Capsaicin receptor ligands

A compound of the formula:

• 207
• or a pharmaceutically acceptable salt thereof, wherein:
• A is absent or is selected from the group consisting of O, S, NRA, CRBRB′, NRACRBRB′, CRBRB′NRA, —CRA═CRB—, and C3H4;
• where RA, RB, and RB′ are independently selected at each occurrence from hydrogen or alkyl;
• Z is oxygen or sulfur;
• R3 and R4 are independently selected at each occurrence from the group consisting of hydrogen;
• halogen;
• hydroxy;
• amino;
• cyano;
• nitro;
• —COOH;
• —CHO, optionally substituted alkyl;
• optionally substituted alkenyl;
• optionally substituted alkynyl;
• optionally substituted alkoxy;
• optionally substituted mono or dialkylamino;
• optionally substituted alkylthio;
• optionally substituted alkyl ketone;
• optionally substituted alkylester;
• optionally substituted alkylsulfinyl;
• optionally substituted alkylsulfonyl;
• optionally substituted mono- or di-alkylcarboxamide;
• optionally substituted —S(O)nNHalkyl;
• optionally substituted —S(O)nN(alkyl)(alkyl);
• optionally substituted —NHC(═O) alkyl;
• optionally substituted —NC(═O)(alkyl)(alkyl);
• optionally substituted —NHS(O)nalkyl;
• optionally substituted —NS(O)n(alkyl)(alkyl);
• optionally substituted saturated or partially unsaturated heterocycloalkyl of from 5 to 8 atoms, which saturated or partially unsaturated heterocycloalkyl contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• optionally substituted aryl having from 1 to 3 rings;
• and optionally substituted heteroaryl, said heteroaryl having from 1 to 3 rings, 5 to 8 ring members in each ring and, in at least one of said rings, from 1 to about 3 heteroatoms per ring selected from the group consisting of N, O, and S;
• or any two
• R3 and R4 not attached to the same carbon may be joined to form an optionally substituted aryl ring, a saturated or partially unsaturated carbocyclic ring of from 5 to 8 members, which carbocyclic ring is optionally substituted, or a saturated, partially unsaturated, or aromatic heterocyclic ring of from 5 to 8 members, which heterocyclic ring is optionally substituted and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• Ar1 and Ar2 may be the same or different and are selected from the group consisting of cyclohexyl, cyclopentyl, piperidinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, pyrazinyl, benzimidazolyl, naphthyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzo[b]thiophenyl, benz[d]isoxazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, and quinoxalinyl, each of which is optionally mono-, di-, or trisubstituted with R5;
• or
• Ar1 and Ar2 may be the same or different and represent a bicyclic oxygen-containing group of the formula:
• 208
• optionally mono-, di-, or trisubstituted with R5, where L represents point of attachment and may be at any point on the benzene ring, and the oxygen-containing ring of the bicyclic oxygen-containing group consists of from 5 to 8 ring atoms, contains 1 or 2 oxygen atoms and remaining ring atoms are carbon;
• R5 is independently selected at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R6 is independently selected at each occurrence from the group consisting of halogen, hydroxy, cyano, C1-4alkyl, C1-4alkoxy, —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —S(O)n(C1-4alkyl) halo(C1-4)alkyl, halo(C1-4)alkoxy, CO(C1-4alkyl), CONH(C1-4alkyl), CON(C1-4alkyl1)(C1-4alkyl2) where alkyl1 and alkyl2 may be joined to form a heterocycloalkyl ring of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, —XR7, and Y;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHR8—, —O—, —S(O)n—, —NH—, —NR8—, —C(═O)—, —C(═O)O—, —C(═O)NH—, —C(═O)NR8—, —S(O)nNH—, —S(O)nNR8—, NHC(═O)—, —NR8C(═O)—, —NHS(O)n—, and —NR8S(O)n—;
• R7 and R8 are independently selected at each occurrence from hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 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, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(alkyl), —NH(alkyl), —N(alkyl)(alkyl), —NHC(O)(alkyl), —N(alkyl)C(O)(alkyl), —NHS(O)n(alkyl), —S(O)n(alkyl), —S(O)nNH(alkyl), —S(O)nN(alkyl3)(alkyl4) where alkyl3 and alkyl4 may be joined to form a heterocycloalkyl ring consisting of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, and Y′;
• Y and Y′ are independently selected at each occurrence from 3- to 8-membered carbocyclic or heterocyclic groups which are saturated, unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, mono- or dialkylamino, and alkylthio;
• wherein said 3- to 8-memberered heterocyclic groups contain one or more heteroatom(s) independently selected from N, O, and S;
• n is independently chosen at each occurrence from 0, 1, and 2;
• and
• x is 1 or 3.

A compound of the formula:

• 211
• or a pharmaceutically acceptable salt thereof, wherein:
• A is absent or is selected from the group consisting of O, S, NRA, CRBRB′, NRACRBRB′, CRBRB′NRA, —CRA═CRB—, and C3H4;
• where RA, RB, and RB′ are independently selected at each occurrence from hydrogen or alkyl;
• R3 and R4 are independently selected at each occurrence from the group consisting of hydrogen;
• halogen;
• hydroxy;
• amino;
• cyano;
• nitro;
• —COOH;
• —CHO, optionally substituted alkyl;
• optionally substituted alkenyl;
• optionally substituted alkynyl;
• optionally substituted alkoxy;
• optionally substituted mono or dialkylamino;
• optionally substituted alkylthio;
• optionally substituted alkyl ketone;
• optionally substituted alkylester;
• optionally substituted alkylsulfinyl;
• optionally substituted alkylsulfonyl;
• optionally substituted mono- or di-alkylcarboxamide;
• optionally substituted —S(O)nNHalkyl;
• optionally substituted —S(O)nN (alkyl)(alkyl);
• optionally substituted —NHC(═O) alkyl;
• optionally substituted —NC(═O)(alkyl)(alkyl);
• optionally substituted —NHS(O)nalkyl;
• optionally substituted —NS(O)n(alkyl)(alkyl);
• optionally substituted saturated or partially unsaturated heterocycloalkyl of from 5 to 8 atoms, which saturated or partially unsaturated heterocycloalkyl contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• optionally substituted aryl having from 1 to 3 rings;
• and optionally substituted heteroaryl, said heteroaryl having from 1 to 3 rings, 5 to 8 ring members in each ring and, in at least one of said rings, from 1 to about 3 heteroatoms per ring selected from the group consisting of N, O, and S;
• or any two
• R3 and R4 not attached to the same carbon may be joined to form an optionally substituted aryl ring;
• a saturated or partially unsaturated carbocyclic ring of from 5 to 8 members, which carbocyclic ring is optionally substituted;
• or a saturated, partially unsaturated, or aromatic heterocyclic ring of from 5 to 8 members, which heterocyclic ring is optionally substituted and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• Ar1 and Ar2 may be the same or different and are selected from the group consisting of cyclohexyl, cyclopentyl, piperidinyl, piperazinyl, pyrrolyl, furanyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, pyrazinyl, benzimidazolyl, naphthyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzo[b]thiophenyl, benz[d]isoxazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, and quinoxalinyl;
• wherein Ar1 is optionally mono-, di-, or trisubstituted with R5, and Ar2 is optionally mono-, di-, or trisubstituted with R9;
• or
• Ar1 and Ar2 may be the same or different and represent a bicyclic oxygen-containing group of the formula:
• 212
• optionally mono-, di-, or trisubstituted with R5, where L represents point of attachment and may be at any point on the benzene ring, and the oxygen-containing ring of the bicyclic oxygen-containing group consists of from 5 to 8 ring atoms, contains 1 or 2 oxygen atoms and remaining ring atoms are carbon;
• R5 is independently selected at each occurrence from the group consisting of cyano, nitro, haloalkyl, haloalkoxy, hydroxy, amino, alkyl substituted with 0-2 R6, alkenyl substituted with 0-2 R6, alkynyl substituted with 0-2 R6, alkoxy substituted with 0-2 R6, —NH(alkyl) substituted with 0-2 R6, —N(alkyl)(alkyl) where each alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R9 is independently selected at each occurrence from the group consisting of cyano, nitro, haloalkoxy, hydroxy, amino, alkyl substituted with 0-2 R6, alkenyl substituted with 0-2 R6, alkynyl substituted with 0-2 R6, alkoxy substituted with 0-2 R6, —NH(alkyl) substituted with 0-2 R6, —N(alkyl)(alkyl) where each alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R6 is independently selected at each occurrence from the group consisting of halogen, hydroxy, cyano, alkyl, alkoxy, —NH(alkyl), —N(alkyl)(alkyl), —S(O)n(alkyl), haloalkyl, haloalkoxy, CO(alkyl), CONH(alkyl), CON(alkyl1)-(alkyl2) where alkyl1 and alkyl2 may be joined to form a heterocycloalkyl ring of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, —XR7, and Y;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHR8—, —O—, —S(O)n—, —NH—, —NR8—, —C(═O)—, —C(═O)O—, —C(═O)NH—, —C(═O)NR8—, —S(O)nNH—, —S(O)nNR8—, NHC(═O)—, —NR8C(═O)—, —NHS(O)n—, and —NR8S(O)n—;
• R7 and R8 are independently selected at each occurrence from hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 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, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(alkyl), —NH(alkyl), —N(alkyl)(alkyl), —NHC(O)(alkyl), —N(alkyl)C(O)(alkyl), —NHS(O)n(alkyl), —S(O)n(alkyl), —S(O)nNH(alkyl), —S(O)nN(alkyl3)(alkyl4) where alkyl3 and alkyl4 may be joined to form a heterocycloalkyl ring consisting of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, and Y′;
• Y and Y′ are independently selected at each occurrence from 3- to 8-membered carbocyclic or heterocyclic groups which are saturated, unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, mono- or dialkylamino, and alkylthio;
• wherein said 3- to 8-memberered heterocyclic groups contain one or more heteroatom(s) independently selected from N, O, and S;
• and
• n is independently chosen at each occurrence from 0, 1, and 2.

A compound of the formula:

• 213
• or a pharmaceutically acceptable salt thereof, wherein:
• G, Q, T, and W are the same or different and are selected from the group consisting of N, CH, and CR5, wherein T or W or both is N;
• A is absent or is selected from the group consisting of O, S, NRA, CRBRB′, NRACRBRB′, CRBRB′NRA, —CRA═CRB—, and C3H4;
• where RA, RB, and RB′ are independently selected at each occurrence from hydrogen or alkyl;
• Z is oxygen or sulfur;
• R3 and R4 are independently selected at each occurrence from the group consisting of hydrogen;
• halogen;
• hydroxy;
• amino;
• cyano;
• nitro;
• —COOH;
• —CHO, optionally substituted C1-6alkyl;
• optionally substituted C2-6alkenyl;
• optionally substituted C2-6alkynyl;
• optionally substituted C1-6alkoxy;
• optionally substituted mono or di(C1-6)alkylamino;
• optionally substituted C1-6alkylthio;
• optionally substituted C1-6alkyl ketone;
• optionally substituted C1-6alkylester;
• optionally substituted C1-6alkylsulfinyl;
• optionally substituted C1-6alkylsulfonyl;
• optionally substituted mono- or di(C1-6)alkylcarboxamide;
• optionally substituted —S(O)nNH C1-6alkyl;
• optionally substituted —S(O)nN(C1-6alkyl)(C1-6alkyl);
• optionally substituted —NHC(═O) C1-6alkyl;
• optionally substituted —NC(═O)(C1-6alkyl)(C1-6alkyl);
• optionally substituted —NHS(O)nC1-6alkyl;
• optionally substituted —NS(O)n(C1-6alkyl)(C1-6alkyl);
• optionally substituted saturated or partially unsaturated heterocycloalkyl of from 5 to 8 atoms, which saturated or partially unsaturated heterocycloalkyl contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• optionally substituted aryl having from 1 to 3 rings;
• and optionally substituted heteroaryl, said heteroaryl having from 1 to 3 rings, 5 to 8 ring members in each ring and, in at least one of said rings, from 1 to about 3 heteroatoms per ring selected from the group consisting of N, O, and S;
• or any two
• R3 and R4 not attached to the same carbon may be joined to form an optionally substituted aryl ring;
• a saturated or partially unsaturated carbocyclic ring of from 5 to 8 members, which carbocyclic ring is optionally substituted;
• or a saturated, partially unsaturated, or aromatic heterocyclic ring of from 5 to 8 members, which heterocyclic ring is optionally substituted and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• R5 represents 1 to 3 substituents and is independently selected at each occurrence from the group consisting of cyano, hydroxy, amino, C3-6 alkyl substituted with 0-2 R6, C2-6 alkenyl substituted with 0-2 R6, C2-6 alkynyl substituted with 0-2 R6, C3-6 alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R9 represents 0 to 3 substituents and is independently selected at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R6 is independently selected at each occurrence from the group consisting of halogen, hydroxy, cyano, C1-4alkyl, C1-4alkoxy, —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —S(O)n(C1-4alkyl), halo(C1-4)alkyl, halo(C1-4)alkoxy, CO(C1-4alkyl), CONH(C1-4alkyl), CON(C1-4alkyl1)(C1-4alkyl2) where alkyl1 and alkyl2 may be joined to form a heterocycloalkyl ring of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, —XR7, and Y;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHR8—, —O—, —S(O)n—, —NH—, —NR8—, —C(═O)—, —C(═O)O—, —C(═O)NH—, —C(═O)NR8—, —S(O)nNH—, —S(O)nNR8—, NHC(═O)—, —NR8C(═O)—, —NHS(O)n—, and —NR8S(O)n—;
• R7 and R8 are independently selected at each occurrence from hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 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, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(C1-4alkyl), —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —NHC(O)(C1-4alkyl), —N(C1-4alkyl) C(O)(C1-4alkyl), —NHS(O)n(C1-4alkyl), —S(O)n(C1-4alkyl), —S(O)nNH(C1-4alkyl), —S(O)nN(C1-4alkyl3)(C1-4alkyl4) where C1-4alkyl3 and C1-4alkyl4 may be joined to form a heterocycloalkyl ring consisting of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, and Y′;
• Y and Y′ are independently selected at each occurrence from 3- to 8-membered carbocyclic or heterocyclic groups which are saturated, unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, mono- or di(C1-4)alkylamino, and C1-4alkylthio;
• wherein said 3- to 8-memberered heterocyclic groups contain one or more heteroatom(s) independently selected from N, O, and S;
• and
• n is independently chosen at each occurrence from 0, 1, and 2.

A compound of the formula:

• 214
• or a pharmaceutically acceptable salt thereof, wherein:
• A is selected from the group consisting of NH, —CH═CH—, and CH2NH;
• R4 is independently chosen from hydrogen and C1-4 alkyl;
• R5 represents 0 to 2 substituents and is independently chosen at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6,
• —N(C1-6alkyl)(C1-6alkyl) where each C1-6 alkyl is independently substituted with 0-2 R6;
• R9 represents 0 to 2 substituents and is independently chosen at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, and —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6;
• R5A is independently selected from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6 alkyl, C1-6 alkoxy, —NH(C1-6 alkyl), and —N(C1-6 alkyl)(C1-6 alkyl);
• R9B is independently selected from the group consisting of halogen, nitro, halo(C1-6)alkoxy, hydroxy, amino, C1-6 alkyl, C1-6 alkoxy, —NH(C1-6 alkyl), and —N(C1-6 alkyl)(C1-6 alkyl) and
• R6 is independently selected at each occurrence the group consisting of halogen, hydroxy, C1-4alkyl, C1-4alkoxy, —NH(C1-4 alkyl), and —N(C1-4 alkyl)(C1-4 alkyl).

A compound of the formula:

• 215
• or a pharmaceutically acceptable salt thereof, wherein:
• A is selected from the group consisting of a single bond, S, NRA, CHRB, NRACHRB, CHRBNRA, —CRA═CRB—, and C3H4;
• where RA and RB are independently selected at each occurrence from the group consisting of hydrogen and alkyl;
• R3 and R4 are independently selected at each occurrence from the group consisting of hydrogen;
• halogen;
• hydroxy;
• amino;
• cyano;
• nitro;
• —COOH;
• —CHO, optionally substituted alkyl;
• optionally substituted alkenyl;
• optionally substituted alkynyl;
• optionally substituted alkoxy;
• optionally substituted mono or dialkylamino;
• optionally substituted alkylthio;
• optionally substituted alkyl ketone;
• optionally substituted alkylester;
• optionally substituted alkylsulfinyl;
• optionally substituted alkylsulfonyl;
• optionally substituted mono- or di-alkylcarboxamide;
• optionally substituted —S(O)nNHalkyl;
• optionally substituted —S(O)nN (alkyl)(alkyl);
• optionally substituted —NHC(═O) alkyl;
• optionally substituted —NC(═O)(alkyl)(alkyl);
• optionally substituted —NHS(O)nalkyl;
• optionally substituted NS(O)n(alkyl) (alkyl);
• optionally substituted saturated or partially unsaturated heterocycloalkyl of from 5 to 8 atoms, which saturated or partially unsaturated heterocycloalkyl contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• optionally substituted aryl having from 1 to 3 rings;
• and optionally substituted heteroaryl, said heteroaryl having from 1 to 3 rings, 5 to 8 ring members in each ring and, in at least one of said rings, from 1 to about 3 heteroatoms per ring selected from the group consisting of N, O, and S;
• or any two
• R3 and R4 not attached to the same carbon may be joined to form an optionally substituted aryl ring;
• a saturated or partially unsaturated carbocyclic ring of from 5 to 8 members, which carbocyclic ring is optionally substituted;
• or a saturated, partially unsaturated, or aromatic heterocyclic ring of from 5 to 8 members, which heterocyclic ring is optionally substituted and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• R5 is independently selected at each occurrence from the group consisting of cyano, nitro, haloalkyl, haloalkoxy, C1-6 alkyl substituted with 0-2 R6, C2-6 alkenyl substituted with 0-2 R6, C2-6 alkynyl substituted with 0-2 R6, C1-6 alkoxy substituted with 0-2 R6, —NH(C1-6 alkyl) substituted with 0-2 R6, —N(C1-6 alkyl)(C1-6 alkyl) where each alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R9 represents 0-3 substituents and is independently selected at each occurrence from the group consisting of bromo, haloalkyl, haloalkoxy, hydroxy, C2-6 alkyl substituted with 0-2 R6, C2-6 alkenyl substituted with 0-2 R6, C2-6 alkynyl substituted with 0-2 R6, C2-6 alkoxy substituted with 0-2 R6, —NH(C2-6 alkyl) substituted with 0-2 R6, —N(C2-6 alkyl)(C2-6 alkyl) where each C2-6 alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R6 is independently selected at each occurrence from the group consisting of halogen, hydroxy, cyano, alkyl, alkoxy, —NH(alkyl), —N(alkyl)(alkyl), —S(O)n(alkyl), haloalkyl, haloalkoxy, CO(alkyl), CONH(alkyl), CON(alkyl1)(alkyl2) where alkyl1 and alkyl2 may be joined to form a heterocycloalkyl ring of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, —XR7, and Y;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHR8—, —O—, —S(O)n—, —NH—, —NR8—, —C(═O)—, —C(═O)O—, —C(═O)NH—, —C(═O)NR8—, —S(O)nNH—, —S(O)nNR8—, NHC(═O)—, —NR8C(═O)—, —NHS(O)n—, and —NR8S(O)n—;
• R7 and R8 are independently selected at each occurrence from straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 3 to 8 carbon atoms, and containing zero or one or more double or triple bonds, each of which 3 to 8 carbon atoms may be further substituted with one or more substituent(s) independently selected from oxo, hydroxy, halogen, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(alkyl),
• —NH(alkyl), —N(alkyl)(alkyl), —NHC(O)(alkyl), —N(alkyl)C(O)(alkyl), —NHS(O)n(alkyl),
• —S(O)n(alkyl), —S(O)nNH(alkyl), —S(O)nN(alkyl3)(alkyl4) where alkyl3 and alkyl4 may be joined to form a heterocycloalkyl ring consisting of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, and Y′;
• Y and Y′ are independently selected at each occurrence from 3- to 8-membered carbocyclic or heterocyclic groups which are saturated, unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, alkyl, alkoxy, haloalkyl, haloalkoxy, mono- or dialkylamino, and alkylthio;
• wherein said 3- to 8-memberered heterocyclic groups contain one or more heteroatom(s) independently selected from N, O, and S;
• and
• n is independently chosen at each occurrence from 0, 1, and 2.

A compound of the formula:

• 216
• or a pharmaceutically acceptable salt thereof, wherein:
• A is selected from the group consisting of NH, —CH═CH—, and CH2NH;
• R4 is independently selected at each occurrence from hydrogen and C1-4alkyl;
• R5 represents 0 to 2 substituents independently selected at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, and —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6;
• R9 represents 0 to 2 substituents and is independently selected at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, and —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6;
• R5A is independently selected from the group consisting of halogen, cyano, nitro, trifluoromethyl, trifluoromethoxy, hydroxy, amino, C1-6 alkyl, C1-6 alkoxy, —NH(C1-6 alkyl), and —N(C1-6 alkyl)(C1-C6 alkyl);
• R9B is independently selected from the group consisting of trifluoromethoxy, hydroxy, C2-6 alkyl, C2-6 alkoxy, —NH(C2-6 alkyl), and —N(C2-6 alkyl)(C2-6 alkyl);
• and
• R6 is independently selected at each occurrence from the group consisting of halogen, hydroxy, C1-4 alkyl, C1-4 alkoxy, —NH(C1-4 alkyl), and —N(C1-4 alkyl)(C1-4 alkyl).

A compound of the formula:

• 217
• or a pharmaceutically acceptable salt thereof, wherein the compound or pharmaceutically acceptable salt thereof exhibits an EC50 or Ki of 1 micromolar or less in a standard assay of capsaicin receptor mediated calcium mobilization;
• and wherein
• A is absent or is selected from the group consisting of O, S, NRA, CRBRB′, NRACRBRB′,
• CRBRB′NRA, —CRA=CRB—, and C3H4;
• where RA, RB, and RB′ are independently selected at each occurrence from hydrogen or C1-6 alkyl;
• Z is oxygen or sulfur;
• R1 and R2 independently represent hydrogen or C1-6 alkyl;
• or
• R1 and R2 are taken together to form a 5 to 8 membered nitrogen-containing ring of the formula:
• 218
• wherein x is 1, 2, or 3;
• R3 and R4 are independently chosen at each occurrence from the group consisting of hydrogen, halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6;
• C2-6alkynyl substituted with 0-2 R6;
• C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6,
• —XR7, and Y;
• or any two
• R3 and R4 not attached to the same carbon may be joined to form an aryl ring substituted with 0-3 R6, a saturated or partially unsaturated carbocyclic ring of from 5 to 8 members, which carbocyclic ring is substituted with 0-2 R6, or a saturated, partially unsaturated, or aromatic heterocyclic ring of from 5 to 8 members, which heterocyclic ring is substituted with 0-2 R6 and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• Ar1 and Ar2 may be the same or different and are selected from the group consisting of cyclohexyl, cyclopentyl, piperidinyl, piperazinyl, phenyl, pyrrolyl, furanyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, pyrazinyl, benzimidazolyl, naphthyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzo[b]thiophenyl, benz[d]isoxazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, and quinoxalinyl, each of which is optionally mono-, di-, or trisubstituted with R5;
• or
• Ar1 and Ar2 may be the same or different and represent a bicyclic oxygen-containing group of the formula:
• 219
• optionally mono-, di-, or trisubstituted with R5, where L represents point of attachment and may be at any point on the benzene ring, and the oxygen-containing ring of the bicyclic oxygen-containing group consists of from 5 to 8 ring atoms, contains 1 or 2 oxygen atoms and remaining ring atoms are carbon;
• R5 is independently selected at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6,
• —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R6 is independently selected at each occurrence from the group consisting of halogen, hydroxy, cyano, C1-4alkyl, C1-4alkoxy, —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —S(O)n(C1-4alkyl), halo(C1-4)alkyl, halo(C1-4)alkoxy, CO(C1-4alkyl), CONH(C1-4alkyl), CON(C1-4alkyl1)(C1-4alkyl2) where alkyl1 and alkyl2 may be joined to form a heterocycloalkyl ring of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, —XR7, and Y;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHR8—, —O—, —S(O)n—, —NH—, —NR8—, —C(═O)—, —C(═O)O—, —C(═O)NH—, —C(═O)NR8—, —S(O)NH—, —S(O)nNR8—, NHC(═O)—, —NR8C(═O)—, —NHS(O)n—, and —NR8S(O)n—;
• R7 and R8 are independently selected at each occurrence from hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 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, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(C1-4alkyl),
• —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —NHC(O)(C1-4alkyl) —N(C1-4alkyl) C(O)n(C1-4alkyl), —NHS(O)n(C1-4alkyl), —S(O)n(C1-4alkyl), —S(O)nNH(C1-4alkyl),
• —S(O)nN(C1-4alkyl3)(C1-4alkyl4) where C1-4alkyl3 and C1-4alkyl4 may be joined to form a heterocycloalkyl ring consisting of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, and Y′;
• Y and Y′ are independently selected at each occurrence from 3 to 8-membered carbocyclic or heterocyclic groups which are saturated, unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, mono- or di(C1-4)alkylamino, and C1-4alkylthio;
• wherein said 3- to 8-memberered heterocyclic groups contain one or more heteroatom(s) independently selected from N, O, and S;
• and
• n is independently chosen at each occurrence from 0, 1, and 2.

A compound of the Formula A, Formula B, Formula C, Formula D, Formula E, or Formula F:

• 220
• or a pharmaceutically acceptable salt of Formula A, Formula B, Formula C, Formula D, Formula E, or Formula F, wherein
• A represents NH or O;
• R3 and R4 are independently chosen at each occurrence from the group consisting of hydrogen, halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6;
• C2-6alkynyl substituted with 0-2 R6;
• C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6,
• —XR7, and Y;
• or any two
• R3 and R4 not attached to the same carbon may be joined to form an aryl ring substituted with 0-3 R6, a saturated or partially unsaturated carbocyclic ring of from 5 to 8 members, which carbocyclic ring is substituted with 0-2 R6, or a saturated, partially unsaturated, or aromatic heterocyclic ring of from 5 to 8 members, which heterocyclic ring is substituted with 0-2 R6 and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• R5 and R9 each represent from 1 to 3 substituents and are independently selected at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6, —XR7, and Y;
• R6 is independently selected at each occurrence from the group consisting of halogen, hydroxy, cyano, C1-4alkyl, C1-4alkoxy, —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —S(O)n(C1-4alkyl) halo(C1-4) alkyl, halo(C1-4) alkoxy, CO(C1-4alkyl), CONH(C1-4alkyl), CON(C1-4alkyl1)(C1-4alkyl2) where alkyl1 and alkyl2 may be joined to form a heterocycloalkyl ring of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, —XR7, and Y;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHR8—, —O—, —S(O)n—, —NH—, —NR8—, —C(═O)—, —C(═O)O—, —C(═O)NH—, —C(═O)NR8—, —S(O)nNH—, —S(O)nNR8—, NHC(═O)—, —NR8C(═O)—, —NHS(O)n—, and —NR8S(O)n—;
• R7 and R8 are independently selected at each occurrence from hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 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, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(C1-4alkyl)-NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl) —NHC(O)(C1-4alkyl), —N(C1-4alkyl)C(O)(C1-4alkyl) —NHS(O)n(C1-4alkyl), —S(O)n(C1-4alkyl), —S(O)nNH(C1-4alkyl), —S(O)nN(C1-4alkyl3)(C1-4alkyl4) where C1-4alkyl3 and C1-4alkyl4 may be joined to form a heterocycloalkyl ring consisting of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, and Y′;
• Y and Y′ are independently selected at each occurrence from 3- to 8-membered carbocyclic or heterocyclic groups which are saturated, unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, mono- or di(C1-4)alkylamino, and C1-4alkylthio;
• wherein said 3- to 8-memberered heterocyclic groups contain one or more heteroatom(s) independently selected from N, O, and S;
• and
• n is independently chosen at each occurrence from 0, 1, and 2.

A compound of the Formula:

• 227
• or a pharmaceutically acceptable salt thereof, wherein:
• A is absent or is selected from the group consisting of O, S, NRA, CRBRB′, NRACRBRB′, CRBRB′NRA, —CRA═CRB—, and C3H4;
• where RA, RB, and RB′ are independently selected at each occurrence from hydrogen or C1-6 alkyl;
• R3 and R4 are independently chosen at each occurrence from the group consisting of hydrogen, halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6;
• C2-6alkynyl substituted with 0-2 R6;
• C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-16alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6,
• —XR7, and Y;
• or any two
• R3 and R4 not attached to the same carbon may be joined to form an aryl ring substituted with 0-3 R6, a saturated or partially unsaturated carbocyclic ring of from 5 to 8 members, which carbocyclic ring is substituted with 0-2 R6, or a saturated, partially unsaturated, or aromatic heterocyclic ring of from 5 to 8 members, which heterocyclic ring is substituted with 0-2 R6 and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• R5 is selected from the group consisting of bromo, fluoro, iodo, halo(C1-6)alkyl, halo(C3-6)alkoxy, C3-6alkyl substituted with 0-3 R6, C2-6alkenyl substituted with 0-3 R6, C2-6alkynyl substituted with 0-3 R6, C3-6alkoxy substituted with 0-2 R6, (C3-8cycloalkyl)C1-4alkyl, —NH(C1-6alkyl) substituted with 0-2 R6, —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is substituted with 0-2 R6, Y, —(C═O)Y, —(CH2)Y, and —(CH(CN))Y;
• R9 is selected from the group consisting of halogen, cyano, —N(SO2C1-6alkyl)(SO2C1-6alkyl), —SO2NH2, halo (C1-6) alkyl, halo(C1-16)alkoxy, C1-6alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6,
• —N(C1-6alkyl)(C1-6alkyl) where each C1-6alkyl is substituted with 0-2 R6;
• R5B and R9B each represent from 0 to 2 substituents and are independently selected at each occurrence from the group consisting of halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl substituted with 0-2 R6, (C3-8cycloalkyl)C1-4alkyl substituted with 0-2 R6, C2-6alkenyl substituted with 0-2 R6, C2-6alkynyl substituted with 0-2 R6, C1-6alkoxy substituted with 0-2 R6, —NH(C1-6alkyl) substituted with 0-2 R6, and —N(C1-16alkyl)(C1-6alkyl) where each C1-6alkyl is independently substituted with 0-2 R6, and Y;
• and any two
• R5 and R5B bound to adjacent atoms may be joined to form a C3-8cycloalkyl group or a heterocycloalkyl group, each of which is optionally substituted by from 1 to 5 substituents independently chosen from cyano, halogen, hydroxy, C1-4alkyl, C1-4alkoxy, —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl) halo(C1-4)alkyl, and halo(C1-4)alkoxy, wherein the heterocycloalkyl group consists of from 4 to 8 atoms and contains 1, 2, or 3 heteroatoms selected from N, O, and S;
• R6 is independently selected at each occurrence from the group consisting of cyano, halogen, hydroxy, C1-4alkyl, C1-4alkoxy, —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —S(O)n(C1-4alkyl) halo(C1-4)alkyl, halo(C1-4)alkoxy, CO(C1-4alkyl), CONH(C1-4alkyl), CON(C1-4alkyl1)(C1-4alkyl2) where alkyl1 and alkyl2 may be joined to form a heterocycloalkyl ring of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, —XR7, and Y;
• X is independently selected at each occurrence from the group consisting of —CH2—, —CHR8—, —O—, —S(O)n—, —NH—, —NR8—, C(═O)—, —C(═O)NH—, —C(═O)NR8—, —S(O)nNH—, S(O)nNR8—, NHC(═O)—, —NR8C(═O)—, —NHS(O)n—, and —NR8S(O)n—;
• R7 and R8 are independently selected at each occurrence from hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 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, amino, cyano, nitro, haloalkyl, haloalkoxy, —O(C1-4alkyl), —NH(C1-4alkyl), —N(C1-4alkyl)(C1-4alkyl), —NHC(O)(C1-4alkyl), —N(C1-4alkyl)C(O)(C1-4alkyl), —NHS(O)n(C1-4alkyl), —S(O)n(C1-4alkyl), —S(O)nNH(C1-4alkyl), —S(O)nN(C1-4alkyl3)(C1-4alkyl4) where C1-4alkyl3 and C1-4alkyl4 may be joined to form a heterocycloalkyl ring consisting of from 5 to 8 ring atoms and containing 1, 2, or 3 heteroatoms selected from N, O, and S, and Y′;
• Y and Y′ are independently selected at each occurrence from 3- to 8-membered carbocyclic or heterocyclic groups which are saturated, unsaturated, or aromatic, which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, mono- or di(C1-4)alkylamino, and C1-4alkylthio;
• wherein said 3- to 8-memberered heterocyclic groups contain one or more heteroatom(s) independently selected from N, O, and S;
• and
• n is independently chosen at each occurrence from 0, 1, and 2.

A compound of the Formula:

• 230
• or a pharmaceutically acceptable salt thereof, wherein:
• A is absent or is selected from the group consisting of O, S, NRA, CRBRB′, NRACRBRB′, CRBRB′NRA, —CRA═CRB—, and C3H4;
• where RA, RB, and RB′ are independently selected at each occurrence from hydrogen or C1-6 alkyl;
• R3 and R4 are independently chosen at each occurrence from the group consisting of hydrogen, halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —NH(C1-6alkyl), and —N(C1-6alkyl)(C1-6alkyl)
• R5 is selected from the group consisting of halogen, halo(C1-6)alkyl, C3-6alkyl substituted with 0-3 R6, C2-6alkenyl substituted with 0-3 R6, (C3-8cycloalkyl)C1-4alkyl substituted with 0-3 R6, and Y;
• R5B and R9B each represent from 0 to 2 substituents and are independently chosen from halogen, cyano, nitro, halo(C1-2)alkyl, halo(C1-2)alkoxy, amino, C1-4alkyl, and C1-2alkoxy;
• R6 is independently selected at each occurrence from the group consisting of cyano, halogen, hydroxy, C1-4alkyl, C1-4alkoxy, —NH(C1-4alkyl), and —N(C1-4alkyl)(C1-4alkyl) and Y;
• Y is independently selected at each occurrence from C3-8 cycloalkyl, piperidinyl, piperazinyl, tetrahydropyranyl, dihydropyranyl, morpholinyl, thiomorpholinyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, thiazolyl, thienyl, and imidazolyl, each of which may be further substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, nitro, cyano, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, halo(C1-4)alkoxy, mono- or di(C1-4)alkylamino, and C1-4alkylthio.

A compound of the Formula:

• 232
• or a pharmaceutically acceptable salt thereof, wherein:
• A is absent or is selected from the group consisting of O, S, NRA, CRBRB′, NRACRBRB′, CRBRB′NRA, —CRA═CRB—, and C3H4;
• where RA, RB, and RB′ are independently selected at each occurrence from hydrogen or C1-6 alkyl;
• R3 and R4 are independently chosen at each occurrence from the group consisting of hydrogen, halogen, cyano, nitro, halo(C1-6)alkyl, halo(C1-6)alkoxy, hydroxy, amino, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, —NH(C1-6alkyl), and —N(C1-6alkyl)(C1-6alkyl);
• R5B, R5C, and R9B each represent from 0 to 2 substituents and are independently chosen from halogen, cyano, nitro, halo(C1-2)alkyl, halo(C1-2)alkoxy, amino, C1-4alkyl, and C1-2alkoxy;
• and
• R9 is selected from the group consisting of halogen, cyano, —N(SO2CH3) 2, —SO2NH2, halo(C1-3)alkyl, C1-3alkoxy, —NH(C1-3alkyl), and —N(C1-3alkyl)(C1-3alkyl)

A compound of the Formula

• 234
• or a pharmaceutically acceptable salt thereof wherein:
• R4 is methyl or hydrogen;
• R9B represents 0-2 substituents independently chosen from:
• halogen, cyano, nitro, halo(C1-2)alkyl, halo(C1-2)alkoxy, amino, C1-4alkyl, and C1-2alkoxy;
• and
• Ar1 is 2,4-dichlorphenyl or 3-nitro-4-chlorophenyl.

A compound of the Formula

• 235
• or a pharmaceutically acceptable salt thereof wherein:
• R9 is chloro or trifluoromethyl;
• and
• R5B and R9B independently represent from 0-2 substituents on each of the rings on which they occur and are independently chosen from:
• halogen, cyano, nitro, halo(C1-2)alkyl, halo(C1-2)alkoxy, amino, C1-4alkyl, and C1-2alkoxy.