Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists was written by Shi, Jun;Gu, Zhengxiang;Jurica, Elizabeth Anne;Wu, Ximao;Haque, Lauren E.;Williams, Kristin N.;Hernandez, Andres S.;Hong, Zhenqiu;Gao, Qi;Dabros, Marta;Davulcu, Akin H.;Mathur, Arvind;Rampulla, Richard A.;Gupta, Arun Kumar;Jayaram, Ramya;Apedo, Atsu;Moore, Douglas B.;Liu, Heng;Kunselman, Lori K.;Brady, Edward J.;Wilkes, Jason J.;Zinker, Bradley A.;Cai, Hong;Shu, Yue-Zhong;Sun, Qin;Dierks, Elizabeth A.;Foster, Kimberly A.;Xu, Carrie;Wang, Tao;Panemangalore, Reshma;Cvijic, Mary Ellen;Xie, Chunshan;Cao, Gary G.;Zhou, Min;Krupinski, John;Whaley, Jean M.;Robl, Jeffrey A.;Ewing, William R.;Ellsworth, Bruce Alan. And the article was included in Journal of Medicinal Chemistry in 2018.Electric Literature of C7H6BrF This article mentions the following:
G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clin. to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound I), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound I demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models. In the experiment, the researchers used many compounds, for example, 3-Bromo-4-fluorotoluene (cas: 452-62-0Electric Literature of C7H6BrF).
3-Bromo-4-fluorotoluene (cas: 452-62-0) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Electric Literature of C7H6BrF
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary