Antagonists to the vanilloid receptor subtype 1 (VR1) and uses thereof

A compound having formula (I)

• or a pharmaceutically acceptable salt, prodrug, salt of a prodrug thereof, wherein
• R1, R2 and R3 are independently selected from the group consisting of hydrogen, halogen, alkyl and haloalkyl;
• L is a bond or C1-6 alkyl;
• A is a ring selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl;
• wherein each A is independently substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, cyano, hydroxyl, alkoxy, haloalkoxy, —SH, —S(alkyl), —S(O)alkyl, —S(O)2alkyl, —S(O)2NH2, —S(O)2N(H)alkyl, —S(O)2N(alkyl)2, —NH2, —N(H)alkyl, —N(alkyl)2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)N(H)alkyl, —C(O)N(alkyl)2, haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSH, -alkylS(alkyl), -alkylS(O)alkyl, -alkylS(O)2alkyl, -alkylS(O)2NH2, -alkylS(O)2N(H)alkyl, -alkylS(O)2N(alkyl)2, -alkylNH2, -alkylN(H)alkyl, -alkylN(alkyl)2, -alkylC(O)OH, -alkylC(O)O(alkyl), -alkylC(O)alkyl, -alkylC(O)NH2, -alkylC(O)N(H)alkyl, and -alkylC(O)N(alkyl)2;
• G is a ring selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl;
• wherein each G is independently substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, cyano, halogen, —ORa, —OC(O)Ra, —OC(O)NRaRb, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)2NRaRb, —NRaRb, —C(O)ORa, —C(O)Ra, —C(O)NRaRb, Rc, haloalkyl, cyanoalkyl, -alkylORa, -alkylOC(O)Ra, -alkylOC(O)NRaRb, -alkylSRa, -alkylS(O)Ra, -alkylS(O)2Ra, -alkylS(O)2NRaRb, -alkylNRaRb, -alkylC(O)ORa, -alkylC(O)Ra, -alkylC(O)NRaRb, and -alkyl-Rc;
• Ra, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, arylalkyl and heteroarylalkyl;
• wherein the cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, aryl moiety of the arylalkyl and the heteroaryl moiety of the heteroarylalkyl are independently substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, haloalkyl, cyanoalkyl, hydroxyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, —SH, —S(alkyl), —S(O)alkyl, —S(O)2alkyl, —S(O)2NH2, —S(O)2N(H)alkyl, —S(O)2N(alkyl)2, —NH2, —N(H)alkyl, —N(alkyl)2, —C(O)OH, —C(O)O(alkyl) —C(O)O(aryl), —C(O)alkyl, —C(O)NH2, —C(O)N(H)alkyl, and —C(O)N(alkyl)2;
• Rb, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle, heteroaryl, arylalkyl and heteroarylalkyl;
• wherein each of the cycloalkyl, aryl, heterocycle, heteroaryl, aryl moiety of the arylalkyl and heteroaryl moiety of the heteroarylalkyl is independently substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, haloalkyl, cyanoalkyl, hydroxyl, alkoxy, haloalkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, —SH, —S(alkyl), —S(O)alkyl, —S(O)2alkyl, —S(O)2NH2, —S(O)2N(H)alkyl, —S(O)2N(alkyl)2, —NH2, —N(H)alkyl, —N(alkyl)2, —C(O)OH, —C(O)O(aryl), —C(O)alkyl, —C(O)NH2, —C(O)N(H)alkyl, and —C(O)N(alkyl)2;
• and
• Rc, at each occurrence, is a ring independently selected from the group consisting of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl;
• wherein each Rc is independently substituted with 0, 1, 2, 3, 4 or 5 substituents selected from the group consisting of alkyl, halogen, cyano, hydroxyl, alkoxy, haloalkoxy, —SH, —S(alkyl), —S(O)alkyl, —S(O)2alkyl, —S(O)2NH2, —S(O)2N(H)alkyl, —S(O)2N(alkyl)2, —NH2, —N(H)alkyl, —N(alkyl)2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)N(H)alkyl, —C(O)N(alkyl)2;
• haloalkyl, cyanoalkyl, hydroxyalkyl, alkoxyalkyl, haloalkoxyalkyl, -alkylSH, -alkylS(alkyl), -alkylS(O)alkyl, -alkylS(O)2alkyl, -alkylS(O)2NH2, -alkylS(O)2N(H)alkyl, -alkylS(O)2N(alkyl)2, -alkylNH2, -alkylN(H)alkyl, -alkylN(alkyl)2, -alkylC(O)OH, -alkylC(O)O(alkyl), -alkylC(O)alkyl, -alkylC(O)NH2, -alkylC(O)N(H)alkyl, and -alkylC(O)N(alkyl)2.