Trpa1 antagonists for use in the treatment of atopic dermatitis

A method for preventing and/or treating the inflammatory component of atopic dermatitis in a subject in need thereof, comprising administering to the subject a TRPA1 receptor antagonist;

• wherein the TRPA1 receptor antagonist is selected from the group consisting of a compound of formula (II), (III), (IV), (V), (VI), (VII), (VIII), and (IX), or salts, tautomers, or enantiomers thereof:
• wherein R6, R7, and R8 are identical or different, and are selected from H, C1-C12 alkyl, CF3, O—C1-C12 alkyl, or —O-cyclopropylmethyl;
• wherein:
• R1 is C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, or phenyl group, wherein the cycloalkyl and phenyl groups are optionally substituted with 1 or 2 substituent(s) each independently selected from halogen, C1-C2 alkyl, or C1-C2 alkoxy group;
• R2 is C1-C2 alkyl group;
• R3 is C1-C2 alkyl group;
• R4 is H, halogen, C1-C2 alkoxy, or C1-C2 haloalkyl group;
• and
• R5 is H, halogen, C1-C2 alkyl, C1-C2 alkoxy, C1-C2 haloalkyl, C1-C2 haloalkoxy, or C1-C2 alkylthio group;
• wherein R1 and R2 are each independently selected from H, halogen, OH, CH3, CF3, OCH3, or CN group;
• wherein:
• R1 is selected from (CHR2)nC5-C10 heterocyclyl, (CHR2)nC6-C10 aryl, (CHR2)nC3-C10 cycloalkyl, or C1-C6 alkyl group;
• wherein the heterocyclyl, aryl, cycloalkyl, and alkyl groups are optionally substituted with 1 to 3 groups of R3;
• and n is an integer from 0 to 20;
• and
• R2 and R3, when present, are each independently a methyl or a halogen;
• wherein:
• B is a 6-membered heteroaryl group, wherein the heteroaryl group is optionally substituted with one or more groups independently selected from halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, O—C1-C6 alkyl, O—C1-C6 haloalkyl, 5 or 6-membered heteroaryl, C3-C7 cycloalkyl, and 4, 5, 6 or 7-membered heterocyclyl group;
• wherein the 5 or 6-membered heteroaryl, C3-C7 cycloalkyl, and 4, 5, 6 or 7-membered heterocyclyl groups are optionally substituted with one or more groups independently selected from halogen, CN, C1-C6 alkyl, C1-C6 haloalkyl, O—C1-C6 alkyl, and O—C1-C6 haloalkyl group;
• R1 is phenyl or heteroaryl group, wherein the phenyl and heteroaryl groups are optionally substituted with one or more groups independently selected from halogen, CN, C1-C6 alkyl, and C1-C6 haloalkyl group;
• R2 is phenyl, C3-C7 cycloalkyl, 5 or 6-membered heteroaryl, or 4, 5, 6 or 7-membered heterocycle, wherein the phenyl, cycloalkyl, 5 or 6-membered heteroaryl, and 4, 5, 6 or 7-membered heterocycle groups are optionally substituted with one or more groups independently selected from halogen, CN, SF5, C1-C6 alkyl, C1-C6 haloalkyl, O—C1-C6 alkyl, and O—C1-C6 haloalkyl;
• wherein:
• R1 is selected from H, OH, OMe, or halogen;
• and
• A is selected from:
• wherein:
• A is a heteroatom or C(═O);
• and
• B is a carbon atom or heteroatom, wherein the carbon atom is optionally linked to a halogen;
• and