Patent ID: 6524554
Filing Date: 2003-02-25
Classification: A61K,A61P,C07K

Abstract:
A compound having the formula:Châ€”Lnâ€”(X1X2X3X4X5)d, wherein:X1 is an amino acid independently selected from the group: threonine, serine, 3-hydroxyproline, and 4-hydroxyproline; X2 is an amino acid independently selected from the group: lysine, ornithine, arginine, 2-aminoethylcysteine, and glutamine; X3 and X4 are amino acids independently selected at each occurrence from the group: proline, and homoproline; X5 is an amino acid independently selected from the group: lysine, ornithine, arginine, glutamine, and 2-amino-5-(2-imidazolin-2-ylamino)pentanoic acid; d is selected from 1, 2, and 3; Ln is a linking group having the formula: (CR6R7)gâ€”(W)hâ€”(CR6aR7a)gâ€²â€”(W)hâ€²â€”(CR8R9)gâ€³â€”(W)hâ€³â€”(CR8aR9a)gâ€²â€³â€”(W)hâ€²â€³W is independently selected at each occurrence from the group: O, NH, NHC(&boxH;O), C(&boxH;O)NH, C(&boxH;O), C(&boxH;O)O, OC(&boxH;O); R6, R6a, R7, R7a, R8, R8a, R9 and R9a are independently selected at each occurrence from the group: &boxH;O, COOH, SO3H, 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, NHC(&boxH;O)R11, C(&boxH;O)NHR11, NHC(&boxH;O)NHR11, NHR11, R11, and a bond to Ch; R10 is independently selected at each occurrence from the group: a bond to Ch, COOR11, OH, NHR11, SO3H, PO3H, aryl substituted with 0-3 R11, C1-5 alkyl substituted with 0-1 R12, C1-5 alkoxy substituted with 0-1 R12, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R11; R11 is independently selected at each occurrence from the group: H, aryl substituted with 0-1 R12, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-1 R12, C3-10 cycloalkyl substituted with 0-1 R12, and a bond to Ch; R12 is a bond to Ch; h is selected from 0, 1, 2, 3, 4, and 5; hâ€² is selected from 0, 1, 2, 3, 4, and 5; hâ€³ is selected from 0, 1, 2, 3, 4, and 5; hâ€²â€³ is selected from 0, 1, 2, 3, 4, and 5; g is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; gâ€² is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; gâ€³ is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; gâ€²â€³ is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; Ch is a metal bonding unit having the formula: R13R14Nâ€”NR15R16; wherein:R13, and R14 are each independently selected from the group: hydrogen, aryl substituted with 0-3 R17, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R17; R15 and R16 are both H, or combine to form &boxH;C(R20)(R21); R17 is independently selected at each occurrence from the group: a bond to Ln, F, Cl, Br, I, â€”CF3, â€”CN, â€”CO2R18, â€”C(&boxH;O)R18, â€”C(&boxH;O)N(R18)2, â€”CH2OR18, â€”OC(&boxH;O)R18, â€”OC(&boxH;O)OR18, â€”OR18, â€”SO2N(R18)2, C1-C5 alkyl, aryl substituted with 0-2 R18, and a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O; R18 is independently selected at each occurrence from the group: a bond to Ln, H, C1-C6 alkyl, phenyl, and benzyl; R20 and R21 are independently selected from the group: H, C1-C10 alkyl, â€”CN, â€”CO2R25, â€”C(&boxH;O)R25, â€”C(&boxH;O)N(R25)2, C2-C10 1-alkene substituted with 0-3 R23, C2-C10 1-alkyne substituted with 0-3 R23, aryl substituted with 0-3 R23, unsaturated 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted substituted with 0-3 R23, and unsaturated C3-10 carbocycle substituted with 0-3 R23; alternatively, R20 and R21, taken together with the divalent carbon radical to which they are attached form: R22 and R23 are independently selected from the group: H, R24, C1-C10 alkyl substituted with 0-3 R24, C2-C10 alkenyl substituted with 0-3 R24, C2-C10 alkynyl substituted with 0-3 R24, aryl substituted with 0-3 R24, a 5-10 membered heterocyclic ring system containing 1-4 heteroatoms independently selected from N, S, and O and substituted with 0-3 R24, and C3-10 carbocycle substituted with 0-3 R24; 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: &boxH;O, F, Cl, Br, I, â€”CF3, â€”CN, â€”CO2R25, â€”C(&boxH;O)R25, â€”C(&boxH;O)N(R25)2, â€”N(R25)3+, â€”CH2OR25, â€”OC(&boxH;O)R25, â€”OC(&boxH;O)OR25a, â€”OR25, â€”OC(&boxH;O)N(R25)2, â€”NR26C(&boxH;O)R25, â€”NR26C(&boxH;O)OR25a, â€”NR26C(&boxH;O)N(R25)2, â€”NR26SO2N(R25)2, â€”NR26SO2R25a, â€”SO3H, â€”SO2R25a, â€”SR25, â€”S(&boxH;O)R25a, â€”SO2N(R25)2, â€”N(R25)2, &boxH;NOR25, â€”C(&boxH;O)NHOR25, â€”OCH2CO2H, and 2-(1-morpholino)ethoxy; and, R25, R25a, and R26 are each independently selected at each occurrence from the group: hydrogen and C1-C6 alkyl; and a pharmaceutically acceptable salt thereof.