Compounds useful as modulators of TRPM8

摘要

The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formula (I) and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.;

主权项

1. A compound having a structural Formula (II): or a salt or solvate thereof, wherein Ar is optionally substituted aryl, optionally substituted carbocyclyl, or optionally substituted heteroaryl; Y is oxygen or sulfur; Z is nitrogen or CR; R is hydrogen or lower alkyl; X1—X2 is O—CR2aR2b, or CR5═CR6; R2a, R2b, R5, and R6 are independently hydrogen or lower alkyl; R1 is an optionally substituted group selected from the group consisting of pyrrolyl, furanyl, thienyl, and pyrazolyl; n is 0, 1, 2, or 3; and each R2 is independently optionally substituted alkyl, optionally substituted heteroalkyl, optionally substituted alkenyl, alkoxy, hydroxyl, amino, N-alkyl amino, N-dialkyl amino, halo, nitro, cyano, acyl, carboxyl, carboxyl ester, or amide, wherein each optional substituent is selected from the group consisting of alkyl, heteroalkyl, alkenyl, alkoxy, hydroxyl, amino, N-alkyl amino, N-dialkyl amino, halo, nitro, cyano, acyl, carboxyl, carboxyl ester, or amide; or two substituents, together with the atoms to which they are attached, form a carbocyclyl optionally substituted with alkyl or alkoxy; or two substituents, together with the atoms to which they are attached, form a heterocyclyl containing one or more heteroatom(s) selected from nitrogen, oxygen, and sulfur.