Patent ID: 6632819
Filing Date: 2003-10-14
Classification: A61K,C07D

Abstract:
A pharmaceutical composition useful for treating infection by HIV which comprises an antiviral effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and an antiviral effective amount of one or more AIDS treatment agents selected from the group consisting of:(a) an AIDS antiviral agent; (b) an anti-infective agent; (c) an immunomodulator; and (d) HIV entry inhibitors; said compound of formula I has the structure â€ƒwherein: R1, R2, R3, R4 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, C2-C6 alkynyl, halogen, CN, phenyl, nitro, OC(O)R15, C(O)R15, C(O)OR16, C(O)NR17R18, OR19, SR20 and NR21R22; R15, is independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl and C4-C6 cycloalkenyl; R16, R19, and R20 are each independently selected from the group consisting of H, C1-C6 alkyl, C1-6 alkyl substituted with one to three halogen atoms, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the oxygen or sulfur to which R16, R19, or R20 is attached; R17 and R18 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl, C4-C6 cycloalkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon double bond of said C3-C6 alkenyl or the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the nitrogen to which R17 and R18 is attached; R21 and R22 are each independently selected from the group consisting of H, OH, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl, C5-C6 cycloalkenyl, C3-C6 alkynyl, and C(O)R23; provided the carbon atoms which comprise the carbon-carbon double bond of said C3-C6 alkenyl, C4-C6 cycloalkenyl, or the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the nitrogen to which R21 and R22 is attached; R23 is selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, and C2-C6 alkynyl; R5 is (O)m, wherein m is 0 or 1; n is 1 or 2; R6 is selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C4-C6 cycloalkenyl, C(O)R24, C(O)OR25, C(O)NR26R27, C3-C6 alkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon double bond of said C3-C6 alkenyl or the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the nitrogen to which R6 is attached; R24 is selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl, C4-C6 cycloalkenyl, and C3-C6 alkynyl; R25 is selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the oxygen to which R25 is attached; R26 and R27 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl, C5-C6 cycloalkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon double bond of said C3-C6 alkenyl, C5-C6 cycloalkenyl, or the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the nitrogen to which R26 and R27 are attached; R7, R8, R9, R10, R11, R12, R13, and R14 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, C2-C6 alkynyl, CR28R29OR30, C(O)R31, CR32(OR33)OR34, CR35NR36R37, C(O)OR38, C(O)NR39R40, CR41R42F, CR43F2 and CF3; R28, R29, R30, R31, R32, R35, R41, R42 and R43 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, C2-C6 alkynyl and C(O)R44; R33, R34 and R38 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl, C4-C6 cycloalkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the oxygen to which R34 and R38 are attached; R36 and R37 are each independently selected from the group consisting of H, C1-C6 alkyl, C1-C6 cycloalkyl, C3-C6 alkenyl, C4-C6 cycloalkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the nitrogen to which R36 and R37 are attached; R39 and R40 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the nitrogen to which R39 and R40 are attached; R44 is selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, and C2-C6 alkynyl; Ar is selected from the group consisting of A1, A2, A3, A4, A5, B1, B2, B3, B4, C1, C2, C3, D1, D2, and D3 are each independently selected from the group consisting of H, CN, halogen, NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, C2-C6 alkynyl, OR45, NR46R47, SR48, N3 and CH(â€”N&boxH;Nâ€”)â€”CF3; R45 is selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl and C3-C6 alkynyl; provided the carbon atoms which comprise the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the oxygen to which R45 is attached; R46 and R47 are each independently selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl, C5-C6 cycloalkenyl, C3-C6 alkynyl and C(O)R50; provided the carbon atoms which comprise the carbon-carbon double bond of said C5-C6 alkenyl, C4-C6 cycloalkenyl, or the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the nitrogen to which R46 and R47 are attached; R48 is selected from the group consisting of H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C4-C6 cycloalkenyl, C3-C6 alkynyl and C(O)R49; provided the carbon atoms which comprise the carbon-carbon triple bond of said C3-C6 alkynyl are not the point of attachment to the sulfur to which R48 is attached; R49 is C1-C6 alkyl or C3-C6 cycloalkyl; and R50 is selected from the group consisting of H, C1-C6 alkyl, and C3-C6 cycloalkyl.