Acyl hydroxypyrazoles as novel agonists for high-affinity nicotinic acid receptor GPR109A: WO2008051403.
BACKGROUND
Acyl hydroxypyrazoles were discovered and claimed by Merck as novel agonists for the high-affinity nicotinic acid receptor, G-protein coupled receptor 109A (GPR109A). The fused bicyclic core contains a hydroxypyrazole that mimics the anthranilide moiety described in their earlier patents and patent publications.


OBJECTIVE
This article evaluates new GPR109A receptor agonists disclosed by Merck in the recent patent WO2008051403.


CONCLUSIONS
The aim of this invention was to provide potential therapy to reduce free fatty acids (FFA), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and serum triglycerides (TG), and to raise high-density lipoprotein cholesterol (HDL-C). Thus, these agonists could - potentially - be used to treat dyslipidemia, atherosclerosis, and metabolic syndromes such as diabetes.
Shen
Hong C
HC
Research Fellow Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. hong_shen@merck.com
D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D010330:Patents as Topic; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D011978:Receptors, Nicotinic; D013329:Structure-Activity Relationship
D005230:Fatty Acids, Nonesterified; C530636:HCAR2 protein, human; D011720:Pyrazoles; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic