2,5-diarylpyrazines, 2,5-diarylpyridines and 2,5-diarylpyrimidines

A compound of Formula I

• 24
• or a pharmaceutically acceptable salt thereof, wherein:
• R is oxygen or absent;
• Z2 is nitrogen or CR2;
• Z3 is nitrogen or CR3;
• with the proviso that Z2 and Z3 are not both nitrogen;
• Ar1 and Ar2 are independently chosen from:
• phenyl which is mono-, di-, or tri-substituted with RA, and
• 1-naphthyl, 2-naphthyl, pyridyl, pyrimidinyl, pyrazinyl, pyridizinyl, thienyl, thiazolyl, pyrazolyl, imidazolyl, tetrazolyl, oxazolyl, isoxazolyl, pyrrolyl, furanyl, and triazolyl, each of which is optionally mono-, di-, or tri-substituted with RA;
• R1, R2, and R3 are independently selected from hydrogen, halogen, hydroxy, cyano, amino, nitro, C1-C6alkyl1, C1-C6alkyl1-O—, mono- or di-(C1-C6alkyl1)amino, C3-C7cycloalkyl2(C0-C4alkyl1), C3-C7cycloalkenyl2(C0-C4alkyll1), C3-C7cycloalkyl2(C0-C4alkyl1)-O—, C3-C7cycloalkenyl2(C0-C4alkyl1)-O—, haloC1-C6alkyl1, haloC1-C6akyl1-O—, and —S(O)n(C1-C6alkyl1),
• where each alkyl1 is independently straight or branched, contains 0 or 1 or more double or triple bonds, and is unsubstituted or substituted with one or more substituents independently chosen from halogen, hydroxy, oxo, cyano, C1-C4alkoxy, amino, and mono- or di-(C1-C4alkyl)amino, and
• where each C3-C7cycloalkyl2 and C3-C7cycloalkenyl2 is optionally substituted by one or more substituents independently chosen from halogen, hydroxy, oxo, cyano, C1-C4alkoxy, amino, and mono- or di-(C1-C4)alkylamino,
• with the proviso that not all of R1, R2, and R3 are hydrogen;
• RA is independently selected at each occurrence from halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, hydroxy, amino, C1-C6alkyl substituted with 0-2 RB, C2-C6alkenyl substituted with 0-2 RB, C2-C6alkynyl substituted with 0-2 RB, C3-C7cycloalkyl substituted with 0-2 RB, (C3-C7cycloalkyl)C1-C4alkyl substituted with 0-2 RB,
• C1-C6alkoxy substituted with 0-2 RB, —NH(C1-C6alkyl) substituted with 0-2 RB,
• —N(C1-C6alkyl)(C1-C6alkyl) where each C1-C6alkyl is independently substituted with 0-2 RB, —XRC, and Y;
• RB is independently selected at each occurrence from halogen, hydroxy, cyano, amino,
• C1-C4alkyl, C1-C4alkoxy, mono- or di-(C1-C4alkyl)amino,
• —S(O)n(alkyl), halo(C1-C4)alkyl, halo(C1-C4)alkoxy, —CO(C1-C4alkyl),
• —CONH(C1-C4alkyl), —CON(C1-C4alkyl)(C1-C4alkyl), —XRC, and Y;
• RC and RD, are the same or different, and are independently selected at each occurrence from:
• hydrogen, and
• straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, having 1 to 8 carbon atoms, and containing zero or one or more double or triple bonds, each of which 1 to 8 carbon atoms may be further substituted with one or more substituent(s) independently selected from oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, mono- or di-(C1-C4alkyl)amino, —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), and Z;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHRD—, —O—, —C(═O)—, —C(═O)O—, —S(O)n—, —NH—, —NRD—, —C(═O)NH—, —C(═O)NRD—, —S(O)nNH—,
• —S(O)nNRD—, —OC(═S)S—, —NHC(═O)—, —NRDC(═O)—, —NHS(O)n—, and —NRDS(O)n—;
• Y and Z are independently selected at each occurrence from:
• 3- to 7-membered carbocyclic or heterocyclic groups, which are saturated, partially unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, cyano, C1-C4alkyl, C1-C4alkoxy, mono- or di-(C1-C4alkyl)amino, and —S(O)n(alkyl), wherein said 3- to 7-memberered heterocyclic groups contain from 1 to 3 heteroatom(s) independently selected from N, O, and S, with remaining ring members being carbon;
• and
• n is independently selected at each occurrence from 0, 1, and 2.

13 A compound or salt according to claim 12, wherein:

• R1 and R3 are independently selected from hydrogen, cyano, amino, halogen, C1-C6alkyl, C1-C6alkoxy, (C3-C7cycloalkyl)C0-C3alkyl, (C3-C7cycloalkyl)C0-C3alkoxy, mono- or di-(C1-C6alkyl)amino, C1-C6haloalkyl, C1-C6haloalkoxy, and —SOn(C1-C6alkyl);
• RA is independently selected at each occurrence from
• i) halogen, cyano, nitro, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, hydroxy, amino, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, (C3-C7cycloalkyl)C1-C4alkyl, C1-C6alkoxy, mono- or di-(C1-C6alkyl)amino, —CHO, and —C(═O)CH3;
• ii) C1-C6alkoxy and C1-C6 alkyl which are unsubstituted or substituted with 1 or 2 groups independently selected from halogen, hydroxy, cyano, amino, oxo, C1-C4alkoxy,
• mono- or di-(C1-C6alkyl)amino, halo(C1-C4)alkyl, halo(C1-C4)alkoxy, C1-C4alkanoyl, morpholinyl, piperazinyl, piperidinyl, furanyl, and pyrrolidinyl, and
• iii) 3- to 7-membered carbocyclic or heterocyclic groups which are saturated, partially unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, cyano, C1-C4alkyl, C1-C4alkoxy, and mono- or di-(C1-C4alkyl)amino;
• and
• n is 0, 1, or 2.