2. Academic Validation
  3. Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor

Discovery of biaryl anthranilides as full agonists for the high affinity niacin receptor

  • J Med Chem. 2007 Dec 13;50(25):6303-6. doi: 10.1021/jm700942d.
Hong C Shen 1,  Fa-Xiang Ding,  Silvi Luell,  Michael J Forrest,  Ester Carballo-Jane,  Kenneth K Wu,  Tsuei-Ju Wu,  Kang Cheng,  Larissa C Wilsie,  Mihajlo L Krsmanovic,  Andrew K Taggart,  Ning Ren,  Tian-Quan Cai,  Qiaolin Deng,  Qing Chen,  Junying Wang,  Michael S Wolff,  Xinchun Tong,  Tom G Holt,  M Gerard Waters,  Milton L Hammond,  James R Tata,  Steven L Colletti
Affiliations

Affiliation

  • 1 Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey 07065-0900, USA. hong_shen@merck.com
PMID: 17994679 DOI: 10.1021/jm700942d
Abstract

Biaryl anthranilides are reported as potent and selective full agonists for the high affinity niacin receptor GPR109A. The SAR presented outlines approaches to reduce serum shift and both CYPCYP2C8 and CYP2C9 liabilities, while improving PK and maintaining excellent receptor activity. Compound 2i exhibited good in vivo antilipolytic efficacy while providing a significantly improved therapeutic index over vasodilation (flushing) with respect to niacin in the mouse model.

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