GLUCOSE METABOLISM MODULATING COMPOUNDS

摘要

The present invention provides, inter alia, dihydropyridone compounds and compositions, including analogs of a vesicular monoamine transporter type 2 (VMAT2) antagonist. The present invention also provides methods of using such compounds/analogs for modulating glucose levels, and/or preventing, treating, or ameliorating the effects of diabetes and hyperglycemia.

主权项

1. A compound of formula I: wherein R1, R2, R3, R6, and R7 are independently selected from the group consisting of H, halogen, hydroxyl, C1-8alkyl, C1-8alkenyl, C1-8alkynyl, C1-8alkoxy, 3- to 8-membered carbocyclic or heterocyclic, aryl, heteroaryl, C1-4aralkyl, residues of glycolic acid, ethylene glycol/propylene glycol copolymers, carboxylate, ester, amide, carbohydrate, amino acid, alditol, OC(X)2COOH, SC(X)2COOH, NHCHXCOOH, COY, CO2Y, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, thioalkyl, thioester, propylphthalimide, and thioether; R4 and R5, which are attached to one or more positions of at least one carbon atom of the respective rings, are independently selected from the group consisting of H, halogen, hydroxyl, C1-8alkyl, C1-8alkenyl, C1-8alkynyl, C1-8alkoxy, 3- to 8-membered carbocyclic or heterocyclic, aryl, heteroaryl, C1-4aralkyl, residues of glycolic acid, ethylene glycol/propylene glycol copolymers, carboxylate, ester, amide, carbohydrate, amino acid, alditol, OC(X)2COOH, SC(X)2COOH, NHCHXCOOH, COY, CO2Y, sulfate, sulfonamide, sulfoxide, sulfonate, sulfone, thioalkyl, thioester, propylphthalimide, and thioether; X is selected from the group consisting of H, C1-8alkyl, C1-8alkenyl, C1-8alkynyl, carbocycle, aryl, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, and alkylheterocycle, wherein each alkyl, carbocycle, aryl, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, and alkylheterocycle is optionally substituted with at least one substituent; Y is selected from the group consisting of H, C1-8alkyl, C1-8alkenyl, C1-8alkynyl, aryl, carbocycle, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, alkylheterocycle, and heteroaromatic, wherein each alkyl, alkenyl, alkynyl, aryl, carbocycle, heteroaryl, heterocycle, alkylaryl, alkylheteroaryl, alkylheterocycle, and heteroaromatic is optionally substituted with at least one substituent; and --- is an optional bond, wherein the optional bond is a single bond or a double bond;or an enantiomer, optical isomer, diastereomer, N-oxide, crystalline form, hydrate, or pharmaceutically acceptable salt thereof.