4-cyanophenylamino-substituted bicyclic heterocyclic compounds as hiv inhibitors

A compound of formula IB:

• where the dashed line represents a double bond that may be located either between A and C(V) or between C(V) and D,
• A is S or C(Z);
• D is S or C(W);
• provided that one and only one of A or D is S;
• W and Z are, independently, H, F, Cl, Br, C1-C6 alkyl, C2-C6 alkenyl, OC1-C6 alkyl, C3-C6 cycloalkyl, OC3-C6 cycloalkyl, phenyl or benzyl;
• wherein the alkyl, alkenyl, cycloalkyl, phenyl groups and the phenyl moiety of the benzyl group are optionally substituted with 1-3 groups selected from halogen, CF3, C1-C3 alkyl, or OC1-C3 alkyl;
• V is H, halogen or C1-C6 alkyl;
• or V and W, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• or V and Z, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• Ar is selected from (a), (b), (c), or (d) below:
• wherein each R1 is selected from methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, C3-C6 cycloalkyl, cyano, CH═CHCN, Cl, Br, I, acetyl, or C1-C6 alkyl-NH;
• R4, R5, and each R6 are independently selected from H, F, Cl, Br, CH3, CF3, CH2F, CHF2, isopropyl, cyclopropyl, OCH3, OH, OCF3, NH2, or NHCH3;
• or R6 and RP on adjacent ring atoms, together with the ring atoms to which they are attached, form an additional fused five-membered ring;
• Q and Q′ are independently selected from N or CH;
• R7 is Cl, Br, I, CH3, CF3, OCH3, isopropyl, cyclopropyl, t-butyl, or cyclobutyl;
• and
• R8-R11 are, independently, H or CH3;
• or a pharmaceutically acceptable salt, solvate, hydrate or polymorph thereof.

A pharmaceutical composition comprising a compound of Formula I:

• where the dashed line represents a double bond that may be located either between A and C(V) or between C(V) and D,
• A is S or C(Z);
• D is S or C(W);
• provided that one and only one of A or D is S;
• T is NH, O, or S;
• W and Z are, independently, H, F, Cl, Br, C1-C6 alkyl, C2-C6 alkenyl, OC1-C6 alkyl, C3-C6 cycloalkyl, OC3-C6 cycloalkyl, phenyl or benzyl;
• wherein the alkyl, alkenyl, cycloalkyl, phenyl groups and the phenyl moiety of the benzyl group are optionally substituted with 1-3 groups selected from halogen, CF3, C1-C3 alkyl, or OC1-C3 alkyl;
• V is H, halogen, C1-C6 alkyl;
• or V and W, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• or V and Z, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• Ar is selected from (a), (b), (c), or (d) below:
• wherein
• each Rp is selected from methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, C3-C6 cycloalkyl, cyano, CH═CHCN, Cl, Br, I, acetyl, or C1-C6 alkyl-NH;
• R4, R5, and each R6 are independently selected from H, F, Cl, Br, CH3, CF3, CH2F, CHF2, isopropyl, cyclopropyl, OCH3, OH, OCF3, NH2 or NHCH3;
• or R6 and RP on adjacent ring atoms, together with the ring atoms to which they are attached, form an additional fused five-membered ring;
• Q and Q′ are independently selected from N or CH;
• and
• R7 is Cl, Br, I, CH3, CF3, OCH3, isopropyl, cyclopropyl, t-butyl, or cyclobutyl;
• and R8-R11 are, independently, H or CH3;
• or a pharmaceutically acceptable salt, solvate, hydrate or polymorph thereof.

A method of inhibiting an immunodeficiency virus comprising contacting said immunodeficiency virus with a compound of Formula I, or pharmaceutically acceptable salt, solvate, hydrate or polymorph thereof:

• where the dashed line represents a double bond that may be located either between A and C(V) or between C(V) and D,
• A is S or C(Z);
• D is S or C(W);
• provided that one and only one of A or D is S;
• T is NH, O, or S;
• W and Z are, independently, H, F, Cl, Br, C1-C6 alkyl, C2-C6 alkenyl, OC1-C6 alkyl, C3-C6 cycloalkyl, OC3-C6 cycloalkyl, phenyl or benzyl;
• wherein the alkyl, alkenyl, cycloalkyl, phenyl groups and the phenyl moiety of the benzyl group are optionally substituted with 1-3 groups selected from halogen, CF3, C1-C3 alkyl, or OC1-C3 alkyl;
• V is H, halogen, C1-C6 alkyl;
• or V and W, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• or V and Z, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• Ar is selected from (a), (b), (c), or (d) below:
• wherein
• each R1 is selected from methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, C3-C6 cycloalkyl, cyano, CH═CHCN, Cl, Br, I, acetyl, or C1-C6 alkyl-NH;
• R4, R5, and each R6 are independently selected from H, F, Cl, Br, CH3, CF3, CH2F, CHF2, isopropyl, cyclopropyl, OCH3, OH, OCF3, NH2 or NHCH3;
• or R6 and RP on adjacent ring atoms, together with the ring atoms to which they are attached, form an additional fused five-membered ring;
• Q and Q′ are independently selected from N or CH;
• R7 is Cl, Br, I, CH3, CF3, OCH3, isopropyl, cyclopropyl, t-butyl, or cyclobutyl;
• and
• R8-R11 are, independently, H or CH3.

A method for preventing infection with an immunodeficiency virus in a subject, treating infection with an immunodeficiency virus in a subject, preventing acquired immunodeficiency syndrome (AIDS) in a subject, treating acquired immunodeficiency syndrome (AIDS) in a subject, preventing an AIDS-related complex (ARC) in a subject or treating an AIDS-related complex (ARC) in a subject, comprising administering to the subject a pharmaceutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt, solvate, hydrate or polymorph thereof:

• where the dashed line represents a double bond that may be located either between A and C(V) or between C(V) and D,
• A is S or C(Z);
• D is S or C(W);
• provided that one and only one of A or D is S;
• T is NH, O, or S;
• W and Z are, independently, H, F, Cl, Br, C1-C6 alkyl, C2-C6 alkenyl, OC1-C6 alkyl, C3-C6 cycloalkyl, OC3-C6 cycloalkyl, phenyl or benzyl;
• wherein the alkyl, alkenyl, cycloalkyl, phenyl groups and the phenyl moiety of the benzyl group are optionally substituted with 1-3 groups selected from halogen, CF3, C1-C3 alkyl, or OC1-C3 alkyl;
• V is H, halogen, C1-C6 alkyl;
• or V and W, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• or V and Z, together with the ring atoms to which they are attached, form an additional, fused 5-, 6-, or 7-membered ring, optionally containing one or two heteroatoms, said additional ring may be saturated, unsaturated, or aromatic;
• Ar is selected from (a), (b), (c), or (d) below:
• wherein
• each Rp is selected from methyl, ethyl, propyl, isopropyl, cyclopropylmethyl, C3-C6 cycloalkyl, cyano, CH═CHCN, Cl, Br, I, acetyl, or C1-C6 alkyl-NH;
• R4, R5, and each R6 are independently selected from H, F, Cl, Br, CH3, CF3, CH2F, CHF2, isopropyl, cyclopropyl, OCH3, OH, OCF3, NH2 or NHCH3;
• or R6 and RP on adjacent ring atoms, together with the ring atoms to which they are attached, form an additional fused five-membered ring;
• Q and Q′ are independently selected from N or CH;
• R7 is Cl, Br, I, CH3, CF3, OCH3, isopropyl, cyclopropyl, t-butyl, or cyclobutyl;
• and
• R8-R11 are, independently, H or CH3.