.75(m, I H); 2.62-2.59 (m,

IH); 2.50-2.35 (m, 2H); 2.25-2.00 (m, 2H); 1.80-1.55 (m, 8H); 1.39-1.2 (m, I H); 1.19-

0.98 (m, IH). Ex. 2.33: 2[l-(2,3-dichloro- benzenesulfonyl)-piperidin-3-yl]- /V-(hexahydro cyclopenta[c] pyrrole-2-yl)-acetamide

IH NMR (CDCl ₃ , 400 MHz) δ 7.85-7.81 (m, IH); 7.62-7.56 (m, 2H); 5.88(bs, IH);

3.56-3.53 (m, IH); 3.3-3.15 (m, IH); 3.12-2.98(m, IH); 2.95-2.88 (m, 2H); 2.68-2.64

(m, IH); 2.59-2.54 (m, 3H); 2.48-2.33 (m, 3H); 2.27-2.18 (m, 2H); 2.1-1.92 (m, IH); 1.81-1.67 (m, 3H); 1.60-1.41 (m, 3H); 1.39-1.2 (m, IH); 1.19-1.0 (m, IH).

Ex. 2.34: 2[l-(2,3-dichloro benzenesulfonyl)-piperidin-3-yl]- N-(3-methyl piperidinl- yl)acetamide

IH NMR (CDCl ₃ , 400 MHz) δ 7.85-7.81 (m, IH); 7.62-7.54 (m, 2H); 6.06 (s, IH);

3.54-3.45 (m, IH); 3.12-3.03 (m, 2H); 2.98-2.88 (m, 2H); 2.58-2.33 (m, 3H); 2.27-2.24 (m, IH); 2.20-2.16 (m, IH); 2.03-2.01 (m, IH); 1.88-1.74 (m, 5H); 1.73-1.61 (m, IH);

1.4-1.2 (m, IH); 1.2-1.0 (m, IH); 1-0.8 (m, 4H).

Ex. 2.35: 2[l-(2,3-dichloro benzenesulfonyl)-piperidin-3-yl]- iV-(4-methyl piperidinl- yl)acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.85-7.80 (m, IH); 7.62-7.54 (m, 2H); 6.03 (s, IH); 3.55-3.46 (m, IH); 3.16-2.98 (m, 3H); 2.95-2.54 (m, IH); 2.47-2.34 (m, 3H); 2.28-2.25

(m, IH); 2.21-2.15 (m, IH); 2.03-2.01 (m, IH); 1.80-1.74 (m, IH); 1.67-1.61 (m, 3H);

1.51-1.63 (m, 3H); 1.25-1.19 (m IH); 1.1-0.75 (m, 4H).

Ex 2.36: [l-(3,4-dichloro-benzenesulfonyl)-piperidin-3-yl]aceticacid JV-(4- chlorophenyl- phenyl) hydrazide IH NMR (DMSO-^ _J , 400 MHz) δ 9.68 (s, IH); 7.94-7.90 (m, 3H); 7.67 (d, J = 8.4 Hz,

IH); 7.15 (d, J = 8 Hz, 2H); 6.67 (d, J = 8 Hz, 2H); 3.51-3.42 (m, 2H); 2.26-2.21 (m,

IH); 2.11-2.09 (m, 2H); 1.95 (s, IH); 1.70-1.60 (m, 2H); 1.47-1.44 (m, IH); 1.22 (s,

IH); 1.03-1.00(m, IH).

Ex. 2.37: [l-(3,4-dichlorυ-benzenesulfonyl)-piperidin-3-yl]aceticacid iV-(2- chlorophenyl phenyl) hydrazide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.83 (s, IH); 7.60-7.55 (m, 2H); 7.43 (s, IH); 7.34-7.16

(m, 2H); 6.93-6.80 (m, 2H); 6.42 (s, IH); 3.49-3.48 (m, IH); 3.20-3.17 (m, IH); 3.11-

3.04 (m, IH); 2.85-2.82 (m, IH); 2.51-2.46 (m, IH); 2.31-2.18 (m, 2H); 1.78-1.73 (m, 2H); 1.72-1.65 (m, IH); 1.35-1.27 (m, IH).

Ex. 2.38: l-{2[l-(2,3-dichloro benzenesulfonyl)-piperidin-3-yI]-acetylamino} - piperidin-3-carboxylic acid, methyl ester IH NMR (CDCl ₃ , 300 MHz) δ 7.84-7.81 (m, IH); 7.62-7.56 (m, 2H); 6.6-6.2 (m, I H); 3.70 (s, 3H); 3.54-3.36 (m, 2H); 3.35-3.02 (m, 2H); 2.84-2.78 (m, I H); 2.72-2.55 (m, 2H); 2.48-2.29 (m, 3H); 2.27-2.08 (m, 2H); 2.03-2.01 (m, I H); 1.97-1.66 (m, 3H); 1.39-1.19 (m, 3H); 1.18-0.9(m, IH).

Ex. 2.39: N-Azepan-l-yl-2-[l-(2-chloro-benzenesulfonyl)-piperidin-3-yl ]-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 8.06-8.00 (m, IH); 7.52-7.45 (m, 2H); 7.40-7.35 (m, IH); 6.43 (s, IH); 3.67-3.61 (m, IH); 3.29-3.27 (m, IH); 3.05-2.92 (m, 3H); 2.77- 2.67(m, 2H); 2.42-2.40 (m, IH); 2.29-2.13 (m, IH); 1.92-1.74 (m, IH); 1.72-1.54 (m, 12H); 1.23-1.08 (m, IH).

The following examples were prepared according to the general scheme 3 above. Example 3.1

2-[l-(4-Chloro-2-fluoro-benzenesulfonyl)-piperidin-3-yl]-iV- piperidin-l-yl-acetamide Step A : [l-(4-Chloro-2-fluoro-benzenesulfonyl) -piperidin-3-yl] -methanol 3-piperidine methanol (2.39 g, 20.78 mmol, 1 equiv.) was dissolved in dry dichloromethane (25 mL) in a round bottomed flask equipped with N ₂ balloon. Triethyl amine (2.1 g, 3 mL, 20.78 mmol, 1 equiv.) was added to the solution and stirred for 20 minutes at room temperature. After stirring for 20 minutes, 4-Chloro-2-fluorobenzene sulfonyl chloride (5g, 21.82 mmol, 1.05 equiv.) was added to the reaction mixture at 0 ⁰ C to 5 ⁰ C. Then the reaction mixture was stirred at room temperature and monitored by TLC till completion. The reaction mixture was diluted with dichloromethane and cold water and further stirred. The layers were separated and the organic layer was washed with the water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to get crude product. The crude product was recrystalised from mixture ethyl acetate and hexane to get pure product (5.7 g, 18.47 mmol, 92 %) IH NMR: (CDCl ₃ , 400 MHz) δ 7.81-7.77 (m, IH); 7.28-7.26 (m, IH); 7.23-7.22 (m, IH); 3.71-3.61 (m, IH); 3.60-3.51 (m, 3H); 2.78-2.73 (m, IH); 2.61-2.56 (m, IH); 1.89-1.83 (m, IH); 1.80-1.73 (m, 2H); 1.67-1.60 (m, IH); 1.5-1.4 (m, IH); 1.15 (m, IH). Step B: 1 - (4-Chloro-2-flιιoro-ben∑enesιιlfonyl) -3-iodomethyl-piperidine

Triethyl amine (2.26g, 3.1 mL, 22.36 mmol, 1.15 equiv.) was added to the solution of the alcohol obtained above (5.7g, 18.47 mmol, 1 equiv.) in dry dichloromethane (30 mL) in a round bottomed flask equipped with CaCl ₂ guard tube at room temperature. Methane sulfonyl chloride (2.45 g, 1.66 mL, 20.32 mmol, 1.1 equiv.) was added to the above reaction mixture at 0-5 ⁰ C. The reaction mixture was stirred at room temperature and monitored by TLC for completion. The mixture was diluted with dichloromethane, washed with water, brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to yield the mesylate derivative, which was used without further purification. IH NMR: (CDCl ₃ , 400 MHz) δ 7.81-7.77 (m, IH); 7.29-7.24 (m, 2H); 4.19-4.15 (m, IH); 4.13-4.09 (m, IH); 3.67-3.62 (m, IH); 3.54-3.51 (m, IH); 3.04 (s, 3H); 2.87-2.82 (m, IH); 2.76-2.71 (m, IH); 2.15-2.11 (m, IH); 1.79-1.76 (m, 2H); 1.68-1.62 (m, IH); 0.88-0.83 (m, IH). The mesylate derivative (7.3 g, 18.93 mmol, 1 equiv.) was dissolved in dry dimethyl formamide (35 mL) in a round bottomed flasks equipped with air condenser and N ₂ balloon. Potassium iodide (18.8 g, 133.61 mmol, 6 equiv.) was added to the mixture. Then the reaction mixture was heated upto 80 ⁰ C to 85 ⁰ C. The reaction was monitored by TLC for completion. Then the reaction mixture was cooled to 0 ⁰ C and slowly crushed ice was added to the reaction mixture to get the yellow solid. It was further diluted with cold water with stirring. The solid thus obtained was filtered, washed with water, air-dried to furnish corresponding iodo derivative (7.7 g, 18.9 mmol, 81%) IH NMR: (CDCl ₃ , 400 MHz) δ 7.82-7.78 (m, IH); 7.29-7.29 (m, IH); 7.27-7.23 (m, IH); 3.80-3.77 (m, IH); 3.64-3.61 (m, IH); 3.12-3.05 (m, 2H); 2.70-2.64 (m, IH); 2.50-2.45 (m, IH); 1.91-1.87 (m, IH); 1.80-1.73 (m, 2H); 1.69-1.63 (m, IH); 1.32-1.14 (m, IH).

Step C: [l-(4-Chloro-2-fluoro-benzenesulfonyl)-pipeήdin-3-yl]-aceto nitrile The iodo compound (6.9 g, 16.52 mmol, 1 equiv.) was dissolved in dry dimethyl formamide (35 ml ,) in a round bottomed flask (250 mL) equipped with N ₂ balloon. 18- Crown-6 ether (0.14g, 0.02 w/w) was added to the reaction mixture followed by portion wise addition of NaCN (0.89 g, 1.1 equiv.). The reaction was stirred at room temperature for 16-18h. Then, the reaction mixture was diluted with cold water and extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over sodium sulphate and concentrated in vacuo to furnish crude cyano

derivative. The crude material was purified by column chromatography to obtain pure white solid (5.3 g, 17.19 mmol, 99%).

IH NMR: (CDCl ₃ , 400 MHz) δ 7.79-7.77 (m, I H); 7.30-7.26 (m, IH); 7.25-7.24 (m, IH); 3.70-3.67 (m, IH); 3.63-3.58 (m, IH); 2.96-2.88 (m, IH); 2.79-2.73 (m, I H); 2.45-2.33 (m, 2H); 2.18-2.05 (m, IH); 1.95-1.87 (m, IH); 1.82-1.78 (m, I H); 1.71-1.63 (m, IH); 1.39-1.29 (m, IH).

Step D: [l-(4-Chloro-2-fluoro-benzenesulfonyl)-piperidin-3-yl] -acetic acid, methyl ester Anhydrous hydrochloride gas was passed through two necked round bottomed flask equipped with condenser and CaCl ₂ guard tube containing the nitrile derivative from above(5.3g, 17.19 mmol, 1 equiv.) in dry methanol (75 mL) for 1.5h. The solvent was removed in vacuo to get solid residue. Water was added to this residue and extracted with ethyl acetate. The combined organic layers washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain the desired white solid (5.6 g, 16.39 mmol, 93%).

IH NMR: (CDCl ₃ , 400 MHz) δ 7.80-7.76 (m, IH); 7.28-7.26 (m, IH); 7.23-7.22 (m, IH); 3.67-3.65 (m, 3H); 3.65-3.58 (m, 2H); 2.76-2.71 (m, IH); 2.51-2.48 (m, IH); 2.34-2.28 (m, IH); 2.24-2.19 (m, IH); 2.15-2.12, (m, IH); 1.82-1.72 (m, 2H); 1.77- 1.72(m, IH); 1.13 (m, IH). Step E: [l-(4-Chloro-2-fluoro-benzenesulfonyl)-piperidin-3-yl] -acetic acid

Lithium hydroxide (1.37g, 32.28 mmol, 2 equiv.) in water (60 mL) was added to the stirring solution of ester (5.5g, 16.39 mmol, 1 equiv.) in tetrahydrofuran (60 mL) at room temperature. The reaction was stirred for 16h. The solvent was removed in vacuo to obtain residue, diluted with water and washed with ethyl acetate to remove organic impurities. The aqueous layer was separated and cooled to 0 ⁰ C, acidified with HCl (0.1 N). The separated solid was filtered off, dried in air to constant weight (4.7g, 14 mmol,

IH NMR: (CDCl ₃ , 400MHz) δ 7.81-7.77 (m, IH); 7.28-7.26 (m, IH); 7.23-7.23 (m, IH); 3.68-3.65 (m, IH); 3.61-3.58 (m, IH); 2.78-2.73 (m, IH); 2.57-2.53 (m, IH); 2.39-2.33 (m, IH); 2.30-2.24 (m, IH); 2.18-2.12 (m, IH); 2.04 (m, IH); 1.87-1.76 (m, 2H); 1.76-1.72 (m, 2H); 1.15 (m, IH).

Step F: 2-[l-(4-Chloro-2-fluoro-benzenesulfonyl)-piperidin-3-yl]-N-p iperidin-l-yl- acetamide

To mixture of the acid (0.5g, 1.49 mmol, 1 equiv.) and DMAP (0.18 g, 1.49 mmol, 1 equiv.), dry dichloromethane (10 niL) in a round bottomed flask was added EDCl (0.57g, 2.98 mmol, 2 equiv.) under nitrogen atmosphere, followed by 1- aminopiperidine (0.17g, 0.17 mL, 1.63 mmol, 1.1 equiv.) at 0 ⁰ C to 5 ⁰ C. The reaction mixture was brought to room temperature and stirred for 16h. Then the reaction mixture was diluted with dichloromethane (10 mL). The organic layer washed with water, brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The compound was purified by column chromatography using (0.7:99.3) methanol xhloro form as eluent to furnish the desired product (0.32g, 51%). IH NMR: (CDCl ₃ , 400 MHz) δ 7.80-7.73 (m, IH); 7.27-7.22 (m, 2H); 6.06 (s, IH); 3.63-3.57(m, IH); 3.15 (m, IH); 2.95-3.1 (m, IH); 2.75-2.65 (m, 2H); 2.55-2.45 (m, IH); 2.43-2.38 (m, IH); 2.38-2.31 (m, 2H); 2.27-2.10 (m, IH); 1.95-1.79 (m, IH); 1.75-1.69 (m, 7H); 1.42-1.41 (m, 2H); 1.15-1.12 (m, IH).

The following compounds were prepared in a similar way as described in example 3.1

Ex. 3.2: 2- [ 1 -(4-Chloro-2-fluoro-benzenesulfonyl)-piperidin-3-yl] -7V-morpholin-4-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.80-7.73 (m, IH); 7.28-7.22 (m, 2H); 6.15 (s, IH);

3.84-3.81 (m, 3H); 3.56-3.52 (m, IH); 3.16-3.11 (m, IH); 2.87-2.82 (m, 3H); 2.68-2.62 (m, IH); 2.57-2.52 (m, IH); 2.39- 2.33 (m IH); 2.30-2.23 (m, IH); 2.07-2.02 (m, IH);

1.79-1.95 (m, IH); 1.76-1.71 (m, IH); 1.64-1.61 (m, 2H); 1.50-1.40 (m, IH); 1.15 (m,

IH).

Ex. 3.3: 2-[l -(2-Chloro-4-fluoro-benzenesulfonyl)-piperidin-3-yl]-iV-pipe ridin- 1 -yl- acetamide I H NMR: (CDCl ₃ , 400 MHz) δ 8.09-8.02 (m, III); 7.29-7.23 (m, IH); 7.10-7.06 (m,

IH), 6.06 (s, IH); 3.63-3.62 (m, 2H); 3.45-3.32 (m, IH); 3.14-2.89 (m, 2H); 2.75-2.66

(m, 2H); 2.40-2.38 (m, IH); 2.28-2.25 (m, 2H); 2.23-1.98 (m, 2H); 1.86-1.81 (m, IH);

1.76-1.51 (m, 6H); 1.42-1.41 (m, IH); 1.15-1.09 (m, IH).

Ex. 3.4: 2-[l -(2-Chloro-4-fluoro-benzenesulfonyl)-piperidin-3-yl]-iV-morp holin-4-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.08-8.01 (m, IH); 7.26-7.20 (m, IH); 7.11-7.06 (m,

IH); 6.13 (s, IH); 3.83-3.81 (m, 3H); 3.77-3.68 (m, IH); 3.28-3.19 (m, 2H); 3.09-3.02

(m, IH); 2.86- 2.81 (m, 3H); 2.79-2.75 (m, IH); 2.48-2.46 (m, IH); 2.41-2.39 (m, IH);

2.35-2.30 (m, IH); 2.05-2.04 (m, IH); 1.95-1.80 (m, IH); 1.76-1.72 (m, IH); 1.33 (m,

IH); 1.15 (m, IH).

Ex. 3.5: 2-[l-(4-Amino-benzenesulfonyl)-piperidin-3-yl]-N-piperidin-l -yl-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.54-7.48 (m, 2H); 6.72 (dd, J= 1.2, 6.8 Hz, 2H); 4.1 1 - 4.09 (m, 2H); 3.50-3.41 (m, IH); 2.9-2.89 (m, IH); 2.80-2.76 (m, 2H); 2.44-2.40 (m,

IH); 2.38-2.35 (m, IH); 2.33-2.30 (m, IH); 2.28-2.25 (m, 2H); 2.17-2.02 (m, IH);

1.74-1.69 (m, 3H); 1.67-1.59 (m, 3H); 1.42-1.41 (m, 2H); 1.28-1.25 (m, IH).

Ex. 3.6: 2-[l-(4-Acetylamino-benzenesulfonyl)-piperidin-3-yl]-N-piper idin-l -yl- acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.76-7.66 (m, 4H); 7.52 (s, IH); 6.12 (s, IH); 3.49 (s,

3H); 3.52-3.47 (m, IH); 2.99-2.96 (m, 2H); 2.88-2.85 (m, 2H); 2.50-2.36 (m, 2H);

2.33-2.28 (m, 2H); 2.25-2.20 (m, 4H); 1.74-1.70 (m, 5H); 1.36-1.33 (m, 2H); 1.27-1.22

(m, IH).

Ex 3.7: 2-[l-(3-Chloro-4-methoxy-benzenesulfonyl)-piperidin-3-yl]-iV -piperidin-l-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.75 (dd, J = 2.4, 15.2 Hz, IH); 7.66-7.60 (m, IH);

7.01 (d, J = 8.8 Hz, IH); 6.36(s, IH); 3.97(s, 3H); 3.52-3.46 (m, IH); 3.01-2.95 (m,

2H); 2.94-2.68 (m, 2H); 2.47-2.27 (m, 4H); 2.22-2.17 (m, IH); 1.79-1.57 (m, 8H);

1.56-1.28 (m, 2H); 1.18-0.98 (m, IH). Ex 3.8: 2-[l-(3-Chloro-4-methoxy-benzenesulfonyl)-piperidin-3-yl]-iV -morpholin-4-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.73 (dd, J= 2, 14 Hz, IH); 7.65-7.59 (m, IH); 7.01 (d,

J= 8.8 Hz, IH); 6.50 (s, IH); 3.97 (s, 3H); 3.84-3.79 (m, 3H); 3.41-3.32 _. (m, IH); 2.94-

2.87 (m, 4H); 2.71-2.60 (m, 2H); 2.51-2.45 (m, IH); 2.39-2.25 (m, 2H); 1.77-1.67 (m, 2H); 1.66-1.61 (m, 2H); 1.28-1.42 (m, IH); 1.01-1.2(m, IH).

Ex. 3.9: 2- [ 1 -(3 -Chloro-4-fluoro-benzenesulfonyl)-piperidin-3 -yl] -N-piperidin- 1 -yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.85-7.79 (m, IH); 7.68-7.63 (m, IH); 7.31-7.29 (m,

IH); 6.07 (s, IH); 3.54-3.46 (m, 2H); 3.06-2.75 (m, 2H); 3.1-2.7 (m, IH); 2.42-2.03 (m, 5H); 1.80-1.65 (m, 8H); 1.48-1.25 (m, IH); 1.15-1.1 (m, IH); 1.05-0.82 (m, IH).

Ex. 3.10: 2-[l-(3-Chloro-4-fluoro-benzenesulfonyl)-piperidin-3-yl]-N-m orpholin-4-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.84-7.79 (m, IH); 7.78-7.6 (m, IH); 7.32-7.27 (m, IH); 6.13 (s, IH); 4.08-3.83 (m, 2H); 3.80-3.64 (m I H); 3.47-3.37 (m, I H); 3.22-2.81 (m, 4H); 2.80-2.72 (m, IH); 2.61-2.50 (m, 2H); 2.48-2.22 (m, 2H); 1.89-1.78 (m, 2H); 1.74-1.61 (m, 2H); 1.41-1.36 (m, IH); 1.09-0.91 (m, IH). Ex. 3.11 : 2-[l-(5-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-p iperidin-l -yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.64-7.54 (m, IH); 7.32-7.25 (m, IH); 7.17-7.12 (m, IH); 6.08 (s, IH); 3.60-3.52 (m, IH); 3.27-2.99 (m, 2H); 2.95-2.82 (m, 2H); 2.81-2.62 (m, 2H); 2.59-2.56 (m, IH); 2.27 (s, 3H); 2.40-2.38 (m, IH); 2.26-2.22 (m, 3H); 2.15- 2.11 (m, IH); 1.71-1.5 (m, 6H); 1.48-1.15 (m, IH); 1.14-0.96 (m, IH).

Ex. 3.12: 2-[l-(5-Fluoro-2-methyl-benzenesulfonyl)-piperidin-3-yl]-N-m oφholin-4-yl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.62-7.52 (m, IH); 7.32-7.27 (m, IH); 7.17-7.13 (m, IH); 6.12 (s, IH); 3.83-3.80 (m, 2H); 3.56-3.24 (m, IH); 3.05-2.80 (m, 3H); 3.21-2.88 (m, 2H); 2.87-2.82 (m, IH); 2.69-2.64 (m, IH); 2.57 (s, 3H); 2.46-2.02 (m, 3H); 1.77- 1.61 (m, 4H); 1.5-1.32 (m, IH); 1.3-1.009 (m, IH).

Ex. 3.13: 2-[l-(2,5-Dichloro-thiophene-3-sulfonyl)-piperidin-3-yl]-N-p iperidin-l-yl- acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 7.04-7.00 (m, IH); 6.07 (s, IH); 3.64-3.57 (m, IH); 3.31-3.12 (m, IH); 3.02-3.01 (m, IH); 2.79-2.75 (m, 2H); 2.62-2.57 (m, IH); 2.45-2.40

(m, IH); 2.28-2.24 (m, 2H); 1.95-1.79 (m, IH); 1.78-1.51 (m, 7H); 1.44-1.40 (m, 2H);

1.34-1.18 (m, IH); 1.15-1.01 (m, IH).

Ex. 3.14: 2-[l-(2,5-Dichloro-thiophene-3-sulfonyl)-piperidin-3-yl]-N-m oφholin-4-yl- acetamide IH νMR: (CDCl ₃ , 400 MHz) δ 7.03-7.00 (m, IH); 6.1 2(s, IH); 4.10-3.91 (m, 3H);

3.95-3.69 (m, IH); 3.67-3.58 (m, IH); 3.28-3.05 (m, IH); 3.01-2.85 (m, 3H); 2.80-2.75

(m, IH); 2.65-2.45 (m, IH); 2.40-2.25 (m, IH); 2.21-2.00 (m, IH); 1.81-1.61 (m, 2H);

1.35-1.12 (m, 3H); 0.97-0.78 (m, IH).

Ex. 3.15 : 2-[ 1 -(2-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-piperidin- 1 -yl-acetamide IH νMR: (CDCl ₃ , 400 MHz) δ 7.84-7.81 (m, I H); 7.57-7.54 (m, IH); 1.29-1 Al (m,

2H); 6.08 (s, IH); 3.71-3.53 (m, IH); 3.42-3.25 (m, IH); 3.20-3.08 (m, IH); 3.06-2.92

(m, IH); 2.81-2.74 (m, 2H); 2.55-2.25 (m, 3H); 2.33-2.12 (m, 2H); 1.75-1.71 (m, IH);

1.69-1.58 (m, 5H); 1.42-1.31 (m, 3H); 1.16-1.09 (m, IH).

Ex. 3.16: 2-[l-(2-Fluoro-benzenesulfonyl)-piperidin-3-yl]-λ^-moφholi n-4-yl-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.84-7.80 (m, IH); 7.58-7.55 (m, IH); 7.29-7.17 (m, 2H); 6.14 (s, IH); 3.86-3.81 (m, 2H); 3.73-3.64 (m IH); 3.57-3.53 (m, I H); 3.49-3.31 (m, IH); 3.13-3.06 (m, 2H); 2.95-2.81 (m, 2H); 2.68-2.53 (m, 2H); 2.40-2.33 (m, I H); 2.28-2.10 (m, IH); 2.07-2.02 (m, IH); 1.75-1.59 (m, 4H); 1.27-1.09(m, I H).

Ex. 3.17: 2-[l-(2-Fluoro-benzenesulfonyl)-piperidin-3-yl]-N-(hexahydro -cyclopenta[c] pyrrol -2-yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.87-7.81 (m, IH); 7.58-7.55 (m, IH); 7.30-7.18 (m, 2H); 5.93 (s, IH); 3.65-3.60 (m, IH); 3.27-3.23 (m, IH); 3.13-2.96 (m, IH); 2.88-2.74 (m, IH); 2.71-2.66 (m, IH); 2.55-2.53 (m, 2H); 2.50-2.43 (m, IH); 2.41-2.30 (m, 2H); 2.17-2.16 (m, IH); 1.85-1.79 (m, 3H); 1.69-1.64 (m, 2H); 1.63-1.58 (m, 3H); 1.40- 1.3 l(m, 3H); 1.15-1.05 (m, IH).

Ex 3.18: 2-[l -(2-FIuoro-5-methyl-benzenesulfonyl)-piperidin-3-yl]-iV-pipe ridin- 1 -yl- acetamide IH NMR: (DMSO-^ ₆ , 400 MHz) δ 8.72 (bs, IH); 7.54-7.51 (m, 2H); 7.37-7.32 (m, IH); 3.54-3.48 (m, 2H); 2.63-2.60 (m, 2H); 2.35-2.33 (m, IH); 2.35 (s, 3H); 2.29-2.18 (m, 2H); 1.90-1.84 (m, 2H); 1.68-1.59 (m, 3H); 1.52-1.38(m, 6H); 1.23-1.21 (m, 2H); 1.06-1.04 (m, IH). Ex. 3.19: 2-[l-(2-Fluoro-5-methyl-benzenesulfonyl)-piperidin-3-yl]-N-m oφholin-4-yl- acetamide

IH NMR: (DMS0-d ₆ , 400 MHz) δ 8.89 (bs, IH); 7.54-7.52 (m, 2H); 7.37-7.32 (m, IH); 3.73-3.57 (m, 3H); 3.46 (m, 2H); 2.71-2.67 (m, 4H), 2.55-2.48 (m, IH), 2.34 (s, 3H,) 2.31-2.24 (m, 2H), 1.91-1.85 (m, 2H), 1.67-1.60 (m, 2H), 1.44-1.41 (m, IH), 1.22 (m, IH) 1.03-0.98 (m, IH). Ex. 3.20: 2-[l-(3-Fluoro-4-methyl-benzenesulfonyl)-piperidin-3-yl]-N-( 3-methyl- piperidin- 1 -yl)-acetamide

IH NMR: (DMS0-<&, 400 MHz) δ 8.72 (bs, IH); 7.57-7.55 (m, IH); 7.45-7.43 (m, 2H); 3.45-3.43 (m, 2H); 2.80-2.78 (m, 2H); 2.39-2.28 (m, 2H); 2.32 (s, 3H); 2.23-2.22 (m, IH); 2.1-2.04 (m, 2H); 1.89-1.86 (m, 2H); 1.62-1.57(m, 5H); 1.48-1.44 (m, 2H); 1.25-1.19 (m, IH); 0.83-0.81 (m, 4H).

Ex. 3.21: 2-[l-(3-Fluoro-4-methyl-benzcncsullbiiyl)-pipcridin-3-yl] N piperidin- 1 -yl- acetamide

IH NMR (CDCl ₃ , 400 MHz) δ 8.72 (bs, IH); 7.59-7.55 (m, IH); 7.45-7.42 (m, 2H);

3.50-3.3.40 (m, 2H); 2.72-2.66 (m, IH); 2.63-2.52 (m, 3H); 2.32 (s, 3H); 2.31 -2.28 (m, IH); 2.24-2.22 (m, IH); 2.07-2.02 (m, IH); 1.86 (bs, 2H); 1.66-1.43 (m, 7H); 1.32-1.31

(m, IH); 1.23-1.21 (m, IH); 0.95-0.92 (m, IH). Ex. 3.22: 2-[l-(3-Fluoro-4-methyl-benzenesulfonyl)-piperidin-3-yl]-N-m orpholin-4-yl- acetamide

IH NMR (CDCl ₃ , 400 MHz) δ 8.89 (bs, IH); 7.59-7.55 (m, IH); 7.45-7.43 (m, 2H);

3.60-3.58 (m, 3H); 3.48-3.39(m, 3H); 2.71-2.68 (m, 3H); 2.66-2.64(m, IH); 2.32 (s,

3H); 2.31-2.25 (m, 2H); 2.08-2.06 (m, IH); 1.88 (bs, 2H); 1.66-1.59 (m, 2H); 1.45-1.43 (m, IH); 0.94-0.92 (m, IH).

Ex. 3.23: [l-(4-Nitro-benzenesulfonyl)-piperidin-3-yl]-acetic acid 7V-(2,4-dichlόrό- phenyl)-hydrazide

IH NMR: (OMSO-d ₆ , 400 MHz) δ 9.82 (d, J = 1.2 Hz, IH); 8.44 (d, J = 9.2 Hz, 2H);

7.98 (d, J = 8.8 Hz, 2H); 7.63 (s, IH); 7.40 (d, J = 2.4 Hz, IH); 7.19 (dd, J = 2.4, 8.8 Hz, IH); 6.70 (d, J= 8.8 Hz, IH); 3.55-3.44 (m, 2H); 3.28-3.24 (m, IH); 2.49-2.23 (m,

IH); 2.14-2.1 l(m, 2H); 1.67 (s, IH); 1.70-1.62 (m, 2H); 1.49-1.43 (m, IH); 1.03-0.95

(m, IH).

Ex. 3.24 : iV-Morpholin-4-yl-2-[ 1 -(4-nitro-benzenesulfonyl)-piperidin-3 -yl] -acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.37 (d, J = 7.6 Hz, 2H); 7.95 (m, 2H); 6.17 (s, IH); 3.85-3.68 (m, 4H); 3.53-3.42 (m, IH); 3.17-3.14 (m, IH); 3.10-2.91 (m, 3H); 2.74-2.69

(m, IH); 2.62-2.49 (m, IH); 2.40-2.07 (m, 2H); 1.79-1.76 (m, IH); 1.70-1.63 (m, 4H);

1.34-1.25 (m, IH).

Ex 3.25 : 2-[ 1 -(4-Nitro-benzenesulfonyl)-piperidin-3-yl]-iV-piperidin- 1 -yl-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.39-8.36 (m, 2H); 7.97-7.92 (m, 2H); 6.10 (s, IH); 3.62-3.53 (m, 2H); 2.98-2.91(m, 3H); 2.42-2.37 (m, 2H); 2.26-2.24 (m, 2H); 1.80-1.74

(m, 3H); 1.67-1.56 (m, 8H); 1.09-1.06 (m, IH).

The following compounds were prepared according to the general scheme B described above.

Example 4.1 2-(l-Benzenesulfonyl-piperidin-3-yl)-iV-methyl-iV-piperidin- l-yl-acetamide

To the suspension of NaH (0.13 g, 2.73 mmol, 2 equiv., 60% dispersion in mineral oil) in dry tetrahydrofuran (3 mL) at O ⁰ C was added the compound obtained from example

1.1 (0.5 g, 1.36 mmol, 1 equiv.) and stirred for about 20 minutes. Methyl iodide (0.25

mL, 4.08 mmol, 3 equiv.) in dry tetrahydrofuran (2 mL) was added dropwise at 0 ⁰ C and stirred for about 5 minutes at the same temperature with continuous stirring and the reaction was monitored by TLC till completion. The solvent was removed in vacuo, diluted with ethyl acetate and washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated to give crude product. The product was purified by column chromatography using MeOH:CHCl ₃ (0.6:99.4) as mobile phase to obtain pure compound (0.17g, 0.44 mmol, 30%).

IH NMR (CDCl ₃ , 400 MHz) δ 7.76 (d, J = 8 Hz, 2H); 7.63-7.48 (m, 3H); 3.57-3.49 (m, 2H); 2.89 (s, 3H); 2.87-2.64 (m, 4H); 2.61-2.47 (m, 2H); 2.43-2.38 (m, I H); 2.29-2.24 (m, IH); 2.15-2.10 (m, IH); 1.77-1.64 (m, 5H); 1.63-1.57 (m, 3H); 1.21-0.89(m, 2H).

The following compounds were prepared in a similar way as described in example 4.1

Ex. 4.2: 2-(l-Benzenesulfonyl-piperidin-3-yl)-λ/-methyl-λ ^r -(3-methyl-piperidin-l-yl)- acetamide IH NMR (CDCl ₃ , 400 MHz) δ 7.76 (d, J= 8 Hz, 2H); 7.58-7.56 (m, IH); 7.54-7.50 (m, 2H); 3.54-3.47 (m, 2H); 2.88 (s, 3H); 2.70-2.68 (m, 2H); 2.56-2.50 (m, IH); 2.48-2.38 (m, 2H); 2.29-2.23 (rη, 2H); 2.09-2.04 (m, 2H); 1.74-1.64 (m, 5H); 1.62-1.59(m, 4H); 0.94 (d, J= 6.4 Hz, 3H). Ex. 4.3: 2-[l-(3 -Chloro-2-methyl-benzenesulfonyl)-piperidin-3 -yl] -N-methyl-iV- piperidin-1-yl-acetamide

IH NMR (CDCl ₃ , 400 MHz) δ 7.87 (dd, J = 1.2, 8 Hz, IH); 7.56 (dd, J = 1.2, 8 Hz, IH); 7.26-7.22 (m, IH); 3.57-3.53 (m, 2H); 2.86 (s, 3H); 2.79-2.78 (m, IH); 2.68-2.64 (m, IH); 2.62-2.56 (m, 4H); 2.46-2.41 (m, 2H); 2.1-1.9 (m, IH); 1.88-1.7 (m, 2H); 1.75-1.71 (m, 4H); 1.61-1.55 (m, 5H); 1.13-1.10 (m, 2H). Ex. 4.4: 2-(l-Benzencsulfonyl-piperidin-3-yl)-N-ethyl-N-piperidin-l-y l-acctainide

IH νMR: (CDCl ₃ , 400 MHz) δ 7.76 (dd, J= 1.2, 8 Hz, 2H); 7.60-7.56 (m, IH); 7.54- 7.50 (m, 2H); 3.55-3.50 (m, 2H); 3.42 (q, J= 12 Hz, 2H); 2.80-2.75 (m, 2H); 2.67-2.62 (m, 2H); 2.49-2.36 (m, 3H); 2.29-2.24 (m, IH); 2.14-2.12 (m, IH); 1.78-1.71 (m, 5H); 1.68-1.55 (m, 3H); 1.31-1.19 (m, 3H); l.l-0.9(m, 2H). Ex. 4.5: N-Methyl-2-[l-(4-nitro-benzenesulfonyl)-piperidin-3-yl]-N-pi peridin-l-yl- acetamide

IH νMR: (CDCl ₃ , 400 MHz) δ 8.37 (d, J= 8.4 Hz, 2H); 7.96 (d, J= 8.4 Hz, 2H); 3.65- 3.58 (m, 2H); 3.55 (s, 3H); 2.89-2.62 (m, 3H); 258-2.55 (m, IH); 2.53-2.5 l(m, IH);

2.49-2.44 (m, 2H); 2.42-2.40(m, IH); 2.37-2.32 (m, IH); 2.15-2.09 (m, IH); 1.79-1.72 (m, 6H); 1.69-1.58 (m, 2H); 1.15-0.95 (m, IH).

Ex. 4.6: N-Azepan-l-yl-2-[l-(2-chloro-benzenesulfonyl)-piperidin-3-yl ]-N-methyI- acetamide IH NMR (CDCl ₃ , 400 MHz): 8.05 (dd, J = 1.6, 8 Hz, IH); 7.51-7.44 (m, 2H); 7.39- 7.35 (m, IH); 3.65-3.62 (m, 2H); 2.94-2.87 (m, 3H); 2.89 (s, 3H); 2.88-2.80 (m, 2H); 2.72-2.67(m, IH); 252-2.51 (m, 2H); 2.2-2.1 (m, IH); 1.9-1.8 (m, IH); 1.85-1.45 (m, 10H); 1.15-0.9 (m, IH).

Ex. 4.7: 2-( 1 -Benzenesulfonyl-piperidin-3-yl)-N-(hexahydro-cyclopenta[c]p yrrol-2-yl)- iV-methyl-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.76 (d, 2H, J= 7.2 Hz); 7.58-7.50 (m, 3H); 3.54-3.46 (m, 2H); 2.91-2.88 (m, IH); 2.84 (s, 3H); 2.56-2.48 (m, 4H); 2.43-2.42 (m, IH); 2.32- 2.29 (m, 2H); 2.14-2.09 (m, IH); 1.92-1.90 (m, 2H); 1.76-1.74 (m, 9H); 1.06-0.97 (m, IH). Ex 4.8: N-Azepan-l-yl-2-[l-(4-fluoro-benzenesulfonyl)-piperidin-3-yl ]-N-methyl- acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.80-7.76 (m, 2H); 7.22-7.18 (m, 2H); 3.53-3.51 (m, 2H); 2.95 (s, 3H); 2.95-2.80 (m, 4H); 2.58-2.47 (m, 3H); 2.34-2.29 (m, 2H); 2.17-2.16 (m, IH); 1.74-1.59 (m, 9H); 1.05-1.03 (m, 2H). Ex 4.9: 2-[l-(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-7V-(hexahydr o-cyclopenta[c] pyrrol-2-yl)- N-methyl-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.05-8.01 (m, IH); 7.51-7.44 (m, 2H); 7.39-7.35 (m, IH); 3.67-3.61 (m, 2H); 2.95 (s, 3H); 2.88-2.81 (m, 2H); 2.69-2.63 (m, 5H); 2.54-2.50 (m, IH); 2.46-2.44 (m, IH); 1.92 (m, 2H); 1.85-1.84 (m, IH); 1.83-1.80 (m, IH); 1.76- 1.73 (m, 2H); 1.62-1.56 (m, 3H); 1.30-1.23 (m, IH); 1.09-1.05 (m, IH).

Ex 4.10: 2-[ 1 -(2-Chloro-benzenesulfonyl)-piperidin-3-yl]-N-methyl-N-(3 -methyl-piper idin- 1 -yl)-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 8.03 (dd, J= 7.6, 1.2 Hz, IH); 7.51-7.44 (m, 2H); 7.39- 7.37 (m, IH); 3.63 (d, J = 12 Hz, 2H); 2.86 (s, 3H); 2.68-2.64 (m, 3H); 2.54-2.45 (m, IH); 2.44-2.41 (m, 2H); 2.26-2.21 (m, IH); 2.14 (m, IH); 1.75-1.73 (m, 2H); 1.73-1.70 (m, 4H); 1.25 (s, IH); 1.15 (m, 2H); 0.89 (d, J= 6.4 Hz, 3H); 0.88 (m, IH). Ex. 4.11: 2-[l-(2,3-Dichloro-benzenesulfonyl)-piperidin-3-yl]-N-methyl -N-morpholin- 4-yl-acetamide

IH NMR: (CDCl ₃ , 400 MHz) δ 7.99 (dd, J = 1.6, 8 Hz, IH); 7.65 (dd, J = 1.6, 8 Hz, IH); 7.33 (t, IH, J = 7.6); 3.93-3.89 (m, 2H); 3.71-3.56 (m, 4H); 3.01 -2.92 (m, 3H); 2.94 (s, 3H); 2.81 (dd, J = 3.6, 9.2 Hz, IH); 2.64-2.54 (m, 3H); 2.47-2.42 (m, I H); 1.98-1.90 (m, IH); 1.75-1.73 (m, IH); 1.54-1.50 (m, IH); 1.24-1.20 (m, 2H). Ex 4.12: 2-(l-Benzenesulfonyl-piperidin-3-yl)-N-methyl-7V-morpholin-4 -yl-acetamide IH NMR: (CDCl ₃ , 400 MHz) δ 7.76-7.74 (m, 2H); 7.59-7.57 (m, IH); 7.54-7.50 (m, 2H); 3.94-3.89 (m, 2H); 3.71-3.63 (m, 2H); 3.46-3.37 (m, 2H); 3.01-2.94 (m, 2H); 2.93 (s, 3H), 2.66-2.56 (m, 4H); 2.43-2.37 (m, 2H); 2.23-2.14 (m, IH); 1.75-1.72 (m, 2H); 1.66-1.58 (m, IH); 1.10-1.02 (m, IH). Ex 4.13: N-Azepan-l-yl-2-(l-benzenesulfonyl-piperidin-3-yl)-7V-methyl -acetamide

IH NMR: (CDC13, 400 MHz) δ 7.78-7.75 (m, 2H); 7.58-7.56 (m, IH); 7.54-7.50 (m, 2H); 3.54-3.45 (m, 2H); 2.92 (s, 3H); 2.94-2.82 (m, 4H); 2.61-2.44 (m, 3H); 2.35-2.30 (m, IH); 2.22-2.13 (m, IH); 1.77-1.66 (m, 9H); 1.55-1.50 (m, 2H); 1.09-0.97 (m, IH). Testing of Compounds of the invention In Vitro Cell-Based Assay CHOK-I cells were transfected with full length human 11 beta HSDl cDNA and stable transfectants generated under G418 pressure were propagated and expanded in HAM'S F- 12 (Hi Media cat No =AT085 ) supplemented with 10% NBCS (Hyclone cat No: SH30118.03) and penstrep (Sigma: P0781). One day prior to the assay, CHO- hl lbeta HSDl cells were seeded in 24 well plate at a cell density of 1,20,000 cells /well and kept overnight at 37 ⁰ C in 5% CO ₂ humidified incubator. The following day, medium from the cells were removed, cells were washed with serum free medium and 186μl of complete Ham's medium containing serially diluted 11 beta HSDl compounds dissolved in DMSO were added. The final DMSO concentration was 2%. After one hour preincubation 20OnM cortisone (Sigma: Cat No. C2755) and 0.25mM NADPH (Sigma: Cat No.N1630) were added for a period of 4h. The media from each well is collected and stored at -70 ⁰ C. Cells were then washed with PBS (phosphate bufferes saline, Sigma Cat No. D5652) and lysed with lysis buffer containing 0.1N HCL + 0.1%Triton XlOO, (Sigma Cat No. T9284) and protein was estimated following Bradford method. Quantitation of Cortisol in cell media was performed by competitive ELlSA using assay design Cortisol ELISA kit (Assay design inc.Cat No : 901-071) following manufacturer's protocol.

The results obtained from the above test using representative compounds of the formula (I) as the test compound are summarized in the following tables:

Testing of Compounds of the invention In Vitro Cell-Based Assay

CHOK-I cells were transfected with full length mouse 1 1 beta HSDl cDNA and stable transfectants generated under G418 pressure were propagated and expanded in HAM'S F- 12 (Hi Media cat No =AT085 ) supplemented with 10% NBCS (Hyclone cat No: SH301 18.03) and penstrep (Sigma: P0781). One day prior to the assay, CHO- ml lbeta HSDl cells were seeded in 24 well plate at a cell density of 1 ,20,000 cells /well and kept overnight at 37 ⁰ C in 5% CO ₂ humidified incubator. The following day, medium from the cells were removed, cells were washed with serum free medium and 186μl of complete Ham'S medium containing serially diluted 1 1 beta HSDl compounds dissolved in DMSO were added. The final DMSO concentration was 2%. After one hour preincubation 20OnM cortisone (Sigma: Cat No. C2755) and 0.25mM NADPH (Sigma: Cat No.N1630) were added for a period of 4h. The media from each well is collected and stored at -70 ⁰ C. Cells were then washed with PBS (phosphate bufferes saline, Sigma Cat No. D5652) and lysed with lysis buffer containing 0.1 N HCL + 0.1%Triton XlOO, (Sigma Cat No. T9284) and protein was estimated following Bradford method.

Quantitation of Cortisol in cell media was performed by competitive ELISA using assay design Cortisol ELISA kit (Assay design inc.Cat No : 901-071) following manufacturer's protocol.

The results obtained from the above test using representative compounds of the formula (I) as the test compound are summarized in the following table:

The novel compounds of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients by techniques and processes and concentrations as are well known. Preferably, the composition is in unit dosage form containing an effective amount of the active component, that is, the compounds of formula (1) according to this invention. The compounds of the present invention (T) inhibit l l β-HSDl and are useful in the treatment of disease states mediated by 11 β-HSDl .