Structure-Based Drug Design of Bisubstrate Inhibitors of Phenylethanolamine N-Methyltransferase Possessing Low Nanomolar Affinity at Both Substrate Binding Domains1 was written by Lu, Jian;Bart, Aaron G.;Wu, Qian;Criscione, Kevin R.;McLeish, Michael J.;Scott, Emily E.;Grunewald, Gary L.. And the article was included in Journal of Medicinal Chemistry in 2020.Reference of 954-81-4 This article mentions the following:
The enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) catalyzes the final step in the biosynthesis of epinephrine and is a potential drug target, primarily for the control of hypertension. Unfortunately, many potent PNMT inhibitors also possess significant affinity for the a2-adrenoceptor, which complicates the interpretation of their pharmacol. A bisubstrate analog approach offers the potential for development of highly selective inhibitors of PNMT. This paper documents the design, synthesis, and evaluation of such analogs, several of which were found to possess human PNMT (hPNMT) inhibitory potency <5 nM vs. AdoMet. Site-directed mutagenesis studies were consistent with bisubstrate binding. Two of these compounds (19 and 29) were co-crystallized with hPNMT and the resulting structures revealed both compounds bound as predicted, simultaneously occupying both substrate binding domains. This bisubstrate inhibitor approach has resulted in one of the most potent (20) and selective (vs the a2-adrenoceptor) inhibitors of hPNMT yet reported. In the experiment, the researchers used many compounds, for example, N-(5-Bromopentyl)phthalimide (cas: 954-81-4Reference of 954-81-4).
N-(5-Bromopentyl)phthalimide (cas: 954-81-4) belongs to organobromine compounds. Organo bromine compounds are versatile compounds and are widely used in diverse fields. Organo bromine derivatives are used in the dye sector, as an indicator in analytical chemistry (Bromothymol blue is a popular indicator). The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.Reference of 954-81-4
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary