C3-C6 alkenyl, C3-C7 cycloalkyl, C4-C11 cycloalkylalkyl, aryl, aryl (C1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy) carbonyl, and arylcarbonyl, or alternatively, when substituents on adjacent atoms, R4d and R5d can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or non-aromatic ring system, said carbocyclic or heterocyclic ring being optionally substituted with 0-2 groups selected from: C1-C4 alkyl, C1-C4 alkoxy, halo, cyano, amino, CF3, and N02; Ud is selected from: - (CH2) nd-, - (CH2) nd (CR7d=CR8d) (CH2) md~ t - (CH2) nd (C) (CH2) md-, - (CH2) tdQ (CH2) md-.

-(CH2) ndO (CH2) md~ -(CH2)ndN(R6d)(CH2)md-, - (CH2) ndC (=O) (CH2) md~x -(CH2)nd(C=O)N(R6d)(CH2)md- -(CH2)ndN(R6d)(C=O)(CH2)md-,and - (CH2) ndS (O) pd (CH2) md- ; wherein one or more of the methylene groups in Ud is optionally substituted with R7d; Qd is selected from 1,2-cycloalkylene, 1,2-phenylene, 1,3-phenylene, 1,4-phenylene, 2,3-pyridinylene, 3,4- pyridinylene, 2,4-pyridinylene, and 3,4- pyridazinylene;

R6d is selected from: H, C1-C4 alkyl, and benzyl; R7d and R8d are independently selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C4-C1l cycloalkylalkyl, aryl, aryl (Ci-Ce alkyl)-, and heteroaryl (Co-C6 alkyl)- ; R10d is selected from: H, Ride, Ci-C4 alkoxy substituted with 0-1 R21d, N(R6d)2, halogen, NO2, CN, CF3, CO2R17d, C(=O)R17d, CoNR17dR20d,-S02Rl7d, -So2NR17dR20dt Cl-C6 alkyl substituted with 0-1 R15d or 0-1 R21d, C3-C6 alkenyl substituted with 0-1 R15d or 0-1 R21d, C3-C7 cycloalkyl substituted with 0-1 R15d or 0-1 R21d, C4-C1l cycloalkylalkyl substituted with 0-1 R15d or 0-1 R21dt aryl substituted with 0-1 R15d or 0-2 R11d or 0-1 R21d, and aryl (Ci-C6 alkyl)- substituted with 0-1 R15d or 0-2 Rlld or 0-1 R21d; R10de is selected from: H, C1-C4 alkoxy substituted with 0-1 R21d, N(R6d)2, halogen, N02, CN, CF3, CO2R17d, C(=O)R17, CONR17dR20d, -SO2R17d, -SO2NR17dR20d, C1-C6 alkyl substituted with 0-1 R15d or 0-1 R21dt C3-C6 alkenyl substituted with 0-1 R15d or 0-1 R21dt ¬3-07 cycloalkyl substituted with 0-1 R15d or 0-1 R2ld, C4-C1l cycloalkylalkyl substituted with 0-1 R15d or 0-1 R2ld, aryl substituted with 0-1 R15d or 0-2 Rlld or 0-1 R21d, and aryl (C1-C6 alkyl)-substituted with 0-1 R15d or 0-2 Rlld or 0-1 R21d ;

Rlld is selected from H, halogen, CF3, CN, N02, hydroxy, NR2dR3d, Cl-C4 alkyl substituted with 0-1 R21dt Ci-C4 alkoxy substituted with 0-1 R21dt aryl substituted with 0-1 R2ld, aryl (C1-C6 alkyl)-substituted with 0-1 R21d, (Cl-C4 alkoxy) carbonyl substituted with 0-1 R21dt (C1-C4 alkyl) carbonyl substituted with 0-1 R2ld, Ci-C4 alkylsulfonyl substituted with 0-1 R21dt and C1-C4 alkylaminosulfonyl substituted with 0-1 R2 Wd is selected from: - (C (Rl2d) 2) qdC (=o) N (Rl3d)-and -C(=O)-N(R13d)-(C(R12d)2)qd-; Xd is -C(R12d)(R14d)-C(R12d)(R15d)-; or alternatively, Wd and Xd can be taken together to be R12d is selected from H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C4-C10 cycloalkylalkyl, (C1-C4 alkyl) carbonyl, aryl, and aryl (C1-C6 alkyl)- ; R13d is selected from H, C1-C6 alkyl, C3-C7 cycloalkylmethyl, and aryl (C1-C6 alkyl)- ; R14d is selected from: H, Cl-C6 alkylthio (C1-C6 alkyl)-, aryl (C1-C1o alkylthioalkyl)-, aryl (C1-Clo alkoxyalkyl)-, C1-Clo alkyl, C1-Clo alkoxyalkyl, C1-C6 hydroxyalkyl, C2-Clo

alkenyl, C2-Clo alkynyl, C3-Clo cycloalkyl, C3-Clo cycloalkylalkyl, aryl (C1-C6 alkyl)-, heteroaryl (C1-C6 alkyl)-, aryl, heteroaryl, CO2R17d, C(=O)R17d, and CONR17dR20d, provided that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 0-1 R16d or 0-2 Rlld ; R15d is selected from: H, R16dt C1-Clo alkyl, C1-Clo alkoxyalkyl, C1-Clo alkylaminoalkyl, C1-C10 dialkylaminoalkyl, (Cl-Clo alkyl) carbonyl, aryl (C1-C6 alkyl) carbonyl, Cl-calo alkenyl, Cl-Cl0 alkynyl, C3-C10 cycloalkyl, C3- Clo cycloalkylalkyl, aryl (C1-C6 alkyl)-, heteroaryl (C1-C6 alkyl)-, aryl, heteroaryl, C02Rl7d, C(=O)R17d, CONR17dR20d, SO2R17d, and SO2NR17dR20d, provided that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 0-2 R11d; Yd is selected from: -COR19d,-SO3H,-PO3H, tetrazolyl,-CONHNHS02CF3,- CONHSO2R17d, -CONHSO2NHR17d, -NHCOCF3, -NHCONHSO2R17d, -NHS02R17d,-OP03H2,-OS03H,-P03H2,-S03H,- SO2NHCOR17d, -SO2NHCO2R17d, R16d is selected from:

-N(R20d)-C(=O)-O-R17d, -N(R20d)-C(=O)-R17d, -N (R20d)-c (-0)-NH-Rl7d -N (R20d) So2-Rl7dt and -N (R20d) S02-NR20dRl7d ; R17d is selected from: Cl-Clo alkyl optionally substituted with a bond to Ln, C3-C11 cycloalkyl optionally substituted with a bond to Ln, aryl (Cl-C6 alkyl)-optionally substituted with a bond to Ln, (Cl-C6 alkyl) aryl optionally substituted with a bond to Ln, heteroaryl (C1-C6 alkyl)-optionally substituted with a bond to Ln, (C1-C6 alkyl) heteroaryl optionally substituted with a bond to Ln, biaryl (C1-C6 alkyl)-optionally substituted with a bond to Ln, heteroaryl optionally substituted with a bond to Ln, aryl optionally substituted with a bond to Ln, biaryl optionally substituted with a bond to Ln, and a bond to Ln, wherein said aryl, biaryl or heteroaryl groups are also optionally substituted with 0-3 substituents selected from the group consisting of: C1-C4 alkyl, C1-C4 alkoxy, aryl, heteroaryl, halo, cyano, amino, CF3, and N02; R18d is selected from: -H, -C(=O)-O-R17d, -C(=0)-Rl7d, -C(=O)-NH-R17d, -S02-Rl7d, and -SO2-NR20dR17d;

R19d is selected from: hydroxy, Cl-Clo alkyloxy, C3-C11 cycloalkyloxy, aryloxy, aryl (C1-C6 alkoxy)-, C3-Clo alkylcarbonyloxyalkyloxy, C3-C1o alkoxycarbonyloxyalkyloxy, C2-Clo alkoxycarbonylalkyloxy, C5-Clo cycloalkylcarbonyloxyalkyloxy, C5-Clo cycloalkoxycarbonyloxyalkyloxy, C5-C10 cycloalkoxycarbonylalkyloxy, C7-C1l aryloxycarbonylalkyloxy, C8-C12 aryloxycarbonyloxyalkyloxy, C8-C12 arylcarbonyloxyalkyloxy, C5-Clo alkoxyalkylcarbonyloxyalkyloxy, C5-Clo (5-alkyl-1,3-dioxa-cyclopenten-2-one- yl) methyloxy, C1o-Cl4 (5-aryl-1,3-dioxa-cyclopenten- 2-one-yl) methyloxy, and (Rlld) (Rl2d) N-(cl-clo alkoxy)-; R20d is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C4-C11 cycloalkylalkyl, aryl, aryl (C1-C6 alkyl)-, and heteroaryl (C1-C6 alkyl)- ; R21d is selected from: COOH and NR6d2; d m is 0-4; d n is 0-4; d t is 0-4; d p is 0-2; d q is 0-2; and d r is 0-2;

provided that at least one Q is a compound of Formula (Ia) or (Ib); d is selected from 1,2,3,4,5,6,7,8,9, and 10; d'is 1-100; Ln is a linking group having the formula: ( (W) h- (CR6R7) g) - (Z) k- ( (CR6ap7a) g,- (W) h') x' ; W is independently selected at each occurrence from the group: 0, S, NH, NHC(=O), C (=O)NH, NR8C(=O), C(=O)N R8, C (=O), C(=O)O, OC(=O), NHC (=S) NH, NHC (=O) NH, SO2, S02NH, (OCH2CH2) S, (CH2CH20) s', (OCH2CH2CH2) s".

(CH2CH2CH20) t, and (aa) t' aa is independently at each occurrence an amino acid; Z is selected from the group: aryl substituted with 0-3 R10, C3-10 cycloalkyl substituted with 0-3 R10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0 and substituted with 0-3 R10; R6, R6a, R7, R7a, and R8 are independently selected at each occurrence from the group: H, =O, COOH, S03H, P03H, Cl-C5 alkyl substituted with 0-3 R10, aryl substituted with 0-3 R10, benzyl substituted with 0-3 R10, and C1-C5 alkoxy substituted with 0-3 R10, NHC (=O) Rll, C(=O)NHR¹¹, NHC(=O)NHR¹¹, NHR¹¹, R¹¹, and a bond to Ch;

substituted with 0-3 R17, heterocyclo-C1-lo alkyl substituted with 0-3 R17, wherein the heterocyclo group is a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0, C6-10 aryl-C1-lo alkyl substituted with 0-3 R17, C1_lo alkyl-C6-1o aryl-substituted with 0-3 R17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0 and substituted with 0-3 R17; R17 is independently selected at each occurrence from the group: a bond to Ln, =0, F, Cl, Br, I,-CF3,-CN, -CO2R18, -C(=O)R18, -C(=O)N(R18)2, -CHO, -CH2OR18, -OC(=O)R18, -OC(=O)OR18a, -OR18, -OC(=O)N(R18)2, -NR19C (=O) -NR19C(=O)N(R18)2, -NR19So2N (Rl8) 2-NR19So2Rl8at-S03H,-SO2R18a, -SR18, -S(=O)R18a, -SO2N(R18)2, -N(R18)2, -NHC (=S) NHR18, =NOR18, N02, -C(=O)NHOR18, -C (=O) NHNR18Rl8a,-OCH2CO2H, 2- (l-morpholino) ethoxy, Ci-C5 alkyl, C2-C4 alkenyl, C3-C6 cycloalkyl, C3-C6 cycloalkylmethyl, C2-C6 alkoxyalkyl, aryl substituted with 0-2 R18, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0; R18, Rl8a, and R19 are independently selected at each occurrence from the group: a bond to Ln, H, C1-C6 alkyl, phenyl, benzyl, C1-C6 alkoxy, halide, nitro, cyano, and trifluoromethyl;

alternatively, R22, R23 taken together form a fused aromatic or a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O; a and b indicate the positions of optional double bonds and n is 0 or 1; R24 is independently selected at each occurrence from the group: =O, F, Cl, Br, I,-CF3,-CN,-C02R25, -C (=0) R25,-C (=o) N (R25) 2,-N (R25) 3+,-CH20R25, -OC (=0) R25, -OC (=O)OR25a, -OR25, -OC(=O)N(R25)2, -NR26C (=0) R25,-NR26C (=0) OR25a,-NR26C (=O) N (R25) 2, -NR26SO2N(R25)2, -NR26SO2R25a, -SO3H, -SO2R25a, -SR25, -S(=O)R25a, -SO2N(R25)2, -N(R25)2, =NOR25, -C (=0) NHOR25,-OCH2C02H, and 2- (1-morpholino) ethoxy; and, R25, R25a, and R26 are each independently selected at each occurrence from the group: hydrogen and Cl-C6 alkyl.

3 In a more preferred embodiment, the present invention provides a compound wherein: Ride is selected from:

<BR> Ad and Bd are independently-CH2-,-0-,-N (R2d)-, or-C (=0)- ; A1d and B1d are independently-CH2-or-N (R3d)-; D is-N (R2d)-,-O-,-S-,-C (=O)-or-SO2-;

<BR> <BR> Ed-Fd is -C(R4d)=C(R5d)-, -N=C (R4d)-,-C (R4d) =N-, or- C (R4d) 2C (R5d) 2- ; d d d d J, K, L and M are independently selected from: C (R4d)-,-C (R5d)-and-N-, provided that at least one d d d d of J, K, L and M is not-N- ; R2d is selected from: H, C1-C6 alkyl, (Cl-C6 alkyl) carbonyl, (C1-C6 alkoxy) carbonyl, C1-C6 alkylaminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C4-C11 cycloalkylalkyl, aryl, heteroaryl (Cl-C6 alkyl) carbonyl, heteroarylcarbonyl, aryl (C1-C6 alkyl)-, (C1-C6 alkyl) carbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, aryl (Cl-C6 alkyl) sulfonyl, heteroarylsulfonyl, heteroaryl (Cl-C6 alkyl) sulfonyl, aryloxycarbonyl, and aryl (Cl-C6 alkoxy) carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C1-C4 alkyl, Cl-C4 alkoxy, halo, CF3, and nitro; R3d is selected from: H, C1-Cg alkyl, C3-C7 cycloalkyl, Cq-C11 cycloalkylalkyl, aryl, aryl (Cl-C6 alkyl)-, and heteroaryl (C1-C6 alkyl)- ; R4d and R5d are independently selected from: H, C1-C4 alkoxy, NR2dR3d, halogen, N02, CN, CF3, Cl-C6 alkyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C4-Cll cycloalkylalkyl, aryl, aryl (Cl-C6 alkyl)-, C2-C7 alkylcarbonyl, and arylcarbonyl;

R7d and R8d are independently selected from: H, Cl-C6 alkyl, C3-C7 cycloalkyl, C4-C1l cycloalkylalkyl, aryl, aryl (Cl-C6 alkyl)-, and heteroaryl (C0-C6 alkyl)- ; <BR> <BR> <BR> <BR> <BR> <BR> Wd is-C(=O)-N(R13d)-(C(R12d)2)qd-; X is-C (R12d) (Rl4d)-c (Rl2d) (Rl5d)- ; d d alternatively, W and X can be taken together to be R12d is H or Ci-Ce alkyl; d Yd is selected from: -COR19d, SO3H, d is selected from 1,2,3,4, and 5; d'is 1-50;

W is independently selected at each occurrence from the group: 0, NH, NHC (=O), C (=O)NH, NR8C(=O), C (=O)N R8, C(=O), C (=O)O, OC =O), NHC (=S) NH, NHC (=O) NH, S02, (OCH2CH2) s. (CH2CH20) 5t, (OCH2CH2CH2) s". (CH2CH2CH20) t, and (aa) t,; aa is independently at each occurrence an amino acid; Z is selected from the group: aryl substituted with 0-1 R10, C3-. 10 cycloalkyl substituted with 0-1 R10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0 and substituted with 0-1 R10 ; R6, R6a, R7, R7a, and R8 are independently selected at each occurrence from the group: H, =0, COOH, S03H, C1-C5 alkyl substituted with 0-1 R10, aryl substituted with 0-1 R10, benzyl substituted with 0-1 R10, and Ci-C5 alkoxy substituted with 0-1 R10, NHC (=O) Rll, C(=O)NHR¹¹, NHC(=O)NHR¹¹, NHR¹¹, R¹¹, and a bond to Ch; k is 0 or 1; s is selected from 3,4, and 5; s'is selected from 0,1,2,3,4, and 5; s"is selected from 0,1,2,3,4, and 5; t is selected from 0,1,2,3,4, and 5; A1, A2, A3, A4, A5, A6, A7, and A8 are independently selected at each occurrence from the group: NR¹³, NR13Rl4, S, SH, S (Pg), OH, and a bond to Ln;

E is a bond, CH, or a spacer group independently selected at each occurrence from the group: C1-Clo alkyl substituted with 0-3 R17, aryl substituted with 0-3 R17, C3-10 cycloalkyl substituted with 0-3 R17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0 and substituted with 0-3 R17; R13 and R14 are each independently selected from the group: a bond to Ln, hydrogen, C1-Clo alkyl substituted with 0-3 R17, aryl substituted with 0-3 R17, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0 and substituted with 0-3 R17, and an electron, provided that when one of R13 or R14 is an electron, then the other is also an electron; alternatively, R13 and R14 combine to form =C(R20)(R21); R17 is independently selected at each occurrence from the group: a bond to Ln, =0, F, Cl, Br, I,-CF3,-CN, -CO2R18,-C (=O) R18,-C(=O)N(R18)2, -CH2OR18, -OC(=O)R18, -OC(=O)OR18a, -OR18, -OC(=O)N(R18)2, -NR19C (=O) Rl8,-NR19C (=0) -NR19C(=O)N(R18)2, -NR19So2N (Rl8) 2,-NR19S02Rl8a,-S03H,-S02R18a, -S (=O) R18a,-SO2N (R18) 2,-N (R18) 2,-NHC (=S) NHR18, =NOR18,-C(=O)NHNR18R18a, -OCH2CO2H, and 2-(1-morpholino)ethoxy;

wherein the above heterocycles are optionally substituted with 0-2 substituents selected from the group: NH2, halogen, N02, CN, CF3, Ci-C4 alkoxy, C1-C6 alkyl, and C3-C7 cycloalkyl; d d d d d Ud is - (CH2)n-, -(CH2)tdQd (CH2)md- or -C(=O)(CH2)nd-1-, wherein one of the methylene groups is optionally substituted with R7d; 7d R is selected from: C1-C6 alkyl, C3-C7 cycloalkyl, C4- Cll cycloalkylalkyl, aryl, aryl (C1-C6 alkyl), heteroaryl, and heteroaryl (Cl-C6 alkyl); R10d is selected from: H, Rude, Cl-C4 alkoxy substituted with 0-1 R21dt halogen, CO2R17d, CONR17dR20d, C1-C6 alkyl substituted with 0-1 R15d or 0-1 R,¬3-07 cycloalkyl substituted with 0-1 R15d or 0-1 R21d, C4-Cll cycloalkylalkyl substituted with 0-1 R15d or 0-1 R2ld, and aryl (C1-C6 alkyl)-substituted with 0-1 R15d or 0-2 Rlld or 0-1 R21d ; RlOde is selected from: H, Ci-C4 alkoxy substituted with 0-1 R21dt halogen, CO2R17d, CONR17dR20d, C1-C6 alkyl substituted with 0-1 R15d or 0-1 R21d C3-C7 cycloalkyl substituted with 0-1 R15d or 0-1 R21dt C4-Cll cycloalkylalkyl substituted with 0-1 R15d or 0-1 R21dt and aryl (Cl-C6 alkyl)-substituted with 0-1 R15d or 0-2 R11d or 0-1 R21d; W is-C (=0)-N (Rl3d)- ;

<BR> Xd is-CH (Rl4d)-CH (Rl5d)-; i R13 is H or CH3; R14d is selected from: H, C1-Clo alkyl, aryl, or heteroaryl, wherein said aryl or heteroaryl groups are optionally substituted with 0-3 substituents selected from the group consisting of: Ci-C4 alkyl, Cl-C4 alkoxy, aryl, halo, cyano, amino, CF3, and N02; Rl5d is H or R16d ; <BR> <BR> <BR> <BR> <BR> <BR> d<BR> <BR> Y is-CORl9d ; R19d is selected from: hydroxy, C1-Clo alkoxy, methylcarbonyloxymethoxy-, ethylcarbonyloxymethoxy-, t-butylcarbonyloxymethoxy-, cyclohexylcarbonyloxymethoxy-, 1- (methylcarbonyloxy) ethoxy-, 1- (ethylcarbonyloxy) ethoxy-, 1- (t-butylcarbonyloxy) ethoxy-, 1- (cyclohexylcarbonyloxy) ethoxy-, i-propyloxycarbonyloxymethoxy-, t-butyloxycarbonyloxymethoxy-, 1- (i-propyloxycarbonyloxy) ethoxy-, 1- (cyclohexyloxycarbonyloxy) ethoxy-, 1- (t-butyloxycarbonyloxy) ethoxy-, dimethylaminoethoxy-, diethylaminoethoxy-,

2-(((4-(3-(N-(3-(2-(2-(3-(2-(1,4,7,10-tetraaza-4,7,10- tris(carboxymethyl)cyclododecylacetylamino)-6- aminohexanoylamino)propoxy)ethoxy)ethoxy)propyl)- carbamoyl) propoxy)-2,6-dimethylphenyl)- sulfonyl) amino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonylamino)- propionic acid salt;

2- ( { 4- (3- {N- 2- ( (2R)-3-Sulfo-2- {2- 1,4,7,10-tetraaza- 4,7,10-tris (carboxymethyl) cyclododecyl acetylamino}-

propyl)ethyl carbamoyllpropoxy)-2, 6-dimethylphenyl- sulfonyl} amino) (2S)-3- ( {1- 3- (imidazol-2- ylamino) propyl (lH-indazol-5- yl)} carbonylamino) propanoic Acid; 2- (f4- 4- ( { 2- ( (2R)-3-Sulfo-2- {2- 1,4,7,10-tetraaza- 4,7,10-tris (carboxymethyl) cyclododecyl- acetylamino} propyl) ethyl amino} sulfonyl) phenyl pheny l} sulfonyl) amino] (2S)-3- ( {l- 3- (imidazol-2- ylamino) propyl (lH-indazol-5- yl)} carbonylamino) propanoic Acid; (4S)-4-(N-{1-[N-(2-{4-[4-({[(1S)-1-carboxy-2-({1-[3-(2- pyridylamino)propyl](1H-indazol-5- yl)}carbonylamino)ethylamino}sulfonyl)-3,5- dimethylphenoxy butanoylamino} ethyl) carbamoyl]-3- carboxypropyl} carbamoyl)-4- {2- 1,4,7,10-tetraaza- 4,7,10- tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid; (4S)-4-(N-{1-[N-(2-{4-[4-({[(1S)-1-carboxy-2-({1-[3- (imidazol-2-ylamino)propyl](1H-indazol-5- yl)}carbonylamino)ethylamino}sulfonyl)-3,5-

dimethylphenoxy butanoylamino} ethyl) carbamoyl-3- carboxypropyl} carbamoyl)-4-2- 1,4,7,10-tetraaza- 4,7,10- tris (carboxymethyl) cyclododecyl] acetylamino} butanoic acid; (4S)-4-{N-(lS)-1-(N-{1,3-bis N- (2-14- 4- (I (lS)-l- carboxy-2- ( {l- 3- (imidazol-2-ylamino) propyl (lH- indazol-5-yl)} carbonylamino) ethyl] amino} sulfonyl)- 3,5- dimethylphenoxy butanoylamino} ethyl) carbamoyl propyl } carbamoyl)-3-carboxypropyl carbamoyl}-4- (6- {2- 1,4,7,10-tetraaza-4,7,10- tris (carboxymethyl) cyclododecyl acetylamino} hexanoylamino) butanoic acid ; (4S)-4- (N- {l- N- (2- {4- 4- ( { (lS)-l-carboxy-2- ( {l- 3- (3,4,5,6-tetrahydropyrimidin-2-ylamino) propyl (lH- indazol-5-yl)} carbonylamino) ethyl amino} sulfonyl)- 3,5-dimethylphenoxy] butanoylamino} ethyl) carbamoyl- 3-carboxy propyl} carbamoyl)-4- {2- 1,4,7,10-tetraaza- 4,7,10-tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid; (4S)-4-(N-{1-[N-(2-{4-[4-({[(1S)-1-carboxy-2-({1-methyl- 3-[3-(2-3,4,5,6-tetrahydropyridylamino)propyl][3-(2-3,4,5,6- tetrahydropyridylamino)propyl] (1H- indazol-6-yl)} carbonylamino) ethyl] amino} sulfonyl)- 3,5-dimethylphenoxy] butanoylamino} ethyl) carbamoyl]- 3-carboxypropyl} carbamoyl)-4- {2- 1,4,7,10-tetraaza- 4,7,10- tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid;

(4S)-4-(N-{(1S)-1-[N-(2-{4-[4-({[(1S)-1-carboxy-2-({1-[2- (2-3,4,5,6-tetrahydropyridylamino)ethyl] (1H- indazol-5-yl)} carbonylamino) ethyl] amino} sulfonyl)- 3,5-dimethylphenoxy] butanoylamino} ethyl) carbamoyl- 3-carboxy propyl} carbamoyl)-4- {2- 1,4,7,10-tetraaza- 4,7,10-tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid; (2S)-2-{[(2,6-dimethyl-4-{3-[N-(2-{2-[1,4,7,10-tetraaza- 4,7,10-tris(carboxymethyl)cyclododecyl]acetyl- amino}ethyl)carbamoylpropoxy}phenyl)sulfonylamino} -3- ( {2- 2- (2-3,4,5,6- tetrahydropyridylamino) ethyl] (2-hydro-lH-indazol-5- yl)} carbonylamino) propanoic acid; (4S)-4- {N- (lS)-l- (N- {2- ( {4- 4- ( { (lS)-l-carboxy-2- ( {l- 2- (2-3,4,5,6-tetrahydropyridylamino) ethyl] (1H- indazol-5- yl)} carbonylamino) ethyl amino} sulfonyl) phenyl phenyl} sulfonyl) amino ethyl} carbamoyl)-3- carboxypropyl] carbamoyl}-4-{2-[1,4,7,10-tetraaza- 4,7,10-tris-(carboxy- methyl)cyclododecyl]acetylamino}butanoic acid; (4S)-4-{N-(lS)-1-(N-{2-({4-4-({(lS)-1-carboxy-2-({1- 3- (3,4,5,6-tetrahydropyrimidin-2-ylamino) propyl (lH-indazol-5- yl)} carbonylamino) ethyl] amino} sulfonyl) phenyl phenyl} sulfonyl) amino ethyl} carbamoyl)-3- carboxy propyl carbamoyl}-4- {2- 1,4,7,10-tetraaza- 4,7,10-tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid;

99mTc ( ( ( (4- (4- ( ( (3- (2- (2- (3- ( (6- (diazenido) (3- pyridyl)) carbonylamino) propoxy)- ethoxy) ethoxy) propyl) amino) sulfonyl)- phenyl) phenyl) sulfonyl) amino)-3- ( (l- (3- (imidazole-2- ylamino) propyl) (lH-indazol-5- yl)) carbonylamino) propanoic acid) (tricine) (TPPTS); 99mTc (2- (2- ( (5- (N- (1,3-bis (3-(2-(2-(3-(((4-(4-(((1- carboxy-2- ( (l- (3- (imidazol-2-ylamino) propyl) (lH- indazol-5-yl)) carbonylamino) ethyl) amino) sulfonyl)- phenyl) phenyl) sulfonyl) amino) propoxy)- ethoxy) ethoxy) propyl) carbamoyl) propyl) carbamoyl) (2- pyridyl)) 2-diazenido) (tricine) (TPPTS); 99mTc (2- ( (6- (diazenido) (3-pyridyl)) carbonylamino)-4- (N- (3- (2- (2- (3- ( ( (4- (4- ( ( (l-carboxy-2- ( (l- (3- (imidazol- 2-ylamino) propyl) (lH-indazol-5-yl)) carbonylamino)- ethyl) amino) sulfonyl) phenyl) phenyl) sulfonyl)- amino) propoxy)- ethoxy) ethoxy) propyl) carbamoyl) butanoic acid) (tricine) (TPPTS); 99mTc (2- (6- ( (6- (diazenido) (3- pyridyl)) carbonylamino) hexanoylamino)-3- ( (l- (3- (imidazol-2-ylamino) propyl) (lH-indazol-5- yl)) carbonylamino)-propanoic acid) (tricine) (TPPTS); 99mTc (2-((6-(diazenido)(3-pyridyl))carbonylamino)-3-((1- (3-(imidazol-2-ylamino)propyl) (1H-indazol-5- yl))carbonylamino)propanoic acid (tricine) (TPPTS); 99mTc 2- 5- carbonyl-2-pyridinyl diazenido-Glu (2- (6- aminohexanoylamino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonyl-

[19] In another preferred embodiment wherein the metallopharmaceutical is a therapeutic radiopharmaceutical, the metal is a radioisotope selected from the group: 186Re, 188Re, 153Sm, 166Ho, 177Lu, 149Pm, 90Y, ²¹²Bi, 103Pd, 109Pd, 159Gd, 140La, 198Au, 199Au, 169Yb, 175Yb, 165Dy, 166Dy, 67Cu, 105Rh, lllAg, and 192Ir, the targeting moiety is an indazole nonpeptide and the linking group is present between the targeting moiety and chelator.

[20] In another preferred embodiment, the targeting moiety is an indazole and the receptor is (X, P3 or avés.

21 In another preferred embodiment, the radioisotope is 153Sm.

Ald and Bld are independently-CH2-or-N (R3d)-; Dd is-N (R2d)-,-O-,-S-,-C (=0)-or-S02- ; Ed-Fd is -C (R4d)=C(R5d)-, -N=C(R4d)-, -C(R4d)=N-,(R4d)=C(R5d)-, -N=C(R4d)-, -C(R4d)=N-, or - C(R4d)2C(R5d)2-; Jd, Kd, Ld and Md are independently selected from: -C (R4d)-,-C (R5d)-and-N-, provided that at least one of Jd, Kd, Ld and Md is not-N- ; R2d is selected from: H, Cl-C6 alkyl, (C1-C6 alkyl) carbonyl, (C1-C6 alkoxy) carbonyl; (C1-C6 alkyl) aminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl, Cq-C11 cycloalkylalkyl, aryl, heteroaryl (C1-C6 alkyl) carbonyl, heteroarylcarbonyl, aryl (C1-C6 alkyl)-, (C1-C6 alkyl) carbonyl-, arylcarbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, aryl (C1-C6 alkyl) sulfonyl, heteroarylsulfonyl, heteroaryl (C1-C6 alkyl) sulfonyl, aryloxycarbonyl, and aryl (C1-C6 alkoxy) carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C1-C4 alkyl, Ci-C4 alkoxy, halo, CF3, and nitro; R3d is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, Cq-C11 cycloalkylalkyl, aryl, aryl (Ci-Ce alkyl)-, and heteroaryl (C1-C6 alkyl)- ; R4d and R5d are independently selected from: H, C1-C4 alkoxy, NR2dR3d, halogen, NO2, CN, CF3, Cl-C6 alkyl,

C3-C6 alkenyl, C3-C7 cycloalkyl, Cq-C11 cycloalkylalkyl, aryl, aryl (C1-C6 alkyl)-, (Cl-C6 alkyl) carbonyl, (C1-C6 alkoxy) carbonyl, arylcarbonyl, or alternatively, when substituents on adjacent atoms, R4d and R5d can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or non-aromatic ring system, said carbocyclic or heterocyclic ring being optionally substituted with 0-2 groups selected from: C1-C4 alkyl, C1-C4 alkoxy, halo, cyano, amino, CF3, and N02; Ud is selected from: - (CH2) n-, -(CH2)nd(CR7d=CR8d)(CH2)md-, -(CH2)nd(C#C)(CH2)md-, - (CH2) tdQ (CH2) md-r -(CH2)ndO(CH2)md-, - (CH2) ndN (R6d) (CH2) m -(CH2) ndC (=3) (CH2) md-w -(CH2)nd(C=O)N(R6d)(CH2)md- -(CH2)ndN(R6d)(C=O)(CH2)md-, and - (CH2) nS (0) pd (CH2)- ; wherein one or more of the methylene groups in Ud is optionally substituted with R7d; Qd is selected from 1,2-cycloalkylene, 1,2-phenylene, 1,3-phenylene, 1,4-phenylene, 2,3-pyridinylene, 3,4-

pyridinylene, 2,4-pyridinylene, and 3,4- pyridazinylene; R6d is selected from: H, C1-C4 alkyl, or benzyl; R7d and R8d are independently selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C4-Cll cycloalkylalkyl, aryl, aryl (C1-C6 alkyl)-, and heteroaryl (Co-C6 alkyl)- ; R10d is selected from: H, Rude, Ci-C4 alkoxy substituted with 0-1 R21d, N(R6d)2, halogen, N02, CN, CF3, C02Rl7d, C (=O) Rl7d, CONR17dR20d,-S02Rl7d,- SO2NR17dR20d, C1-C6 alkyl substituted with 0-1 R15d or 0-1 R21dt C3-C6 alkenyl substituted with 0-1 R15d or 0-1 R21dt C3-C7 cycloalkyl substituted with 0-1 R15d or 0-1 R21dt C4-C1l cycloalkylalkyl substituted with 0-1 R15d or 0-1 R21dt aryl substituted with 0-1 R15d or 0-2 Rlld or 0-1 R2ld, and aryl (Cl-C6 alkyl)- substituted with 0-1 R15d or 0-2 R11d or 0-1 R21d; Rôde is selected from: H, Ci-C4 alkoxy substituted with 0-1 R21d, N(R6d)2, halogen, N02, CN, CF3, C02Rl7d, C(=O)R17d, CONR17dR20D, -SO2R17d, -SO2NR17dR20d, C1-C6 alkyl substituted with 0-1 R15d or 0-1 R21d, C3-C6 alkenyl substituted with 0-1 R15d or 0-1 R21d, ¬3-07 cycloalkyl substituted with 0-1 R15d or 0-1 R21dt Cq-C11 cycloalkylalkyl substituted with 0-1 R15d or 0-1 R21dt aryl substituted with 0-1 R15d or 0-2 Rlld or 0-1 R2ld, and aryl (C1-C6 alkyl)-substituted with 0-1 R15d or 0-2 Rlld or 0-1 R21d;

Rlld is selected from H, halogen, CF3, CN, N02, hydroxy, NR2dR3d, Ci-C4 alkyl substituted with 0-1 R2ldCi-C4 alkoxy substituted with 0-1 R21d, aryl substituted with 0-1 R21dt aryl (C1-C6 alkyl)-substituted with 0-1 R21dt (Cl-C4 alkoxy) carbonyl substituted with 0-1 R21dt (C1-C4 alkyl) carbonyl substituted with 0-1 R21dt Ci-C4 alkylsulfonyl substituted with 0-1 R21d, and Ci-C4 alkylaminosulfonyl substituted with 0-1 R21d Wd is selected from: -(C(R12d)2)qdC(=O)N(R13d)-,and -C(=O)-N (Rl3d)- (C (Rl2d) 2) qd- ; Xd is-C (Rl2d) (Rl4d)-c (Rl2d) (Rl5d)-; or alternatively, Wd and Xd can be taken together to be R12d is selected from H, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C4-C10 cycloalkylalkyl, (Cl-C4 alkyl) carbonyl, aryl, and aryl (C1-C6 alkyl)- ; R13d is selected from H, Ci-Ce alkyl, C3-C7 cycloalkylmethyl, and aryl (C1-C6 alkyl)- ; R14d is selected from:

H, C1-C6 alkylthio (C1-C6 alkyl)-, aryl (C1-Clo alkylthioalkyl)-, aryl (C1-Clo alkoxyalkyl)-, C1-Clo alkyl, C1-Clo alkoxyalkyl, C1-C6 hydroxyalkyl, C2-C1o alkenyl, C2-Clo alkynyl, C3-C10 cycloalkyl, C3-Clo cycloalkylalkyl, aryl (C1-C6 alkyl)-, heteroaryl (C1-C6 alkyl)-, aryl, heteroaryl, C02Rl7d, C (=0) R17d, and CONR17dR20d, provided that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 0-1 R16d or 0-2 Rlld ; R15d is selected from: H, R16d, C1-Clo alkyl, C1-Clo alkoxyalkyl, C1-Clo alkylaminoalkyl, C1-C10 dialkylaminoalkyl, (C1-C10 alkyl)carbonyl, aryl(C1-C6 alkyl)carbonyl, Cl-calo alkenyl, Cl-Clo alkynyl, C3-Clo cycloalkyl, C3- Clo cycloalkylalkyl, aryl (Ci-Ce alkyl)-, heteroaryl (C1-C6 alkyl)-, aryl, heteroaryl, C02Rl7d, C(=O)R17d, CoNRl7dR20dt SO2R17d, and SO2NR17dR20d, provided that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 0-2 Rlld ; Yd is selected from: -CORl9d,-S03H,-P03H, tetrazolyl,-CONHNHS02CF3,- CONHSO2R17d, -CONHSO2NHR17d, -NHCOCF3, -NHCONHSO2R17d, -NHSO2R17d, -OPO3H2, -OSO3H, -PO3H2, -SO3H, - SO2NHCOR17d, -SO2NHCO2R17d,

R16d is selected from: -N(R20d)-C(=O)-O-R17d, -N (R20d)-c (=o)-Rl7dt -N(R20d)-C(=O)-NH-R17d, -N (R20d) S02-Rl7d, and -N (R20d) s02-NR20dRl7d ; R17d is selected from: Ci-Cio alkyl optionally substituted with a bond to Ln, C3-C11 cycloalkyl optionally substituted with a bond to Ln, aryl (Cl-C6 alkyl)-optionally substituted with a bond to Ln, (C1-C6 alkyl) aryl optionally substituted with a bond to Ln, heteroaryl (C1-C6 alkyl)-optionally substituted with a bond to Ln, (Cl-C6 alkyl) heteroaryl optionally substituted with a bond to Ln, biaryl (C1-C6 alkyl)-optionally substituted with a bond to Ln, heteroaryl optionally substituted with a bond to Ln, aryl optionally substituted with a bond to Ln, biaryl optionally substituted with a bond to Ln, and a bond to Ln, wherein said aryl, biaryl or heteroaryl groups are also optionally substituted with 0-3 substituents selected from the group: C1-C4 alkyl, Cl-C4 alkoxy, aryl, heteroaryl, halo, cyano, amino, CF3, and N02; R18d is selected from: -H,

-C(=O)-O-R17d, -C(=O)-R17d, -C (=O)-NH-Rl7d, -S02-Rl7d, and -SO2-NR20dR17d; R19d is selected from: hydroxy, C1-Clo alkyloxy, C3-C11 cycloalkyloxy, aryloxy, aryl (C1-C6 alkoxy)-, C3-Clo alkylcarbonyloxyalkyloxy, C3-Clo alkoxycarbonyloxyalkyloxy, C2-Clo alkoxycarbonylalkyloxy, Cs-Cio cycloalkylcarbonyloxyalkyloxy, C5-Clo cycloalkoxycarbonyloxyalkyloxy, Cs-Clo cycloalkoxycarbonylalkyloxy, Cy-Cn aryloxycarbonylalkyloxy, Cg-C12 aryloxycarbonyloxyalkyloxy, Ce'Ci2 arylcarbonyloxyalkyloxy, C5-Clo alkoxyalkylcarbonyloxyalkyloxy, C5-Clo (5-alkyl-1,3-dioxa-cyclopenten-2-one- yl) methyloxy, C10-C14 (5-aryl-1,3-dioxa-cyclopenten- 2-one-yl)methyloxy, and (Rlld) (Rl2d) N-(Cl-Clo alkoxy)-; R20d is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, Cq-C11 cycloalkylalkyl, aryl, aryl (Ci-C6 alkyl)-, and heteroaryl (C1-C6 alkyl)- ; R21d is selected from: COOH and NR6d2; d m is 0-4; d n is 0-4; d t is 0-4;

provided that one of R1 and R2 in each Q is substituted with a bond to Ln, and further provided that when R2 is 2-aminothiazole-4-acetic acid, K is N-methylarginine; provided that at least one Q is a compound of Formula Ia or Ib; d is selected from 1,2,3,4,5,6,7,8,9, and 10; Ln is a linking group having the formula: ( (W) h- (CR6R7) g- (Z) k- ( (CR6aR7a) g,- (w) h') ; W is independently selected at each occurrence from the group: 0, S, NH, NHC (=O), C (=O) NH, NR8C(=O), C(=O)N R8, C (=O), C(=O)O, OC(=O), NHC (=S)NH, NHC (=O)NH, SO2, S02NH, (OCH2CH2) 20-200, (CH2CH20) 2o-2oOs (OCH2CH2CH2) 20- 200, (CH2CH2CH20)20-200, and (aa)t'; aa is independently at each occurrence an amino acid; Z is selected from the group: aryl substituted with 0-3 R10, C3-10 cycloalkyl substituted with 0-3 R10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0 and substituted with 0-3 R10; R6, R6a, R7, R7a, and R8 are independently selected at each occurrence from the group: H, =0, COOH, S03H, PO3H, C1-C5 alkyl substituted with 0-3 R10, aryl substituted with 0-3 R10, benzyl substituted with 0-3 R10, and C1-C5 alkoxy substituted with 0-3 R10, Rlde is selected from:

Ad and Bd are independently-CH2-,-0-,-N (R2d)-, or-C (=0)- ; Ald and Bld are independently-CH2-or-N (R3d)- ; Dd is -N(R2d)-, -O-, -S-, -C(=O)- or -SO2-;

<BR> <BR> Ed-Fd is -C (R4d)=C(R5d)-, -N=C(R4d)-, -C(R4d)=N-, or - C(R4d)2C(R5d)2-; d d d d J, K, L and M are independently selected from: -C (R4d)-,-C (R5d)-and-N-, provided that at least d d d d one of J, K, L and M is not-N- ; R2d is selected from: H, C1-C6 alkyl, (C1-C6 alkyl)carbonyl, (Cl-C6 alkoxy) carbonyl, C1-C6 alkylaminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C4-C1l cycloalkylalkyl, aryl, heteroaryl (C1-C6 alkyl) carbonyl, heteroarylcarbonyl, aryl (C1-C6 alkyl)-, (C1-Cg alkyl) carbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, aryl (C1-C6 alkyl) sulfonyl, heteroarylsulfonyl, heteroaryl (C1-C6 alkyl) sulfonyl, aryloxycarbonyl, and aryl (C1-C6 alkoxy) carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group: Ci-C4 alkyl, Cl-C4 alkoxy, halo, CF3, and nitro; R3d is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C4-C1l cycloalkylalkyl, aryl, aryl (Ci-C6 alkyl)-, and heteroaryl (Ci-C6 alkyl)- ; R4d and R5d are independently selected from: H, C1-C4 alkoxy, NR2dR3d, halogen, N02, CN, CF3, Cl-C6 alkyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C4-C1l cycloalkylalkyl, aryl, aryl (C1-C6 alkyl)-, C2-C7 alkylcarbonyl, and arylcarbonyl or

aryl, aryl (C1-C6 alkyl)-, and heteroaryl (C0-C6 alkyl)-; <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> Wd is-C(=O)-N(R13d)-(C(R12d)2)qd-;<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> Xd is -C(R12d)(R14d)-C(R12d)(R15d)-; d d alternatively, W and X can be taken together to be

R12d is H or Ci-Ce alkyl; d Y is selected from: -CoR19dt-SO3H,

Z is selected from the group: aryl substituted with 0-1 R10, C3-10 cycloalkyl substituted with 0-1 R10, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and 0 and substituted with 0-1 R10 ; R6, R6a, R7, R7a, and R8 are independently selected at each occurrence from the group: H, =0, COOH, SO3H,

C1-C5 alkyl substituted with 0-1 R10, aryl substituted with 0-1 R10, benzyl substituted with 0-1 R10, and C1-C5 alkoxy substituted with 0-1 R10, NHC (=O) R1l, C(=O)NHR11, NHC(=O)NHR11, NHR11, R11, and a bond to Sf ; k is 0 or 1; Sf is a surfactant which is a lipid or a compound of the formula: A9 is OR27; A10 is OR27; R27 is C (=O) C1-15 alkyl; E1 is C1-4 alkylene substituted with 1-3 R28; R28 is independently selected at each occurrence from the group: R30,-Po3H-R30, =O,-C02R29,-C (=0) R29, -CH2OR29, -OR29, and C1-C5 alkyl; R29 is independently selected at each occurrence from the group: R30, H, C1-C6 alkyl, phenyl, and benzyl; R30 is a bond to Ln; and a pharmaceutically acceptable salt thereof.

dimethylformamide (2 mL). Triethylamine (18.5 uL, 0.133 mmol) was added, and the reaction was stirred for 5 min.

2- 5- (2, 5-Dioxo-l-pyrrolidinyl) oxy] carbonyl-2- pyridinyl hydrazono-methyl-benzenesulfonic acid, monosodium salt (0.0234 g, 0.0532 mmol) was added, and the reaction was stirred for 4 days. The reaction was concentrated to an oil under high vacuum. The oil was purified by Preparative HPLC Method A to give 33.7 mgs (97%) of product. HRMS: Calcd. for C36H41N11°8S + H, 788.2938; Found, 788.2955.

Analytical HPLC, Method B, Rt = 14.06 min, Purity = 90% Example 6 Synthesis of 2- ( (6- ( (l-Aza-2- (2-sulfophenyl) vinyl)- amino) (3-pyridyl)) carbonylamino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonylamino) propanoic acid 2-Amino-3- ( (l- (3- (imidazol-2-ylamino) propyl) (lH- indazol-5-yl)) carbonylamino) propanoic acid (0.025 g, 0.0515 mmol) was dissolved in N, N-dimethylformamide (2 mL). Triethylamine (21.5 µL, 0.154 mmol) was added, and the reaction was stirred for 5 min. 2- 5- (2,5-Dioxo- 1-pyrrolidinyl) oxy carbonyl-2-pyridinyl hydrazono- methyl-benzenesulfonic acid, monosodium salt (0. 0272 g,

0.0515 mmol) was added, and the reaction was stirred under nitrogen for 18 h. The reaction mixture was concentrated to an oil under high vacuum. The oil was purified by preparative HPLC using Preparative HPLC Method A to give 14.6 mgs (42%) of the desired product.

ESMS: Calcd. for C30H30N10O7S, 674.20; Found, 697.1 M+Na +1.

Analytical HPLC, Method B, Rt = 13.48 min, Purity = 95% Example 7 Synthesis of 2- 5- carbonyl-2- pyridinyl hydrazono methyl]-benzenesulfonic acid]-Glu (2- (6-Aminohexanoylamino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonyl-amino) propanoic acid)(2- (6-aminohexanoylamino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonyl-amino) propanoic acid) Part A. Preparation of Boc-Glu (OSu)-OSu

Glu (2- (6-Aminohexanoylamino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonyl-amino) propanoic acid) (2- (6-Aminohexanoylamino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonyl-amino) propanoic acid) (0.0481 mmol) is dissolved in DMF (2 mL).

Triethylamine (20.1 uL, 0.144 mmol) is added, and after 5 min of stirring 2-[[[5-[[(2,5-dioxo-1- pyrrolidinyl)oxy]carbonyl]-2-pyridinyl]hydrazono]- methyl]-benzenesulfonic acid, monosodium salt (0.0254 g, 0.0577 mmol) is added. The reaction mixture is stirred for 20 h and then concentrated to an oil under high vacuum. The oil is purified by preparative RP-HPLC to obtain the desired product.

Example 8 Synthesis of 2- 5- carbonyl-2- pyridinyl hydrazono methyl]-benzenesulfonic acid]-Glu- bis-[Glu (2-(6-Aminohexanoylamino)-3- (3-(imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonyl-amino) propanoic acid) (2- (6-Aminohexanoylamino)-3- ( (l- (3- (imidazol-2- ylamino) propyl) (lH-indazol-5-yl)) carbonyl-amino) propanoic acid)]

Part A. Preparation of 2- (1,4,7,10-tetraaza-4,7,10- tris (t-butoxycarbonylmethyl)-1-cyclododecyl) acetyl-Glu {2- (6-Aminohexanoylamino)-3-((1-(3-(imidazol-2- ylamino)propyl)(1H-indazol-5-yl))carbonyl-amino)propanoic acid}{2-(6-Aminohexanoylamino)-3-((1-(3-(imidazol-2- ylamino)propyl)(1H-indazol-5-yl))carbonyl-amino)propanoic acid}

with ACN to give the title compound (45.5 g, 73.0%) in purified form. MS: m/e 566.0 M+Na.

Part B-Preparation of 2-{[(4-{3-[N-(2-{(2R)-2-[4-(N- {(1R)-1-N-(2-{4-4-({(1S)-1-carboxy-2-({1-3-(imidazol- 2-ylamino)propyl](1H-indazol-5-yl)}carbonylamino)- ethyl amino} sulfonyl)-3, 5-dimethylphenoxy butanoylamino}- ethyl)carbamoyl-2-sulfoethyl} carbamoyl) (4S)-4-(tert- butoxy) carbonylamino] butanoylamino-3-sulfopropyl} ethyl)- carbamoyl propoxy}-2,6-dimethylphenyl) sulfonyl amino} 2S)- 3- ( (1- 3- (imidazol-2-ylamino) propyl (1H-indazol-5- yl)} carbonylamino) propanoic Acid A solution of the product of Example 34, Part F (43,5 mg, 0.0459 mmol), the product of Part A, above (10.8 mg, 0.020 mmol), and DIEA 0.015 mL, 0.084 mmol) in anhydrous DMF (1.0 mL) was stirred at ambient temperatures under nitrogen for 23 h. The DMF was removed under vacuum and the resulting amber oil was purified by HPLC on a Vydac C-18 column (22 x 250 mm) using a 0.90%/min gradient of 9 to 45% ACN containing

0.1% TFA at a flow rate of 20 mL/min. The main product peak eluting at 20.9 min was lyophilized to give the title compound as a colorless fluffy solid (22.0 mg, 55.7%). MS: m/e 1880.7 [M+H], 941.4 [M+2H]; High Resolution MS: Calcd for C78H1o6N2lo26S4 M+H: 1880.6501; found: 1880.6530.

Part C-Preparation of 2-{[(4-{3-[N-(2-{(2R)-2-[4-(N- {(1R)-1-N-(2-{4-4-({(1S)-1-carboxy-2-({1-3-(imidazol- 2-ylamino)propyl](1H-indazol-5-yl)}carbonylamino)- ethyl amino} sulfonyl)-3, 5-dimethylphenoxy butanoylamino}- ethyl) carbamoyl-2-sulfoethyl} carbamoyl) (4S)-4-amino- butanoylamino-3-sulfopropyl} ethyl) carbamoyl propoxy}- 2,6-dimethylphenyl) sulfonyllaminol2S)-3- (fl- 3- (imidazol- 2-ylamino) propyl] (lH-indazol-5- yl)} carbonylamino) propanoic Acid A solution of the product of Part B, above (22.0 mg, 0.0117 mmol) in 50/50 TFA/DCM (8.0 mL) was allowed to react at ambient temperatures under nitrogen for 10 min and concentrated to a pale amber oil. The oil was dissolved in 50% ACN (20 mL) and lyophilized to give the

title compound as a colorless fluffy solid (21.2 mg, 95.6%). MS: m/e 1781.7 [M+H], 891.0 [M+2H], 594. 4 M+3H; High Resolution MS: Calcd for C73H98N21024S4 M+H : 1780.5976; found: 1780.598.

Part D-Preparation of DOTA Tris-t-butyl Ester/2-{(4- {3-[N-(2-{(2R)-2-[4-(N-{(1R)-1-[N-(2-{4-[4-({[(1S)-1- carboxy-2-({1-[3-(imidazol-2-ylamino)propyl]({1-[3-(imidazol -2-ylamino)propyl] (H-indazol- 5-yl))carbonylamino)ethylamino}sulfonyl)-3,5- dimethylphenoxy butanoylamino} ethyl) carbamoyl]-2- sulfoethyl} carbamoyl) (4S)-4-aminobutanoylamino-3- sulfopropyl} ethyl) carbamoyl propoxy}-2,6-dimethylphenyl)- sulfonyl] amino} 2S)-3- ( {1- 3- (imidazol-2- ylamino) propyl] (lH-indazol-5-yl)} carbonylamino) propanoic Acid Bis (trifluoroacetate) Salt Conjugate A solution of the product of Example 4, Part B (21.4 mg, 0.0234 mmol), DIEA (0.024 mL, 0.14 mmol), and HBTU (6.6 mg, 0.0176 mmol) in anhydrous DMF (1.0 mL) was stirred under nitrogen at ambient temperatures for 15 min and treated with the product of Part C, above 21.0 mg, 0.0111 mmol). After 23 h the solution was diluted with

Resolution MS: Calcd for C89Hl24N25o3lS4 M+H: 2166.7778; Found: 2166.778.

Example 36 Synthesis of 2- ( {4- 4- ( { 2- ( (2R)-3-Sulfo-2- {2- 1,4,7,10- tetraaza-4,7,10-tris (carboxymethyl) cyclododecyl- acetylamino} propyl) ethyl amino} sulfonyl) phenyl phenyl}- sulfonyl) amino] (2S)-3- ( {l- 3- (imidazol-2- ylamino) propyl (lH-indazol-5-yl)} carbonylamino) propanoic Acid Bis (trifluoroacetate) Salt

Part A-Preparation of Methyl (2S)-3-(tert- Butoxy)carbonylamino]-2-{[(4-{4-[({2-[(phenylmethoxy)- carbonylamino]ethyl}amino)sulfonyl]phenyl}phenyl)sulfonyl amino}propanoate

Biphenyl-4,4'-disulfonyl chloride (5.30 g, 15.0 mmol, freshly recrystallized from CHC13) and DCM (400 mL) were placed in a 100 mL 3-neck flask fitted with a thermometer, an addition funnel, and a nitrogen line.

The addition funnel was charged with a solution of benzyl N- (2-aminoethyl) carbamate hydrochloride (2.30 g, 10.0 mmol) and DIEA (1.80 mL, 10.0 mmol) in DCM (40 mL). The contents of the flask were cooled below 5 °C, and the

was added and stirring was continued an additional 24 h.

The DMF was removed under vacuum and the oily solid residue was purified by HPLC on a Vydac C-18 column (22 x 250 mm) using a 1.12%/min gradient of 18 to 63% ACN containing 0.1% TFA at a flow rate of 20 mL/min. The main product peak was centered at 32.1 min. The earliest eluting product fractions contained an impurity which was removed by HPLC purification with the same column and flow conditions, but using a 1.0%/min gradient of 18 to 58% ACN containing 0.1% TFA. The main product peak eluted at 32.1 min. The product containing fractions from these two runs were combined and lyophilized to give the title compound as a colorless solid (174 mg, 65.6% from the product of Part C). MS: m/e 1217.3 [M+H], 1117.3 [M+H-Boc].

Part F-Preparation of 2- ( {4- 4- (f 2- ( (2R)-2-Amino-3- sulfopropyl) ethyl amino} sulfonyl) phenyl] phenyl} sulfonyl) a mino (2S)-3- ( {1- 3- (imidazol-2-ylamino) propyl] (lH- indazol-5-yl)} carbonylamino) propanoic Acid Trifluoroacetate Salt A mixture of the product of Part E, above (21.4 mg, 0.0176 mmol), peroxide-free THF (0.70 mL), water (0.063 mL), and 3 N LiOH (0.043 mL, 0.129 mmol) was stirred at ambient temperatures under nitrogen for 3 h, and concentrated under vacuum to a colorless solid.

The above solid was dissolved in 95/5 TFA/Et3SiH (1.20 mL) and heated at reflux under nitrogen for 1 h.

In dry glassware under nitrogen were mixed HBTU (35 mg, 90 umol), DOTA (OtBu) 3-OH (49 mg, 85 umol), and diisopropylethylamine (35 uL, 200 umol) in dry DMF (7 mL). This was stirred for 10 minutes and then the product of step E (100 mg, 77 umol) was added, along with additional diisopropylethylamine (45 uL, 250 umol) to bring solution pH>9. After stirring for 30 min, the reaction was concentrated and purified by preparative HPLC (Vydac C18,21.2 mm x 25 cm, 90% acetonitrile/water/0.1% TFA; 20-70% B over 50 minutes).

Four products were obtained after purification; a pair of glutamic acid isomers (60 mg) and the corresponding Boc deprotected compounds (29 mg) for a total yield of 66%.

Step G: Synthesis of 4-(N-{(1R)-1-[N-(2-{4-[4-({[(1S)-1- carboxy-2-({1-[3-(2-pyridylamino)propyl]({1-[3-(2-pyridylami no)propyl] (1H-indazol-5- yl)}carbonylamino)ethylamino}sulfonyl)-3,5- dimethylphenoxy butanoylamino} ethyl) carbamoyl]-3- carboxypropyl} carbamoyl) (4S)-4- {2- 1,4,7,10-tetraaza- 4,7,10- tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid

Step A: Synthesis of (2S)-2-{[(4-{3-[N-(2-{4-[N-(2-{4- [4-({[(1S)-1-carboxy-2-({1-[3-(imidazol-2- ylamino)propyl] (1H-indazol-5- yl)} carbonylamino) ethyl amino} sulfonyl)-3,5- dimethylphenoxy butanoylamino} ethyl) carbamoyl-4- (tert- butoxy) carbonylamino butanoylamino} ethyl) carbamoyl propox y}-2,6-dimethylphenyl) sulfonyl amino}-3- ( {l- 3- (imidazol- 2-ylamino) propyl] (lH-indazol-5- yl)} carbonylamino) propanoic acid

The product of F (10 mg) was added to dichloromethane (1 mL) containing trifluoroacetic acid (1 mL) and triethylsilane (200 uL) and stirred under nitrogen for 72 hours. The reaction was concentrated and purified by preparative HPLC (Vydac C18,21.2 mm x 25 cm, 90% acetonitrile/water/0.1% TFA; 15-55% B over 50 minutes).

The product fraction was frozen and lyophilized to afford the product as a white powder (1 mg, 15%). LRMS (ES): 1118.7 ( M + 2H+2,10%), 746.3 ( [M+3H]+3, 40%) 560.0 ( M+4H+4, 100%).

Example 40 Synthesis of (4S)-4- (N- {l- N- (2- {4- 4- ( { (lS)-l-carboxy- 2- ( {1- 3- (3,4,5,6-tetrahydropyrimidin-2- ylamino) propyl (lH-indazol-5- yl)} carbonylamino) ethyl amino} sulfonyl)-3,5- dimethylphenoxy] butanoylamino} ethyl) carbamoyl]-3-carboxy propyl} carbamoyl)-4- {2- 1,4,7,10-tetraaza-4,7,10-tris (carboxymethyl) cyclododecyl] acetylamino} butanoic acid Step A: Synthesis of ethyl 1- 3- (pyrimidin-2- ylamino)propyl-lH-indazole-5-carboxylate

was purified by preparative HPLC (Vydac C18,21.2 mm x 25 cm, 90% acetonitrile/water/0.1% TFA; 10-70% B over 30 minutes). The product fractions were frozen and lyophilized to afford the desired product as a white powder (825 mg, 88%). LRMS (ES): 844.3 ( M + H] +.

Step D: Synthesis of methyl (2S)-2-{[(4-{3-[N-(2- aminoethyl)carbamoyl]propoxy}-2,6- dimethylphenyl)sulfonyl] amino}-3-({1-3-(3,4,5,6- tetrahydropyrimidin-2-ylamino) propyl (lH-indazol-5- yl)} carbonylamino) propanoate The product of Step C (250 mg, 260 umol) was treated as in Example 37, Step B to afford the product as a white powder (220 mg, 89%). LRMS (ES): 714.3 ( M + H] +, 25%), 402.2 (30%), 357.1 ( M + 2H] +2,100%). HRMS: Calculated for C33H48N707S : 714.3397; Found : 714.3374.

Step E: Synthesis of tert-butyl (4S)-4- N- (2- {4- 4- ( { (lS)-l- (methoxycarbonyl)-2- ( {l- 3- (3,4,5,6-tetrahydro pyrimidin-2-ylamino) propyl (lH-indazol-5- yl)} carbonylamino) ethyl] amino} sulfonyl)-3,5- dimethylphenoxy butanoylamino} ethyl) carbamoyl]-4- (phenylmethoxy) carbonylamino] butanoate

79%). LRMS (ES): 899.5 ( M + H]+, 50%), 450.2 ( M + 2H] +2,65%), 422.4 ( (M-tBu) + 2H]+2, 100%).

Step G: Synthesis of tert-butyl 4-{(2S)-4-(tert- butyl) oxycarbonyl-2-(phenylmethoxy) carbonylamino butanoylamino}-4- N- (2- {4- 4- ( { (lS)-l- (methoxycarbonyl)- 2- (tl- 3- (3,4,5,6-tetrahydropyrimidin-2- ylamino) propyl (lH-indazol-5- yl)} carbonylamino) ethyl amino} sulfonyl)-3,5- dimethylphenoxy] butanoylamino} ethyl) carbamoyl butanoate The product of step F (85 mg, 76 umol) was treated as in step E to afford the product after lyophilization (87 mg, 87%). LRMS (ES): 1218.6 ( M + H] +, 100%), 610.0 ( M + 2H]+2, 20%), 581.8 ( (M-tBu) + 2H] +2,30%), 553.8 ( (M- 2tBu) + 2H +2, 85%).

Step H: Synthesis of tert-butyl (4S)-4-(N-{1-N-(2-{4- 4- ( { (lS)-l- (methoxycarbonyl)-2- ( {l- 3- (3,4,5,6- tetrahydro pyrimidin-2-ylamino) propyl (lH-indazol-5- yl)} carbonylamino) ethyl] amino} sulfonyl)-3,5- dimethylphenoxy] butanoylamino} ethyl) carbamoyl-3-(tert- butyl) oxycarbonyl propyl} carbamoyl)-4-aminobutanoate

1344.5 ( M+Hl 672.9 (M+2H +2,100%), 449.9 ([M+3H]+3, 50%).

Example 41 Synthesis of (4S)-4-(N-{1-N-(2-{4-4-({(1S)-1-carboxy- 2-({1-methyl-3-[3-(2-3,4,5,6- tetrahydropyridylamino)propyl] (1H-indazol-6- yl)} carbonylamino) ethyl amino} sulfonyl)-3,5- dimethylphenoxy] butanoylamino} ethyl) carbamoyl-3- carboxypropyl} carbamoyl)-4- {2- 1,4,7,10-tetraaza-4,7,10- tris (carboxymethyl) cyclododecyl] acetylamino} butanoic acid

Step A: Synthesis of methyl (2S)-2-[({2,6-dimethyl-4-[3- (N-{2- (phenylmethoxy)carbonylaminoethyl}carbamoyl)propoxy phenyl} sulfonyl) amino-3- ( {1-methyl-3- 3- (2-pyridylamino) propyl (1H-indazol-6-yl)}carbonylamino)propanoate

1-Methyl-3- 3- (2-pyridylamino) propyl-lH-indazole-6- carboxylic acid (79 mg, 256 umol, prepared as described

x 25 cm, 90% acetonitrile/0.1% TFA; 20-75% B over 45 minutes). The product fractions were frozen and lyophilized to afford the desired product as a white powder (62 mg, 75%). LRMS (ES): 1651.9 ( M + H] +, 5%), 826.7 ( M + 2H] +2,30%), 532.8 ( (M-tBu) + 3H] +3,25%), 514.9 ( (M-2tBu) + 3H, 100%), 495.4 ( (M-3tBu) + 3H] +3, 60%).

Step F: Synthesis of (4S)-4-(N-{1-[N-(2-{4-[4-({[(1S)-1- carboxy-2-({1-methyl-3-3-(2-3,4,5,6- tetrahydropyridylamino) propyl (1H-indazol-6- yl)} carbonylamino) ethyl amino} sulfonyl)-3,5- dimethylphenoxy butanoylamino} ethyl) carbamoyl-3- carboxypropyl} carbamoyl)-4- {2- 1,4,7,10-tetraaza-4,7,10- tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid The product of step E (42 mg, 25 umol) was treated as in Example 40, Step J and the crude product purified by preparative HPLC (Zorbax CN, 21.2 mm x 25 cm, 50% acetonitrile/water/0.1% formic acid; 20-35% B over 60 minutes). The product fractions were combined, frozen, and lyophilized to afford the product as a white solid (11 mg, 48%). LRMS (EI); 1357.6 (M+H + 15%), 679.5 (M+2H +2,100%), 453.3 (M+3H +3, 40%).

Example 42

Step I: Synthesis of tert-butyl (4S)-4-(N-{(1S)-1-[N-(2- {4-4-({(1S)-1-(methoxycarbonyl)-2-({1-2-(2-3,4,5,6- tetrahydropyridylamino)ethyl] (1H-indazol-5-yl)}carbonyl amino) ethyl] amino} sulfonyl)-3, 5-dimethylphenoxy butanoyl amino} ethyl) carbamoyl-3-[(tert-butyl) oxycarbonyl] propyl} carbamoyl)-4- 2- (1,4,7,10-tetraaza-4,7,10-tris {(tert- butyl) oxycarbonyl methyl} cyclododecyl) acetylamino butanoate The product of Step H is treated as in Example 40, Step H. The residue is not purified but coupled directly with DOTA (OtBu) 3-OH as in Example 40, step I. The product is obtained as a white solid after lyophilization.

Step J: Synthesis of (4S)-4-(N-{(1S)-1-[N-(2-{4-[4- ({(1S)-1-carboxy-2-( {1-2-(2-3,4,5,6-tetrahydropyridyl amino)ethyl](1H-indazol-5-yl)}carbonylamino)ethyl]amino} sulfonyl)-3,5-dimethylphenoxy] butanoylamino} ethyl) carbamoyl]-3-carboxy propyl} carbamoyl)-4- {2- 1,4,7,10- tetraaza-4,7,10-tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid

compound after preparative HPLC purification and lyophilization of the product fractions.

Example 44 Synthesis of (4S)-4-{N-[(1S)-1-(N-{2-[({4-[4-({[(1S)-1- carboxy-2-({1-[2-(2-3,4,5,6-tetrahydropyridylamino)ethyl] (1H-indazol-5- yl)} carbonylamino) ethyl] amino} sulfonyl) phenyl phenyl} sulfonyl) amino] ethyl} carbamoyl)-3-carboxypropyl carbamoyl}-4- {2- 1,4,7,10-tetraaza-4,7,10-tris (carboxy- methyl) cyclododecyl acetylamino} butanoic acid

Step A: Synthesis of methyl (2S)-3-amino-2-{(4-{4-({2- (phenylmethoxy) carbonylamino ethyl} amino) sulfonyl phenyl } phenyl) sulfonyl amino} propanoate

Biphenyl-4,4'-disulfonyl chloride (5.3 g, 15 mmol) was reacted with N- (2-aminoethyl) (phenylmethoxy) carboxamide (2.3 g, 10 mmol) and methyl (2S)-2-amino-3- (tert- butoxy) carbonyl amino propanoate (5.1 g, 20 mmol)

was stirred for 1 hour, concentrated and the residue purified by preparative HPLC (Zorbax C-8,21.2 mm x 25 cm, 90% acetonitrile/water/0.1% trifluoroacetic acid; 20-60% B over 40 minutes). The product fractions were combined, frozen, and lyophilized to afford the product as a white solid (102 mg, 67%). LRMS (ES): 871.3 ( M + H +, 100%). HRMS: Calculated for C4lH43N8OloS2 : 871.2544; Found : 871.2540.

Step C: Synthesis of methyl (2S)-2-({[4-(4-{[(2-amino ethyl)amino]sulfonyl}phenyl)phenyl]sulfonyl}amino)-3-({1- 2-(2-3,4,5,6-tetrahydropyridylamino)ethyl (1H-indazol-5- yl)} carbonylamino) propanoate The product of Step B (75 mg, 76 umol) was treated as in Example 41, Step B and purified by preparative HPLC (Zorbax C-8,21.2 mm x 25 cm, 90% acetonitrile/water/ 0.1% trifluoroacetic acid; 15-25% B over 40 minutes).

The product fractions were combined, frozen, and lyophilized to afford the product as a white solid (56 mg, 86%). LRMS (ES): 725.2 ( M + H] +, 20%), 363.2 (M + 2H]+2,100%).

Step D: Synthesis of tert-butyl (4S)-4- (N- {2- ( {4- 4- ( { (lS)-l- (methoxycarbonyl)-2- ( {l- 2- (2-3,4,5,6- tetrahydro pyridylamino) ethyl] (lH-indazol-5- yl)} carbonylamino) ethyl amino} sulfonyl) phenyl phenyl} sulfonyl) amino ethyl} carbamo yl}-4-[(phenylmethoxy) carbonylamino] butanoate

The product of Step C was reacted as in Example 40, Step E to afford the product as a white solid after lyophilization. LRMS Step E: Synthesis of tert-butyl (4S)-4-{(2S)-4-(tert- butyl)oxycarbonyl-2- (phenylmethoxy) carbonylamino butanoyl amino}-4-(N-{2- ({4-4-({(lS)-1-(methoxycarbonyl)-2-({1-2-(2-3,4,5,6- tetrahydropyridylamino) ethyl (lH-indazol-5-yl)} carbonylamino) ethyl] amino} sulfonyl) phenyl phenyl} sulfonyl ) amino ethyl} carbamoyl) butanoate The product of Step D is treated as in Example 40, Step F to afford the product as a white solid after lyophilization.

Step F: Synthesis of tert-butyl (4S)-4-{N-(lS)-1-(N-{2- [({4-[4-({[(1S)-1-(methoxycarbonyl)-2-({1-[2-(2-3,4,5,6- tetrahydropyridylamino)ethyl] (1H-indazol-5-yl)} carbonyl amino) ethyl] amino} sulfonyl) phenyl phenyl} sulfonyl) amino] [({4-[4-({[(1S)-1-(methoxycarbonyl)-2-({1-[3-(3,4,5,6- tetrahydropyrimidin-2-ylamino)propyl] (1H-indazol-5- yl)} carbonylamino) ethyl amino} sulfonyl) phenyl phenyl} sulf onyl) amino ethyl} carbamoyl) butanoate

The product of Step B (96 mg, 82 umol) was treated as in Example 41, Step D to afford the product as a white solid (48 mg, 42%) after lyophilization. LRMS (ES): 1244.4 ( M + H] +, 100%), 566.8 ( (M-2tBu) + 2H] +2,45%).

Step D: Synthesis of tert-butyl (4S)-4-{N-(lS)-1-(N-{2- ( {4- 4- (I (lS)-l- (methoxycarbonyl)-2- (fl- 3- (3,4,5,6- tetrahydropyrimidin-2-ylamino) propyl (lH-indazol-5-yl)} carbonylamino) ethyl amino} sulfonyl) phenyl phenyl} sulfonyl )amino ethyl} carbamoyl)-3-(tert- butyl)oxycarbonyl propyl carbamoyl}-4- 2- (1,4,7,10- tetraaza-4,7,10-tris {(tert-butyl) oxycarbonyl methyl} cyclododecyl) acetylamino] butanoate The product of Step C (47 mg, 35 umol) was treated as in Example 41, Step E to afford the product as a white solid (36 mg, 62%) after lyophilization. LRMS (ES): 1664.6

(M + H +, 5 %), 833. 2 ((M + 2H +2,60%), 518.4 ( (M- 2tBu) + 3H] +3,100%).

Step E: Synthesis of (4S)-4-N- (1S)-1- (N-2- ( {4- 4- ( ( (lS)-l-carboxy-2- (fl- 3- (3,4,5,6-tetrahydropyrimidin- 2-ylamino) propyl] (lH-indazol-5- yl)} carbonylamino) ethyl amino} sulfonyl) phenyl phenyl} sulfonyl) amino] ethyl} carbamoyl)-3- carboxypropyl] carbamoyl}-4- {2- 1,4,7,10-tetraaza-4,7,10- tris (carboxymethyl) cyclododecyl acetylamino} butanoic acid The product of Step D (29 mg, 15 umol) was treated as in Example 40, Step J to afford the crude product which was purified by preparative HPLC (Vydac C-18,21.2 mm x 25 cm, 90% acetonitrile/water/0.1% trifluoroacetic acid; 5-35% B over 35 minutes). The product fractions were combined, frozen, and lyophilized to afford the product as a white solid (11 mg, 46%) after lyophilization. LRMS (ES): 1370.4 ( M + H] +, 10 %), 685.8 ( (M + 2H] +2,90%), 457.6 ( M + 3H] +3,100%).

Example 46 Synthesis of (2S)-3-( {3-[(imidazol-2-ylamino) methyl]-1- methyl (1H-indazol-6-yl)} lcarbonylamino)-2- (f 4- (4-1 (2- {2- 1,4,7,10-tetraaza-4,7,10-tris (carboxymethyl) cyclododecyl] acetylamino} ethyl) amino] sulfonyl} phenyl) phen yl] sulfonyl} amino) propanoic acid filtered, washed with water, and dried under vacuum to afford the product.

Step D: Synthesis of

The product of Step C (190 mg, 370 umol) is reacted with the product of Example 44, Step A (285 mg, 407 umol) as in Example 44, Step B and the residue is purified by preparative HPLC (Vydac C-18,21.2 mm x 25 cm, 90% acetonitrile/water/0.1% trifluoroacetic acid; 10-70% B over 30 minutes). The product fractions are combined, frozen, and lyophilized to afford the product.

Step E: Synthesis of methyl (2S)-2-({[4-(4-{[(2-amino ethyl)amino]sulfonyl}phenyl)phenyl]sulfonyl}amino)-3-{ [1- methyl-3-({[1-(triphenylmethyl)imidazol-2- yl amino} methyl) (lH-indazol-6- yl)]carbonylamino} propanoate The product of Step D (100 mg) in methanol (10 mL) is added to a slurry of 10% palladium on carbon (50 mg) in methanol (8 mL) in a Parr bottle under nitrogen. The solution is hydrogenated at 50 psi for 1.5 hours,

filtered through Celite, washed with methanol, and the combined filtrates concentrated. The resulting oil is not purified but carried directly into the next step.

Step F: Synthesis of methyl (2S)-3-{1-methyl-3-({1- (triphenylmethyl) imidazol-2-yl amino} methyl) (lH-indazol- 6-yl) carbonylamino}-2- {[(4-{4-[({2-[2-(1, 4,7,10- tetraaza-4,7,10-tris { [ (tert- butyl)oxycarbonyl methyl} cyclododecyl) acetylamino ethyl} amino) sulfonyl phenyl} phenyl) sulfonyl] amino} propanoate The product of Step E (73 mg, 77 umol) is reacted with DOTA (OtBu) 3-OH (49 mg, 85 umol) as in Example 37, Step F, to afford the product as a pure compound after purification and lyophilization.

Step G: Synthesis of (2S)-3-({3-[(imidazol-2-ylamino) methyl-1-methyl (1H-indazol-6-yl)} carbonylamino)-2-({4- (4-1 (2-f2- 1,4,7,10-tetraaza-4,7,10-tris (carboxymethyl) cyclododecyl acetylamino} ethyl) amino] sulfonyl} phenyl) phen yl] sulfonyl} amino) propanoic acid