1021937-86-9Relevant articles and documents
Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity
Liu, Jian,He, Shuwen,Jian, Tianying,Dobbelaar, Peter H.,Sebhat, Iyassu K.,Lin, Linus S.,Goodman, Allan,Guo, Cheng,Guzzo, Peter R.,Hadden, Mark,Henderson, Alan J.,Pattamana, Kevin,Ruenz, Megan,Sargent, Bruce J,Swenson, Brian,Yet, Larry,Tamvakopoulos, Constantin,Peng, Qianping,Pan, Jie,Kan, Yanqing,Palyha, Oksana,Kelly, Theresa M.,Guan, Xiao-Ming,Howard, Andrew D.,Marsh, Donald J.,Metzger, Joseph M.,Reitman, Marc L.,Wyvratt, Matthew J.,Nargund, Ravi P.
scheme or table, p. 2074 - 2077 (2010/07/03)
This Letter describes a series of potent and selective BRS-3 agonists containing a biarylethylimidazole pharmacophore. Extensive SAR studies were carried out with different aryl substitutions. This work led to the identification of a compound 2-{2-[4-(pyridin-2-yl)phenyl]ethyl}-5-(2,2-dimethylbutyl)-1H-imidazole 9 with excellent binding affinity (IC50 = 18 nM, hBRS-3) and functional agonist activity (EC50 = 47 nM, 99% activation). After oral administration, compound 9 had sufficient exposure in diet induced obese mice to demonstrate efficacy in lowering food intake and body weight via BRS-3 activation.
