COMPOUNDS FOR THE TREATMENT OF OBESITY AND METHODS OF USE THEREOF

摘要

Weight loss agents include compounds defined by Formula I or a pharmaceutically acceptable salt or prodrug thereof, compositions containing the same, and methods of use thereof are described herein. In some embodiments, the compound is Withaferin A. In other embodiments, the compound is Michael addition product of Withaferin A. The compounds can be administered to induce weight loss in a pre-obese, obese, or morbidly obese patient, reduce body fat in a pre-obese, obese, or morbidly obese patient, reduce food intake in a pre-obese, obese, or morbidly obese patient, improve glucose homeostasis in a pre-obese, obese, or morbidly obese patient, or combinations thereof.;

主权项

1. A pharmaceutical formulation comprising a compound defined by Formula I: wherein R1-R7 are independently hydrogen, carboxylic acid (—COOH), formyl, acyl, primary amide (e.g., —CONH2), secondary amide (e.g., —CONHR8), tertiary amide (e.g., —CONR8R8), secondary carbamate (e.g., —OCONHR8; —NHCOOR8), tertiary carbamate (e.g., —OCONR8R8; —NR8COOR7), urea (e.g., —NHCONHR8; —NR8CONHR8; —NHCONR8R8, —NR8CONR8R8), carbinol (e.g., —CH2OH; —CHR8OH, —CR8R8OH), ether (e.g., —OR8), ester (e.g., —COOR8), alcohol (—OH), thiol (—SH), primary amine (—NH2), secondary amine (e.g., —NHR8), tertiary amine (e.g., —NR8R8), thioether (e.g., —SR8), sulfinyl group (e.g., —SOR8), sulfonyl group (e.g., —SOOR8), sulfino group, halogen, nitrile, or CF3; or an alkyl, cycloalkyl, heterocycloalkyl, alkylaryl, alkenyl, alkynyl, aryl, or heteroaryl group optionally substituted with between one and five substituents individually selected from alkyl, cyclopropyl, cyclobutyl ether, amine, halogen, hydroxyl, ether, nitrile, CF3, ester, amide, urea, carbamate, thioether, carboxylic acid, and aryl; R8, when present, is individually for each occurrence an alkyl, cycloalkyl, heterocycloalkyl, alkylaryl, alkenyl, alkynyl, aryl, or heteroaryl group, optionally substituted with between one and five substituents individually selected from alkyl, cyclopropyl, cyclobutyl ether, amine, halogen, hydroxyl, ether, nitrile, CF3, ester, amide, urea, carbamate, thioether, carboxylic acid, and aryl; wherein the dotted line represents a single or double bond; or a pharmaceutically acceptable salt or prodrug thereof, wherein the compound is present in a therapeutically effective amount to induce weight loss in a pre-obese, obese, or morbidly obese patient; reduce body fat in a pre-obese, obese, or morbidly obese patient; reduce food intake in a pre-obese, obese, or morbidly obese patient; improve glucose homeostasis in a pre-obese, obese, or morbidly obese patient; or combinations thereof.