Patent ID: 6486193
Filing Date: 2002-11-26
Classification: A61K,A61P,C07K

Abstract:
A compound of the formula whereine is an integer from 0 to 2; A is selected from the group consisting of â€”OH and â€”NRRâ€²; wherein R and Râ€² are independently selected from the group consisting of hydrogen and C1-C6 alkyl or R and Râ€² taken together with the nitrogen atom to which they are attached form a N-morpholino, N-piperidino, N-pyrrolidino, or N-isoindolyl; R1 is selected from the group consisting of hydrogen, C1-C6 alkyl, â€”(CH2)aâ€”CO2R5, â€”(CH2)aâ€”C(O)NH2, â€”(CH2)4NH2, â€”(CH2)3â€”NHâ€”C(NH)NH2, â€”(CH2)2â€”S(O)bâ€”CH3, â€”CH2â€”OH, â€”CH(OH)CH3, â€”CH2â€”SH, â€”(CH2)dâ€”Ar1, and â€”CH2â€”Ar2; wherein a is 1 or 2; b is 0, 1,or 2; d is an integer from 0 to 4; R5 is selected from the group consisting of hydrogen, C1-C4 alkyl, and benzyl; Ar1 is a radical selected from the group consisting of wherein R6 is from 1 to 2 substituents independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, hydroxy, and C1-C4 alkoxy; R7 is selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, and C1-C4 alkoxy; Ar2 is a radical selected from the group consisting of R2 is a radical selected from the group consisting of wherein wherein R2â€² is from 1 to 2 substituents selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, and C1-C4 alkoxy; R3 is selected from the group consisting of C1-C6 alkyl, â€”(CH2)mâ€”W, â€”(CH2)pâ€”Ar3, â€”(CH2)kâ€”CO2R9, â€”(CH2)mâ€”NR8â€²SO2â€”Y1, and â€”(CH2)mâ€”Zâ€”Q wherein m is an integer from 2 to 8; p is an integer from 0-10; k is an integer from 1 to 9; W is phthalimido; Ar3 is selected from the group consisting of wherein R23 is from 1 to 2 substituents independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, and C1-C4 alkoxy; R8â€² is hydrogen or C1-C6 alkyl; R9 is hydrogen or C1-C6 alkyl; Y1 is selected from the group consisting of hydrogen, â€”(CH2)jâ€”Ar4, and â€”N(R24)2 wherein j is 0 or 1; R24 each time selected is independently hydrogen or C1-C6 alkyl or are taken together with the nitrogen to which they are attached to form N-morpholino, N-piperidino, N-pyrrolidino, or N-isoindolyl; Ar4 is wherein R25 is from 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, and C1-C4 alkoxy; Z is selected from the group consisting of â€”Oâ€”, â€”NR8â€”, â€”C(O)NR8â€”, â€”NR8C(O)â€”, â€”NR8C(O)NHâ€”, â€”NR8C(O)Oâ€”, and â€”OC(O)NHâ€”; wherein R8 is hydrogen or C1-C6 alkyl; Q is selected from the group consisting of hydrogen, â€”(CH2)nâ€”Y2, and â€”(CH2)xâ€”Y3; wherein n is an integer from 0 to 4; Y2 is selected from the group consisting of hydrogen, â€”(CH2)hâ€”Ar5 and â€”(CH2)tâ€”C(O)OR27 wherein Ar5 is selected from the group consisting of wherein R26 is from 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, and C1-C4 alkoxy; h is an integer from 0 to 6; t is an integer from 1 to 6; R27 is hydrogen or C1-C6 alkyl; x is an integer from 2 to 4; Y3 is selected from the group consisting of â€”N(R28)2, N-morpholino, N-piperidino, N-pyrrolidino, and N-isoindolyl; wherein R28 each time taken is independently selected from the group consisting of hydrogen and C1-C6 alkyl; R4 is selected from the group consisting of hydrogen, â€”C(O)R10, â€”C(O)â€”(CH2)qâ€”K and â€”Sâ€”G wherein R10 is selected from the group consisting of hydrogen, C1-C4 alkyl, phenyl, and benzyl; q is 0, 1, or 2; K is selected from the group consisting of wherein V is selected from the group consisting of a bond, â€”CH2â€”, â€”Oâ€”, â€”S(O)râ€”, â€”NR21â€”, and â€”NC(O)R22â€”; wherein r is 0, 1, or 2; R21 is selected from the group consisting of hydrogen, C1-C4 alkyl, and benzyl; R22 is selected from the group consisting of hydrogen, â€”CF3, C1-C10 alkyl, phenyl , and benzyl; R11 is selected from the group consisting of hydrogen, C1-C4 alkyl, and benzyl; R11â€² is selected from the group consisting of hydrogen, C1-C4 alkyl, and benzyl; G is selected from the group consisting of wherein w is an integer from 1 to 3; R12 is selected from the group consisting of hydrogen, C1-C6 alkyl, â€”CH2CH2S(O)fCH3, and benzyl; wherein f is 0, 1, or 2; R13 is selected from the group consisting of hydrogen, hydroxy, amino, C1-C6 alkyl, N-methylamino, N,N-dimethylamino, â€”CO2R17, and â€”OC(O)R18; wherein R17 is hydrogen, â€”CH2Oâ€”C(O)C(CH3)3, C1-C4 alkyl, benzyl, or diphenylmethyl; R18 is hydrogen, C1-C6 alkyl or phenyl; R14 is 1 or 2 substituents independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, or halogen; V1 is selected from the group consisting of â€”Oâ€”, â€”Sâ€”, and â€”NHâ€”; V2 is selected from the group consisting of â€”Nâ€” and â€”CHâ€”; V3 is selected from the group consisting of a bond and â€”C(O)â€”; V4 is selected from the group consisting of â€”Oâ€”, â€”Sâ€”, â€”NR19â€”, and â€”NC(O)R20â€”; wherein R19 is hydrogen, C1-C4 alkyl, or benzyl; R20 is hydrogen, â€”CF3, C1-C10 alkyl, or benzyl; R15 is selected from the group consisting of hydrogen, C1-C6 alkyl and benzyl; R16 is selected from the group consisting of hydrogen and C1-C4 alkyl; and stereoisomers, pharmaceutically acceptable salt, and hydrate thereof.