Vanilloid fatty hydroxamates as therapeutic anti-inflammatory pharmaceuticals

摘要

Three unique subtypes of N-hydroxyamides and N-hydroxycarbamates containing both the vanilloid moiety (4-hydroxy-3-methoxybenzyl) and a lipophilic aliphatic moiety. Also disclosed are direct syntheses of these vanilloid fatty hydroxamates. The compounds possess inhibitory activity against the enzymes fatty acid amide hydrolase (FAAH) and matrix metallo-proteinase 9 (MMP-9). In addition, these substances bind to the calcium channel protein TRPV1 and inhibit vesicant-induced inflammation in skin and cornea. The compounds have utility in treating topical or systemic inflammatory processes in the skin and/or eye.

主权项

1. A vanilloid fatty N-hydroxy amide or vanilloid fatty N-hydroxy carbamate compound represented by Formula (V): wherein when (1) X is N(OH) and Y is C(═O)O, or (2) X is N(OH) and Y is C(═O), R is a lipophilic moiety selected from the group consisting of unsubstituted linear alkyl, branched alkyl, optionally branched cycloalkyl, linear alkenyl, branched alkenyl, optionally branched cycloalkenyl, linear alkynyl, branched alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, and optionally substituted arylalkyl; and when (3) X is C(═O) and Y is N(OH), R is a lipophilic moiety selected from the group consisting of unsubstituted linear alkyl, branched alkyl, optionally branched cycloalkyl, linear alkenyl, branched alkenyl, and optionally branched cycloalkenyl; or the compounds of Formula (V) are prodrugs or pharmaceutically acceptable salts thereof.