The design and synthesis of potent, selective benzodiazepine sulfonamide bombesin receptor subtype 3 (BRS-3) agonists with an increased barrier of atropisomerization

  • Bioorg Med Chem. 2012 May 1;20(9):2845-9. doi: 10.1016/j.bmc.2012.03.029.
Harry R Chobanian  1 ,  Yan Guo ,  Ping Liu ,  Thomas J Lanza Jr ,  Marc Chioda ,  Linda Chang ,  Theresa M Kelly ,  Yanqing Kan ,  Oksana Palyha ,  Xiao-Ming Guan ,  Donald J Marsh ,  Joseph M Metzger ,  Katie Raustad ,  Sheng-Ping Wang ,  Alison M Strack ,  Judith N Gorski ,  Randy Miller ,  Jianmei Pang ,  Kathy Lyons ,  Jasminka Dragovic ,  Jian G Ning ,  Wes A Schafer ,  Christopher J Welch ,  Xiaoyi Gong ,  Ying-Duo Gao ,  Viktor Hornak ,  Marc L Reitman ,  Ravi P Nargund ,  Linus S Lin
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. [email protected]
PMID: 22494842 DOI: 10.1016/j.bmc.2012.03.029
Abstract

Bombesin Receptor subtype 3 (BRS-3) is an orphan G-protein coupled receptor expressed primarily in the hypothalamus which plays a role in the onset of both diabetes and Obesity. We report herein our progress made towards identifying a potent, selective Bombesin Receptor subtype-3 (BRS-3) agonist related to the previously described MK-7725(1) Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position. This would thereby make clinical development of this class of compounds more cost effective by inhibiting racemization which can occur over long periods of time at room/elevated temperature.