Diphenyl substituted alkanes

A compound represented by structural Formula I:

• or a pharmaceutically acceptable salt thereof wherein:
• q is an integer selected from 0 (zero) and 1 (one);
• R1 is selected from the group consisting of:
• (a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 2 to 4 heteroatoms selected from N, S and O, wherein the heterocyclic ring is optionally substituted with R6,
• (b) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 2 heteroatoms selected from N and O, wherein the heterocyclic ring is optionally substituted with R6;
• (c) an 8-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-5 heteroatoms selected from one sulfur and 2-4 of nitrogen wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4-alkyl, —CN and 1-3 of fluoro, and
• (d) a 9-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-4 nitrogen atoms, wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro;
• (e) —C1-6alkyl, —C2-6alkenyl, and —C2-6alkynyl, said alkyl, alkenyl and alkynyl groups being optionally substituted with R12 and optionally substituted with R13;
• (f) —C3-6 cycloalkyl optionally substituted with 1-3 substituents selected from the group consisting of fluoro, —NH2, —OH and —C1-3alkyl optionally substituted with 1-3 of fluoro;
• (g) —O—R6a wherein R6a is selected from the group consisting of (1) —C1-6alkyl optionally substituted with R12 and optionally substituted with R13, (2) —C3-6 cycloalkyl optionally substituted with R12 and optionally substituted with R13 and (3) —C2-6alkyl-R10;
• with the proviso that when q is 0, R6a is not —C1-6alkyl substituted with Z1;
• and
• (h) —H, —OH, —CN, —CO2R4a, —C(O)NR7R8, —NR7R8, —NRbSOpRa, —NRbC(O)Ra, —NRbC(O)NRaRb, —S(O)pRa, and —S(O)pNRaRb;
• p is an integer selected from 0, 1 and 2;
• R2 is selected from the group consisting of (a) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —OH and fluoro, (b) —C3-6 cycloalkyl optionally substituted with 1-3 of fluoro, and
• n is an integer selected from 0, 1, 2 and 3;
• R3 is selected from the group consisting of —H, —F, —OH, and —C1-3alkyl optionally substituted with 1-5 fluoro;
• or
• R2 and R3 are taken in combination and represent a mono- or bi-cyclic ring system containing 3 to 8 carbon atoms, said system being optionally substituted with 1-2 groups selected from:
• C1-3alkyl, OC1-3alkyl, F, OH, mono-, di- or tri-fluoroC1-3alkyl and mono-, di- and tri-fluoroC1-3alkoxy;
• X is selected from the group consisting of —O—, —S— and —C(R14)2—;
• R4a is selected from the group consisting of —H, —C1-6alkyl and —C3-6 cycloalkyl;
• R4 is selected from the group consisting of —H, —C1-6alkyl and —C3-6 cycloalkyl;
• R5 is selected from the group consisting of —H, —F, and —CH3;
• R6 is selected from the group consisting of (a) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, —CN, —O—C1-4alkyl and fluoro, (b) —C1-6alkyl-R10, (c) —OC1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2 and fluoro, (d) —C3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —OH, —NH2, —CF3 and fluoro, (e) —NR7R8, (f) —SO2C1-3alkyl, (g) —CO2—R8, (h) —OH, (i) ═O (oxo), (j) —SH, (k) ═S, (l) —SMe, (m) —Cl, (n) —CF3, (o) —CN and (p) R10;
• R7 is selected from the group consisting of (a) —H, (b) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —F, —NH2 and —OH, (c) —C3-6 cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH, (d) —COC1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —F and —OH, (e) —COC3-6cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH, and (f) a 4-6 membered saturated heterocyclic ring containing one N, wherein the ring is bonded to the nitrogen in —NR7R8 through a carbon atom in the ring, and wherein the ring is optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH;
• R8 is selected from the group consisting of (a) —H, (b) —C1-6alkyl optionally substituted with one or more substituents selected from the group consisting of —F, —NH2 and —OH, and (c) —C3-6cycloalkyl optionally substituted with one or more substituents selected from the group consisting of methyl, —CF3, —F, —NH2 and —OH;
• R9 is selected from the group consisting of —H, —OH, —C1-3alkyl and —F;
• R10 is a heterocyclic ring selected from the group consisting of (a) azetidinyl optionally substituted with one or more of methyl, —F and —OH, (b) pyrrolidinyl optionally substituted with one or more of methyl, —F and —OH, (c) piperidinyl optionally substituted with one or more of methyl, —F and —OH and (d) morpholinyl optionally substituted with one or more of methyl, —F and —OH;
• and
• Y is selected from the group consisting of (a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from 1 to 4 of N and zero to 1 of S, wherein the heterocyclic ring is optionally substituted with R11, (b) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1 to 2 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11, (c) a 9-membered bicyclic aromatic or partially unsaturated heterocyclic ring containing 1 to 4 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11 and (d) a 10-membered bicyclic aromatic or partially unsaturated heterocyclic ring containing 1 to 4 N heteroatoms, wherein the heterocyclic ring is optionally substituted with R11;
• and
• R11 is selected from the group consisting of —F, —NH2, —OH, —OC3-4cycloalkyl, —C1-3alkyl optionally substituted with 1-3 fluoro, and —OC1-3alkyl optionally substituted with phenyl or 1-3 fluoro.
• R12 is selected from the group consisting of:
• —CO2R4a, —C(O)NR7R8, —N(Ra)2, —NRbSOpRa, —NRbC(O)Ra, —NRbC(O)NRaRb, —S(O)pNRaRb, —S(O)pRa, —F, —CF3, phenyl, Hetcy and Z1,
• R13 is selected from the group consisting of —OH, —NH2 and 1-5 of —F;
• R14 is selected from the group consisting of —H and —C1-4alkyl optionally substituted with 1-3 fluoro groups;
• each Ra is independently selected from the group consisting of
• a) —H,
• b) —C1-4alkyl, —C2-4alkenyl and —C2-4alkynyl, wherein each is optionally substituted with 1-2 substituents selected from the group consisting of:
• —OH, —OC1-4alkyl, —CN, —NH2, —NHC1-4alkyl, and —N(C1-4alkyl)2, and —CF3, and optionally with 1-3 of fluoro,
• c) Hetcy and Hetcy-C1-4alkyl-, the Hetcy moieties being optionally substituted on carbon with 1-2 substituents selected from the group consisting of —F, —OH, —CO2H, —C1-4alkyl, —CO2C1-4alkyl, —OC1-4alkyl, —NH2, —NHC1-4alkyl, —N(C1-4alkyl)2, —NHC(O)C1-4alkyl, oxo, —C(O)NH1-4alkyl and —C(O)N(C1-4alkyl)2;
• and optionally substituted on nitrogen when present with a group selected from —C1-4alkyl and —C1-4acyl;
• and the alkyl portion of Hetcy-C1-4alkyl- being optionally substituted with a member selected from the group consisting of —OH, —CN, —OC1-4alkyl, —NH2, —NHC1-4alkyl, —N(C1-4alkyl)2 and 1-3 of fluoro,
• d) Z2 and Z2—C1-4alkyl-, the alkyl portion of Z2—C1-4alkyl- being optionally substituted with a substituent selected from the group consisting of —OH, —CN, —OC1-4alkyl, —NH2, —NHC1-4alkyl, —N(C1-4alkyl)2 and 1-3 of fluoro;
• each Rb is independently selected from the group consisting of —H and —C1-3alkyl optionally substituted with 1-2 members selected from the group consisting of NH2, —OH, —F, —CN and —CF3;
• Rc, Rd, and Re are each independently selected from —H, —F, —Cl, —OH, —CN, —C1-4alkyl optionally substituted with 1-3 of fluoro, and —OC1-4alkyl optionally substituted with 1-3 of fluoro;
• Hetcy is selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetraydrofuranyl and β-lactamyl, δ-lactamyl, γ-lactamyl and tetrahydropyranyl;
• Z1 is selected from the group consisting of:
• a) Z2,
• b) an 8-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-5 heteroatoms selected from one sulfur and 2-4 of nitrogen wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4-alkyl, —CN and 1-3 of fluoro, and
• c) a 9-membered aromatic or partially unsaturated ortho-fused bicyclic ring system containing 3-4 nitrogen atoms, wherein one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro;
• and
• Z2 is selected from the group consisting of:
• a) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 2-4 nitrogen atoms, wherein one nitrogen in the ring is optionally substituted with a group selected from —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —CN and 1-3 of fluoro, and one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro,
• b) a 5-membered aromatic or partially unsaturated heterocyclic ring containing 2-3 heteroatoms selected from one oxygen or one sulfur and 1-2 of nitrogen, wherein one nitrogen in the ring is optionally substituted with a group selected from C1-4alkyl and C1-4alkyl substituted with a group selected from —NH2, —OH, —CN and 1-3 of fluoro, and one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, and C1-4alkyl optionally substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro, and
• c) a 6-membered aromatic or partially unsaturated heterocyclic ring containing 1-2 nitrogen atoms, wherein one nitrogen in the ring is optionally substituted with a group selected from —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —CN and 1-3 of fluoro, and one carbon in the ring is optionally substituted with a group selected from ═O, ═S, —SMe, —NH2, —CF3, —Cl, —C1-4alkyl and —C1-4alkyl substituted with a group selected from —NH2, —OH, —OC1-4alkyl, —CN and 1-3 of fluoro.