Trpa1 antagonists

A method for treating a disorder or a condition wherein the disorder or condition is ameliorated by inhibiting TRPA1 in a subject in need of such treatment, comprising administering therapeutically effective amount of one or more compounds of formula (I),

• wherein
• R1 is pyridin-3-yl, pyridin-4-yl, thien-2-yl, thien-3-yl, isoquinolin-4-yl, quinolin-3-yl, or quinolin-4-yl;
• each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents as represented by Rj;
• Rj, at each occurrence, is independently alkyl, alkenyl, alkynyl, —CN, halogen, —ORa, —NO2, —N(Ra)(Rb), —N(Rb)C(O)R3, —N(Rb)S(O)2R1a, —N(Rb)C(O)OR3, —N(Rb)C(O)N(R3)(Rb), —N(Rb)S(O)2N(Ra)(Rb), —C(O)R1a, —C(O)ORa, —C(O)N(Ra)(Rb), —SRa, —SF5, —S(O)R1a, —S(O)2R13, —S(O)2OR1, —S(O)2N(Ra)(Rb), —(CRdRe)q—CN, haloalkyl, —(CRdRe)q—ORa, —(CRdRe)q—NO2, —(CRdRe)q—N(Ra)(Rb), —(CRdRe)q—N(Rb)C(O)Ra, —(CRdRe)q—N(Rb)S(O)2R1a, —(CRdRe)q—N(Re)C(O)ORa, —(CRdRe)q—N(Rb)C(O)N(Ra)(Rb), —(CRdRe)q—N(Re)S(O)2N(Ra)(Rb), —(CRdRe)q—C(O)Ra, —(CRdRe)q—C(O)ORa, —(CRdRe)q—C(O)N(R3)(Rb), —(CRdRe)q—S(O)2R1a, —(CRdRe)q—S(O)2OR1a, and —(CRdRe)q—S(O)2N(Rd)(Re);
• R2 is hydrogen, C1-6 alkyl, or haloalkyl;
• R3 is C1-6 alkyl, haloalkyl, or cyclopropyl;
• wherein the cyclopropyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the groups consisting of alkyl, halogen, and haloalkyl;
• Y is —ORf, —N(Rf)(Rg), —N(Rf)C(O)Rg, —N(Rf)S(O)2Rg, or —N(Rf)C(O)N(Rf)(Rg);
• R1a, at each occurrence, is independently alkyl or haloalkyl;
• Ra and Rb, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• Rd and Re, at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl;
• Rf and Rg, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• and
• q is 1, 2, 3, or 4;
• or a solvate, a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or any combination thereof.

A method for treating pain in a subject in need of such treatment, comprising administering therapeutically effective amount of one or more compounds of formula (I)

• wherein
• R1 is pyridin-3-yl, pyridin-4-yl, thien-2-yl, thien-3-yl, isoquinolin-4-yl, quinolin-3-yl, or quinolin-4-yl;
• each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents as represented by Rj;
• Rj, at each occurrence, is independently alkyl, alkenyl, alkynyl, —CN, halogen, —ORa, —NO2, N(Ra)(Rb), N(Rb)C(O)3, —N(Rb)S(O)2R1a, —N(Rb)C(O)ORa, —N(Rb)C(O)N(Ra)(Rb), —N(Rb)S(O)2N(Ra)(Rb), —C(O)Ra, —C(O)ORa, —C(O)N(Ra)(Rb), —SRa, —SF5, —S(O)R1a, —S(O)2R1a, —S(O)2OR1a, —S(O)2N(Ra)(Rb), —(CRdRe)q—CN, haloalkyl, —(CRdRe)q—ORa, —(CRdRe)q—NO2, —(CRdRe)q—N(Ra)(Rb), —(CRdRe)q—N(Rb)C(O)Ra, (CRdRe)q—N(Rb)S(O)2R1, —(CRdRe)q—N(Rb)C(O)ORa, (CRdRe)q—N(Rb)C(O)N(Ra)(Rb), —(CRdRe)q—N(Rb)S(O)2N(Ra)(Rb), —(CRdRe)q—C(O)Ra, —(CRdRe)q—C(O)ORa, —(CRdRe)q—C(O)N(Ra)(Rb), —(CRdRe)q—S(O)2R1a, —(CRdRe)q—S(O)2OR1a, and —(CRdRe)q—S(O)2N(Ra)(Re);
• R2 is hydrogen, C1-6 alkyl, or haloalkyl;
• R3 is C1-6 alkyl, haloalkyl, or cyclopropyl;
• wherein the cyclopropyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the groups consisting of alkyl, halogen, and haloalkyl;
• Y is —ORf, —N(Rf)(Rg), —N(Rf)C(O)Rg, —N(Rf)S(O)2Rg, or —N(Rf)C(O)N(Rf)(Rg);
• R1a, at each occurrence, is independently alkyl or haloalkyl;
• Ra and Rb, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• Rd and Re, at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl;
• Rf and Rg, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• and
• q is 1, 2, 3, or 4;
• or a solvate, a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or any combination thereof.

A pharmaceutical composition comprising therapeutically effective amount of one or more compounds of formula (I)

• wherein
• R1 is pyridin-3-yl, pyridin-4-yl, thien-2-yl, thien-3-yl, isoquinolin-4-yl, quinolin-3-yl, or quinolin-4-yl;
• each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents as represented by Rj;
• Rj at each occurrence, is independently alkyl, alkenyl, alkynyl, —CN, halogen, —ORa, —NO2, N(Ra)(Rb), —N(Rb)C(O)Ra, —N(Rb)S(O)2Ra, —N(Rb)C(O)ORa, —N(Rb)C(O)N(Ra)(Rb), —N(Rb)S(O)2N(Ra)(Rb), —C(O)R3, —C(O)OR3, —C(O)N(Ra)(Rb), —SRa, —SF5, —S(O)R1a, —S(O)2R13, —S(O)2ORa, —S(O)2N(Ra)(Rb), —(CRdRe)q—CN, haloalkyl, —(CRdRe)q—ORa, (CRdRe)q—NO2, (CRdRe)q—N(Ra)(Rb), (CRdRe)q—N(Rb)C(O)Ra, (CRdRe)q—N(Rb)S(O)2R1a, —(CRdRe)q—N(Rb)C(O)ORa, —(CRdRe)q—N(Rb)C(O)N(Ra)(Rb), —(CRdRe)q—N(Rb)S(O)2N(Ra)(Rb), (CRdRe)q—C(O)Ra, —(CRdRe)q—C(O)OR3—(CRdRe)q—C(O)N(Ra)(Re), (CRdRe)q—S(O)2R1a, —(CRdRe)q—S(O)2OR1a, and —(CRdRe)q—S(O)2N(Ra)(Re);
• R2 is hydrogen, C1-6 alkyl, or haloalkyl;
• R3 is C1-6 alkyl, haloalkyl, or cyclopropyl;
• wherein the cyclopropyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the groups consisting of alkyl, halogen, and haloalkyl;
• Y is —ORf, —N(Rf)(Rg), —N(Rf)C(O)Rg, —N(Rf)S(O)2Rg, or —N(Rf)C(O)N(Rf)(Rg);
• R1a, at each occurrence, is independently alkyl or haloalkyl;
• Ra and Rb, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• Rd and Re, at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl;
• Rf and Rg, at each occurrence, are each independently hydrogen, alkyl, or haloalkyl;
• and
• q is 1, 2, 3, or 4;
• or a solvate, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.