Patent ID: 9067935
Filing Date: 2015-06-30
Classification: A61K,A61P,C07D

Abstract:
1. A method for treating a disease, disorder, or condition that is affected by the modulation of TRPM8, comprising the step of administering to a mammal in need of such treatment a therapeutically effective amount of a TRPM8 antagonist of Formula (I) wherein i) C1-6alkyl wherein C1-6alkyl is unsubstituted or substituted with one substituent that is C3-6cycloalkyl or trifluoromethyl; or ii) phenylmethyl wherein the phenyl ring is unsubstituted or substituted with one to three substituents each of which is independently selected from the group consisting of chloro, fluoro, bromo, C1-4alkyl, C1-4alkoxy, trifluoromethoxy, C1-4alkoxycarbonyl, C1-3alkylthio, trifluoromethylthio, cyano, trifluoromethyl, C1-3 alkylsulfonyl, trifluoromethylsulfonyl, and C1-3 alkylcarbonyl; with the proviso that not more than two of the substituents are selected from the group consisting of C1-4alkoxy, trifluoromethoxy, C1-4 alkoxycarbonyl, C1-3alkylthio, trifluoromethylthio, cyano, trifluoromethyl, C1-3 alkylsulfonyl, trifluoromethylsulfonyl, and C1-3 alkylcarbonyl; i) C1-3alkyl wherein C1-3alkyl is unsubstituted or substituted with one substituent selected from the group consisting of carboxy, methoxycarbonyl, trifluoromethyl, and methoxy; ii) —(CH2)2NRARB wherein RA and RB are each independently C1-6alkyl; or, RA and RB are taken together with the nitrogen atom to which they are attached to form piperidin-1-yl; iii) phenyl substituted at the 4-position with pyrazolyl; wherein the point of attachment of the heteroaryl is through a nitrogen heteroatom; iv) phenyl wherein phenyl is unsubstituted or substituted with one or two substituents each of which is independently selected from the group consisting of chloro, fluoro, bromo, C1-4alkoxy, C1-4alkoxycarbonyl, carboxy, and C1-3 alkyl; or v) pyridin-3-yl substituted at the 6-position with morpholin-4-yl; provided that a compound of Formula (I) is other than the compound wherein Y is methyl, R1 is 4-trifluoromethoxyphenylmethyl, R2 is 7-trifluoromethyl, and R3 is phenyl; or the compound wherein Y is hydrogen, R1 is 4-trifluoromethoxyphenylmethyl, R2 is 6-chloro, and R3 is 4-carboxyphenyl; and enantiomers, diastereomers, and pharmaceutically acceptable salt forms thereof.