Patent ID: 8937063
Filing Date: 2015-01-20
Classification: A61K,A61P,C07D

Abstract:
1. A method of reducing a serum or plasma level of at least one lipid selected from the group consisting of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein (a), comprising orally administering to a human in need thereof an effective amount of a niacin analog or a pharmaceutically acceptable salt thereof, wherein said oral administration is characterized by reduced flushing and reduced hepatocellular damage, as compared to oral administration of an equimolar dose of immediate-release niacin, wherein the niacin analog is represented by structure I: wherein A is a heterocyclyl or heteroaryl, optionally deuterated, containing from 5 to 12 ring atoms, including X and N, which is optionally substituted with 1-3 substituents, independently selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, halogen, nitro, cyano, sulfonic acid, alkylsulfoxyl, arylsulfoxyl, heteroarylsulfoxyl, aralkylsulfoxyl, heteroaralkylsulfoxyl, alkenylsulfoxyl, alkynylsulfoxyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, aralkylsulfonyl, heteroaralkylsulfonyl, alkenylsulfonyl, alkynylsulfonyl, hydroxyl, alkoxyl, aryloxyl, heteroaryloxyl, aralkyloxy, heteroaralkyloxy, alkenyloxy, alkynyloxy, thiol, alkylthio, arylthio, aralkylthio, heteroaralkylthio, alkenylthio, alkynylthio, formyl, acyl, formyloxy, acyloxy, formylthio, acylthio, amine, alkylamine, arylamine, heteroarylamine, aralkylamine, heteroaralkylamine, alkenylamine, alkynylamine, formylamine, acylamine, carboxyl, alkyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, aralkyloxycarbonyl, heteroaralkyloxycarbonyl, amido, alkylaminecarbonyl, arylaminecarbonyl, heteroarylaminecarbonyl, aralkylaminecarbonyl, and heteroaralkylaminecarbonyl; X is O, S, N or N(R Z is or an isostere of a carboxyl group; X X R is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, fused bicyclyl, carboxyalkyl, or arylalkenylaryl; R R R R m is 1, 2, 3, or 4; and peak concentration (C