Patent ID: 6689765
Filing Date: 2004-02-10
Classification: A61K,A61P,C07D

Abstract:
A method of treating Human Immunodeficiency Virus comprising administering to a human in need of such treatment a CCR5 antagonist represented by the structural formula II: or a pharmaceutically acceptable salt thereof, wherein(1) R2 is R8a-phenyl, R8b-pyridyl R8b-thiophenyl or R8-naphthyl; R1 is hydrogen or C1-C6 alkyl; R2 is 6-membered heteroaryl substituted by R9, R10 and R11; 6-membered heteroaryl N-oxide substituted by R9, R10 and R11; 5-membered heteroaryl substituted by R12 and R13; naphthyl; fluoronyl; diphenylmethyl; R3 is hydrogen, C1-C6 alkyl, (C1-C6)alkoxy(C1-C6)alkyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl(C1-C6 )alkyl, R8-phenyl, R8-phenyl(C1-C6 )alkyl, R8-naphthyl, R8-naphthyl(C1-C6)alkyl, R8-heteroaryl or R8-heteroaryl(C1-C6)alkyl; R4, R5, R7 and R13 are independently selected from the group consisting of hydrogen and (C1-C6)-alkyl; R6 is hydrogen, C1-C6 alkyl or C2-C6 alkenyl; R8 is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen C1-C6 alkyl, C1-C6 alkoxy, â€”CF3, CF3Oâ€”, CH3C(O)â€”, â€”CN, CH3SO2â€”, CF3SO2â€”, R14-phenyl, R14-benzyl, CH3C(&boxH;NOCH3), CH3C(&boxH;NOCH2CH3) â€”NH2, â€”NHCOCF3, â€”NHCONH(C1-C6 alkyl), â€”NHCO(C1-C6 alkyl), â€”NHSO2(C1-C6 alkyl), 5-membered heteroaryl and wherein X is â€”Oâ€”, â€”NHâ€” or â€”N(CH3);R8a is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, â€”CF3, CF3Oâ€”, â€”CN, CF3SO2â€”, R14-phenyl, â€”NHCOCF3, 5-membered heteroaryl and wherein X is as defined above;R8b is 1 to 3 substituents independently selected from the group consisting of hydrogen, halogen, â€”CF3, CF3Oâ€”, CH3C(O)â€”, â€”CN, CF3SO2â€”, R14-benzyl, CH3C(&boxH;NOCH3), CH3C(&boxH;NOCH2CH3), â€”NHCOCF3, 5-membered heteroaryl and wherein X is as defined above;R8 and R10 are independently selected from the group consisting of (C1-C6)alkyl, halogen, â€”NR17R18, â€”OH, â€”CF3, â€”OCH3, â€”O-acyl, â€”OCF3 and â€”Si(CH3)3; R11 is R9, hydrogen, phenyl, â€”NO2, â€”CN, â€”CH2F, â€”CHF2, â€”CHO, â€”CH&boxH;NOR17, pyridyl, pyridyl N-oxide, pyrimidinyl, pyrazinyl, â€”N(R17)CONR18R19, â€”NHCONH(chloro-(C1-C6)alkyl), â€”NHCONH((C3-C1)cycloalkyl(C1-C6)alkyl), â€”NHCO(C1-C6)alkyl, â€”NHCOCF3, â€”NHSO2N((C1-C6)alkyl)2, â€”NHSO2(C1-C6)alkyl, â€”N(SO2CF3)2, â€”NHCO2(C1-C6)alkyl, C3-C10 cycloalkyl, â€”SR20, â€”SOR20, â€”SO2R20, â€”SO2NH(C1-C6)alkyl, â€”OSO2(C1-C6)alkyl, â€”OSO2CF3, hydroxy(C1-C6)alkyl, â€”CON R17R18, â€”CON(CH2CH2â€”Oâ€”CH3)2, â€”OCONH(C1-C6)alkyl, â€”CO2R17, â€”Si(CH3)3 or â€”B(OC(CH3)2)2; R12 is (C1-C6)alkyl, â€”NH2 or R14-phenyl; R14 is 1 to 3 substituents independently selected from the group consisting of hydrogen, (C1-C6) alkyl, â€”CF3, â€”CO2R17, â€”CN, (C1-C6)alkoxy and halogen; R15 and R16 are independently selected from the group consisting of hydrogen and C1-C6 alkyl, or R15 and R16 together are a C2-C5 alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R17, R18 and R19 are independently selected from the group consisting of H and C1-C6 alkyl; and R20 is C1-C6 alkyl or phenyl; or (2) Ra is R8-phenyl, R8-pyridyl or R8-thiophenyl; R2 is fluorenyl, diphenylmethyl, and R1, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 are as defined in (1); in combination with one or more antiviral agents selected from the group consisting of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, hydroxyurea, ribavirin, IL-2IL-12, pentafuside and Yissum No. 11607.