Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening was written by Wellaway, Christopher R.;Amans, Dominique;Bamborough, Paul;Barnett, Heather;Bit, Rino A.;Brown, Jack A.;Carlson, Neil R.;Chung, Chun-wa;Cooper, Anthony W. J.;Craggs, Peter D.;Davis, Robert P.;Dean, Tony W.;Evans, John P.;Gordon, Laurie;Harada, Isobel L.;Hirst, David J.;Humphreys, Philip G.;Jones, Katherine L.;Lewis, Antonia J.;Lindon, Matthew J.;Lugo, Dave;Mahmood, Mahnoor;McCleary, Scott;Medeiros, Patricia;Mitchell, Darren J.;O’Sullivan, Michael;Le Gall, Armelle;Patel, Vipulkumar K.;Patten, Chris;Poole, Darren L.;Shah, Rishi R.;Smith, Jane E.;Stafford, Kayleigh A. J.;Thomas, Pamela J.;Vimal, Mythily;Wall, Ian D.;Watson, Robert J.;Wellaway, Natalie;Yao, Gang;Prinjha, Rab K.. And the article was included in Journal of Medicinal Chemistry in 2020.Related Products of 144222-22-0 This article mentions the following:
The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET-KAc binding has emerged as an attractive therapeutic strategy with a number of small mol. inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochem., pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technol., with an N-Me pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose. In the experiment, the researchers used many compounds, for example, 1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0Related Products of 144222-22-0).
1-Boc-4-(Aminomethyl)piperidine (cas: 144222-22-0) belongs to piperidine derivatives. The piperidine ring can be found not only in more than half of the currently known structures of alkaloids, but also in many natural or synthetic compounds with interesting biological activities. The piperidine and polyhydroxylated indolizidine derivatives have shown to be promising 伪-glucosidase inhibitors. The former are analogs of DNJ with an improved 伪-glucosidase inhibitory profile than that of DNJ. Boisson et al.Related Products of 144222-22-0
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem