TRPV1 antagonists

A compound having formula (I) or pharmaceutically acceptable salt, solvate, or a combination thereof

• wherein
• one of X1, X2, X3, and X4 is C, and the others are C(Ra);
• wherein each Ra is the same or different, and is independently hydrogen, —CN, NO2, alkyl, halogen, haloalkyl, ORx, or N(Rx)2;
• J is CR3J;
• K is N;
• L is NR3L;
• is a double bond;
• R3L is hydrogen, alkyl, or haloalkyl;
• R3J is hydrogen, alkyl, halogen, haloalkyl, ORx, or N(Rx)2;
• X5-X6 is CR3aR3b, C(R3R4)C(R5R6), CR7═CR8, or C(R9R10)C(R11R12)C(R13R14);
• R4, R6, R7, R8, R10, R12, and R14, are the same or different, and are each independently hydrogen, alkyl, or haloalkyl;
• R3a and R3b are each independently hydrogen, alkyl, halogen, or haloalkyl;
• R3, R5, R9, R11, and R13, are the same or different, and are each independently hydrogen, —CN, alkyl, halogen, haloalkyl, ORx, or N(Rx)2;
• R3 and R5, together with the carbon atoms to which they are attached, optionally form a C3-C6 cycloalkyl that is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of alkyl, halogen, and haloalkyl;
• m is 0, 1, 2, 3, or 4;
• each Rb is an optional substituent and at each occurrence, is independently —CN, alkyl, halogen, haloalkyl, ORx, or N(Rx)2;
• each Rx is independently hydrogen, alkyl, or haloalkyl;
• ring G2 is aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, each of which is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, oxo, haloalkyl, CN, NO2, —ORf, —OC(O)Re, —OC(O)N(Rf)(Rg), —SRf, —S(O)2Re, —S(O)2N(Rf)(Rg), —C(O)Rf, —C(O)ORf, —C(O)N(Rf)(Rg), —N(Rf)(Rg), —N(Rg)C(O)Re, —N(Rg)S(O)2Re, —N(Rg)C(O)O(Re), —N(Rg)C(O)N(Rf)(Rg), Ga, —(C1-C6 alkylenyl)-ORf, —(C1-C6 alkylenyl)-OC(O)Re, —(C1-C6 alkylenyl)-OC(O)N(Rf)(Rg), —(C1-C6 alkylenyl)-S(O)2Re, —(C1-C6 alkylenyl)-S(O)2N(Rf)(Rg), —(C1-C6 alkylenyl)-C(O)Rf, —(C1-C6 alkylenyl)-C(O)ORf, —(C1-C6 alkylenyl)-C(O)N(Rf)(Rg), —(C1-C6 alkylenyl)-N(Rf)(Rg), —(C1-C6 alkylenyl)-N(Rg)C(O)Re, —(C1-C6 alkylenyl)-N(Rg)S(O)2Re, —(C1-C6 alkylenyl)-N(Rg)C(O)O(Re), —(C1-C6 alkylenyl)-N(Rg)C(O)N(Rf)(Rg), —(C1-C6 alkylenyl)-CN, and —(C1-C6 alkylenyl)-Ga;
• Re, at each occurrence, is independently alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, Ga, or —(C1-C6 alkylenyl)-Ga;
• Rf, at each occurrence, is independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, Ga, or —(C1-C6 alkylenyl)-Ga;
• Rg, at each occurrence, is independently hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, benzyl, or monocyclic cycloalkyl;
• Ga, at each occurrence, is independently aryl, heteroaryl, cycloalkyl, cycloalkenyl, or heterocycle, each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, halogen, haloalkyl, —CN, oxo, —ORh, —OC(O)Ri, —OC(O)N(Rh)2, —SRh, —S(O)2Ri, —S(O)2N(Rh)2, —C(O)Rh, —C(O)ORh, —C(O)N(Rh)2, —N(Rh)2, —N(Rh)C(O)Ri, —N(Rh)S(O)2Ri, —N(Rh)C(O)O(Ri), —N(Rh)C(O)N(Rh)2, —(C1-C6 alkylenyl)-ORf, —(C1-C6 alkylenyl)-OC(O)Ri, —(C1-C6 alkylenyl)-OC(O)N(Rh)2, —(C1-C6 alkylenyl)-S(O)2Ri, —(C1-C6 alkylenyl)-S(O)2N(Rh)2, —(C1-C6 alkylenyl)-C(O)Rh, —(C1-C6 alkylenyl)-C(O)ORh, —(C1-C6 alkylenyl)-C(O)N(Rh)2, —(C1-C6 alkylenyl)-N(Rh)2, —(C1-C6 alkylenyl)-N(Rh)C(O)Ri, —(C1-C6 alkylenyl)-N(Rh)S(O)2Ri, —(C1-C6 alkylenyl)-N(Rh)C(O)O(Ri), —(C1-C6 alkylenyl)-N(Rh)C(O)N(Rh)2, and —(C1-C6 alkylenyl)-CN;
• Rh, at each occurrence, is independently hydrogen, alkyl, or haloalkyl;
• and
• Ri, at each occurrence, is independently alkyl or haloalkyl.