Patent ID: 6670373
Filing Date: 2003-12-30
Classification: A61P,C07D

Abstract:
A compound of formula I: where:het is a five (5) membered heteroaryl ring containing N and a second heteroatom selected from N, O, or S; wherein the non-fused carbon atom of the heteroaryl ring is optionally substituted with C1-C6 alkyl, aryl, aryl substituted from 1 to 3 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, N(R1)2, SO2N(R1)2, NH-Pg, C1-C6 alkoxy, benzyloxy, CO2R1, C5-C7 cycloalkyl, trifluoromethoxy, or nitro, heterocycle, heterocycle substituted 1 or 2 times independently with a C1-C6 alkyl, halo, benzyl, phenyl, or trifluoromethyl, an amino acid ester, CH2OH, CH2O-heterocycle, halo, CH2N3, CH2SR1, CH2NR4R5, OR1, SR12, S(CH2)n-phenyl, or NR4R5; provided that when het is pyrazole or imidazole, the saturated nitrogen of the het ring is optionally substituted with C1-C4 alkyl; R is (CH2)mâ€²CHR1NHR2, O(CH2)2NHR2, (CH2)mâ€²COR3, NHR2, and (CH2)mâ€²CHR1NR4R5; Râ€² is hydrogen, hydroxy, or O(C1-C6 alkyl optionally substituted with phenyl or C3-C7 cycloalkyl); m and mâ€² are independently at each occurrence 0, 1, or 2; R1 is independently at each occurrence hydrogen or C1-C6 alkyl; R2 is hydrogen, COR6, CH2R6â€², SO2R7, or a moiety of the formula R3 is hydrogen, hydroxy, C1-C6 alkoxy, an amino acid ester, an amino acid, or NR4R5, wherein the amino acid is selected from the group consisting of alanine, asparagine, cysteine, glutamine, glycine, isoleucine, leusine, methionine, phenylalanine, proline, serine threonine, tryptophan, tyrosine, valine, aspartic acid, glutamic acid, arginine, histidine, and lysine; R4 is hydrogen or C1-C6 alkyl; R5 is hydrogen, C1-C6 alkyl, C6-C10 bicycloalkyl, (C1-C4 alkyl)-phenyl, (C1-C4 alkyl)-CO2R1, CH2CO2R1, aryl, aryl substituted from 1 to 3 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, N(R1)2, SO2N(R1)2, NH-Pg, C1-C6 alkoxy, benzyloxy, CO2R1, C5-C7 cycloalkyl, trifluoromethoxy, or nitro, (CH2)nCHR8NHC(O)OC(CH3)3, (CH2)nNH2, (CH2)2NHCOR6, (CH2)2OR1, (CH2)q-heterocycle, (CH2)q (heterocycle substituted 1 or 2 times independently with a C1-C6 alkyl, halo, benzyl, phenyl, or trifluoromethyl), or R4 and R5, together with the nitrogen to which they are attached, combine to form a pyrrolidin-1-yl, piperidin-1-yl, hexamethyleneimin-1-yl, or morpholin-4-yl ring; n is 1, 2, 3, or 4; q is 0, 1, 2, or 3; R6 is C1-C6 alkyl, C3-C6 cycloalkyl substituted once with a phenyl, substituted phenyl, or CO2R1 group, aryl, aryl substituted from 1 to 3 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, N(R1)2, SO2N(R1)2, NH-Pg, C1-C6 alkoxy, benzyloxy, CO2R1, C5-C7 cycloalkyl, trifluoromethoxy, or nitro, tert-butoxy, (CH2)q-heterocycle, (CH2)q (heterocycle substituted 1 or 2 times independently with a C1-C6 alkyl, halo, benzyl, phenyl, or trifluoromethyl), (CH2)nS(O)rR1, C(CH3)2CH2N(R1)2, (CH2)nCHR8NHC(O)OC(CH3)3, (CH2)nCHR8NH2, (CH2)2NH-aryl, or NHR7; R6â€² is C1-C6 alkyl, C3-C6 cycloalkyl substituted once with a phenyl, substituted phenyl, or CO2R1 group, aryl, aryl substituted from 1 to 3 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, N(R1)2, SO2N(R1)2, NH-Pg, C1-C6 alkoxy, benzyloxy, CO2R1, C5-C7 cycloalkyl, trifluoromethoxy, or nitro, (CH2)q-heterocycle, (CH2)q (heterocycle substituted 1 or 2 times independently with a C1-C6 alkyl, halo, benzyl, phenyl, or trifluoromethyl), (CH2)nS(O)rR1, C(CH3)2CH2N(R1)2, (CH2)nCHR8NHâ€”C(O)OC(CH3)3, (CH2)nCHR8NH2, or (CH2)2NH-aryl; r is 0, 1, or 2; R7 is C1-C6 alkyl, phenyl, or phenyl substituted from 1 to 3 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, N(R1)2, SO2N(R1)2, NH-Pg, C1-C6 alkoxy, benzyloxy, CO2R1, C5-C7 cycloalkyl, trifluoromethoxy, or nitro; R8 is hydrogen or CO2R1; and R9, R10, and R11 are independently at each occurrence hydrogen, halo, CO2R1, aryl, aryl substituted from 1 to 3 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, N(R1)2, SO2N(R1)2, NH-Pg, C1-C6 alkoxy, benzyloxy, CO2R1, C5-C7 cycloalkyl, trifluoromethoxy, or nitro, thiophene, C1-C4 alkoxy, (C1-C3 alkyl)-phenyl, or C2-C6 alkenyl; R12 is C1-C6 alkyl, (C1-C4 alkyl)-phenyl, aryl, aryl substituted from 1 to 3 times independently with C1-C6 alkyl, C1-C4 alkoxy, halo, hydroxy, trifluoromethyl, N(R1)2, SO2N(R1)2, NH-Pg, C1-C6 alkoxy, benzyloxy, CO2R1, C5-C7 cycloalkyl, trifluoromethoxy, or nitro, heterocycle or heterocycle substituted 1 or 2 times independently with a C1-C6 alkyl, halo, benzyl, phenyl, or trifluoromethyl; or a pharmaceutical salt thereof; provided that if R9 and R10 are hydrogen and R11 is chloro, then het is not