Discovery of N-Ethyl-4-[2-(4-fluoro-2,6-dimethyl-phenoxy)-5-(1-hydroxy-1-methyl-ethyl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide (ABBV-744), a BET Bromodomain Inhibitor with Selectivity for the Second Bromodomain was written by Sheppard, George S.;Wang, Le;Fidanze, Steven D.;Hasvold, Lisa A.;Liu, Dachun;Pratt, John K.;Park, Chang H.;Longenecker, Kenton;Qiu, Wei;Torrent, Maricel;Kovar, Peter J.;Bui, Mai;Faivre, Emily;Huang, Xiaoli;Lin, Xiaoyu;Wilcox, Denise;Zhang, Lu;Shen, Yu;Albert, Daniel H.;Magoc, Terrance J.;Rajaraman, Ganesh;Kati, Warren M.;McDaniel, Keith F.. And the article was included in Journal of Medicinal Chemistry in 2020.COA of Formula: C9H11Br This article mentions the following:
The BET family of proteins consists of BRD2, BRD3, BRD4, and BRDt. Each protein contains two distinct bromodomains (BD1 and BD2). BET family bromodomain inhibitors under clin. development for oncol. bind to each of the eight bromodomains with similar affinities. We hypothesized that it may be possible to achieve an improved therapeutic index by selectively targeting subsets of the BET bromodomains. Both BD1 and BD2 are highly conserved across family members (>70% identity), whereas BD1 and BD2 from the same protein exhibit a larger degree of divergence (~40% identity), suggesting selectivity between BD1 and BD2 of all family members would be more straightforward to achieve. Exploiting the Asp144/His437 and Ile146/Val439 sequence differences (BRD4 BD1/BD2 numbering) allowed the identification of compound 27 demonstrating greater than 100-fold selectivity for BRD4 BD2 over BRD4 BD1. Further optimization to improve BD2 selectivity and oral bioavailability resulted in the clin. development compound 46 (ABBV-744). In the experiment, the researchers used many compounds, for example, 2-(Bromomethyl)-1,3-dimethylbenzene (cas: 83902-02-7COA of Formula: C9H11Br).
2-(Bromomethyl)-1,3-dimethylbenzene (cas: 83902-02-7) belongs to organobromine compounds. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.COA of Formula: C9H11Br
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary