Discovery of pyrazolyl propionyl cyclohexenamide derivatives as full agonists for the high affinity niacin receptor GPR109A

  • Bioorg Med Chem Lett. 2010 Jun 1;20(11):3372-5. doi: 10.1016/j.bmcl.2010.04.013.
Fa-Xiang Ding  1 ,  Hong C Shen ,  Larrisa C Wilsie ,  Mihajlo L Krsmanovic ,  Andrew K Taggart ,  Ning Ren ,  Tian-Quan Cai ,  Junying Wang ,  Xinchun Tong ,  Tom G Holt ,  Qing Chen ,  M Gerard Waters ,  Milton L Hammond ,  James R Tata ,  Steven L Colletti
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. [email protected]
PMID: 20452209 DOI: 10.1016/j.bmcl.2010.04.013
Abstract

A series of pyrazolyl propionyl cyclohexenamides were discovered as full agonists for the high affinity niacin receptor GPR109A. The structure-activity relationship (SAR) studies were aimed to improve activity on GPR109A, reduce Cytochrome P450 2C8 (CYP2C8) and Cytochrome P450 2C9 (CYP2C9) inhibition, reduce serum shift and improve pharmacokinetic (PK) profiles.