Patent ID: 6416733
Filing Date: 2002-07-09
Classification: A61K,C07C,C07D,C07F

Abstract:
A compound having the formula:Weâ€”Xâ€”Lnâ€”Yâ€”Lnâ€²â€”Ch, Weâ€”Xâ€”Ln(Lnâ€²â€”Ch)â€”Y, or Zâ€”Lnâ€²â€”Ch, wherein,We is selected from the group: â€ƒwherein, A1 is N, Câ€”OH, or CH; A2 and A3 are CH; A4 is CR3; A5 is O; A6 is O, or CH2; R1 is selected from the group: H, â€”C(&boxH;NH)NH2, C1-C6 alkyl substituted with 0-2 R4, C1-C6 alkoxy substituted with 0-2 R4, aryl substituted with 0-2 R5, and heterocycle substituted with 0-2 R5; R2 is selected from the group: H, C1-C3 alkyl, C2-C3 alkenyl, cyclopropyl, cyclopropylmethyl, and aryl substituted with 0-2 R5; R3 is â€”H, â€”OH or C1-C3 alkoxy; or alternatively, R1 and R3 can be taken together with the atoms to which they are attached to form a fused phenyl ring substituted with 0-2 R5; R4 is independently selected from the group: &boxH;O, and â€”N(R6)(R7); R5 is independently selected from the group: â€”F, C1-C3 alkyl, C1-C3 alkoxy, and methylenedioxy; R6 and R7 are independently H or C1-C3 alkyl; provided that when A1 and A2 are CH, A3 is Câ€”X, and A4 is CR3, R1 is selected from the group: C1-C5 alkyl substituted with 1-3 R4, C1-C5 alkoxy substituted with 0-3 R4, and aryl substituted with 0-3 R5; X is O, CH2 or CH&boxH;CH; Ln is a linking group having the formula (CR8R9)gâˆ’(W1)hâˆ’(M1)kâˆ’(CR10R11)g, â€ƒwherein, R8, R9, R10 and R11 are independently selected at each occurrence from the group: a bond to Lnâ€², H, and C1-C3 alkylor R10 and R11 may be taken together to form a 3-6 membered cycloalkyl or heterocycle; W1 is O; M1 is selected from the group: phenyl substituted with 0-1 R12, heterocycle substituted with 0-1 R12, benzophenone substituted with 0-1 R12, and diphenylether substituted with 0-1 R12; R12 is independently selected from the group: a bond to Lnâ€², â€”COOR13, C1-C5 alkyl substituted with 0-1 R14, and C1-C5 alkoxy substituted with 0-1 R14; R13 is H or C1-C5 alkyl: R14 is independently selected from the group: a bond to Lnâ€², and â€”COOH; g is 0-10; h is 0-3; k is 0-1; g is 0-5; provided that when h is 0 and k is 0, g is >1; and provided that when W1 is O or S and k is 0, g+gâ€² is &gE;1; Y is selected from C(&boxH;O)NH, NHC(&boxH;O), C&boxH;O, C(&boxH;O)O, OC(&boxH;O), NHS(&boxH;O)2, C(&boxH;O)NHS(&boxH;O)2, COOH, C(&boxH;O)NH2, NH(C&boxH;O)NH, or tetrazole; provided that from 0-1 of R9, R10, R11, R12, and R14 is a bond to Lnâ€² and when one of these variables is a bond to Lnâ€² then Y is COOH, C(&boxH;O)NH2, or tetrazole; Lnâ€² is a linking group having the formula: (W2)hâ€²âˆ’(CR15R16)gâ€³âˆ’(M2)kâ€²âˆ’(W2)hâ€³â€”(CR17R18)gâ€³â€²âˆ’(W2)hâ€³â€²â€ƒwherein, W2 is independently selected at each occurrence from the group: O, S, NH, NHC(&boxH;O), C(&boxH;O)NH, C(&boxH;O), C(&boxH;O)O, OC(&boxH;O), NHC(&boxH;O)NH, SO2, (OCH2CH2)s, (CH2CH2O)sâ€², (OCH2CH2CH2)sâ€³, (CH2CH2CH2O)t, and (aa)tâ€², wherein aa is independently at each occurrence an amino acid, and s, sâ€², sâ€³, t, and tâ€² are independently 1-10; M2 is selected from the group: aryl substituted with 0-1 R19, cycloalkyl substituted with 0-3 R19, and heterocycle substituted with 0-1 R19; R15, R16, R17 and R18 are independently selected at each occurrence from the group: &boxH;O, COOH, SO3H, PO3H, C1-C5 alkyl substituted with 0-3 R19, aryl substituted with 0-3 R19, benzyl substituted with 0-3 R19, and C1-C5 alkoxy substituted with 0-3 R19, NHC(&boxH;O)R20, C(&boxH;O)NHR20, NHC(&boxH;O)NHR20, NHR20, R20, and a bond to Ch; R19 is independently selected at each occurrence from the group: COOR20, OH, NHR20, SO3H, PO3H, aryl substituted with 0-3 R20, heterocycle substituted with 0-3 R20, C1-C5 alkyl substituted with 0-1 R21, C1-C5 alkoxy substituted with 0-1 R21, and a bond to Ch; R20 is independently selected at each occurrence from the group: H, aryl substituted with 0-1 R21, heterocycle substituted with 0-1 R21, cycloalkyl substituted with 0-1 R21, polyalkylene glycol substituted with 0-1 R21, carbohydrate substituted with 0-1 R21, cyclodextrin substituted with 0-1 R21, amino acid substituted with 0-1 R21, polycarboxyalkyl substituted with 0-1 R21, polyazaalkyl substituted with 0-1 R21, peptide substituted with 0-1 R21, wherein said peptide is comprised of 2-10 amino acids, and a bond to Ch; R21 is a bond to Ch; kâ€² is 0-2; hâ€² is 0-2; hâ€³ is 0-5; hâ€³â€² is 0-2; gâ€³ is 0-10; gâ€³â€² is 0-10; Ch is a metal bonding unit having a formula selected from the group: Ch is selected from: â€ƒwherein, Q1 and Q4 are SH or S(Pg); Q2 and Q3 are NR22; E is independently selected from the group: CHR27, CH2CHR27, CH2CH2CHR27, and CHR27C(&boxH;O); R22 is selected from the group: H, C1-C6 alkyl substituted with 0-1 R27; and R27 are independently selected from H and a bond to Lnâ€², and, â€ƒwherein, Q1 is NH2 or N&boxH;C(R30)(R31); E is a bond; Q2 is NR22 or, NHR23, wherein R23 is heterocycle substituted with R27, wherein the heterocycle is selected from pyridine and thiazole, R27 is selected from C(&boxH;O)NHR28 and C(&boxH;O)R28, and R28 is a bond to Lnâ€²; R22 is H; R30 is selected from the group: â€”CO2R35, C2-C3 1-alkene substituted with 0-1 R34, aryl substituted with 0-1 R34, and unsaturated heterocycle substituted with 0-1 R34; R31 is H; R34 is independently selected at each occurrence from the group: â€”CO2R34, â€”OR34, â€”SO3H, and â€”N(R34)2; R35 is independently selected at each occurrence from the group: hydrogen, and methyl; A10 is NR41; R39 is C1-C10 alkoxy substituted with 1 R44; and R45 is independently selected at each occurrence from the group: OH, C(&boxH;O)OH, â€”Cl, â€”F, and NH2; Z is selected from the group: â€ƒwherein, A10 is NR41 or â€”C(R41)&boxH;CHâ€”; R37 is selected from the group: C(&boxH;O)â€”R42, CH&boxH;CR43C(&boxH;O)â€”R42, CH2C(&boxH;O)â€”R42, and CH2CH2C(&boxH;O)â€”R42; R38 is selected from the group: SR44, SCH2R44, and S(&boxH;O)R44; R39 is selected from the group: C1-C10 alkyl substituted with 0-3 R44, and C1-C10 alkoxy substituted with 0-3 R44; R40 is C(&boxH;O)â€”R42; R41 is CH2C(&boxH;O)N(CH3)CH2CH2C6H5; R42 is a bond to Lnâ€²; R43 is selected from the group: H and C1-C3 alkyl R44 is phenyl substituted with 0-4 R45; R45 is independently selected at each occurrence from the group: OR46, C(&boxH;O)OR46, â€”Cl, â€”Br, â€”F, and N(R46)2; R46 is independently selected at each occurrence from the group: H, and C1-C10 alkyl; and e indicates the position of an optional double bond; and pharmaceutically acceptable salts thereof.