In 2014,Flanagan, Jack U.; Atwell, Graham J.; Heinrich, Daniel M.; Brooke, Darby G.; Silva, Shevan; Rigoreau, Laurent J. M.; Trivier, Elisabeth; Turnbull, Andrew P.; Raynham, Tony; Jamieson, Stephen M. F.; Denny, William A. published 《Morpholylureas as a new class of potent and selective inhibitors of the type 5 17-β-hydroxysteroid dehydrogenase (AKR1C3)》.Bioorganic & Medicinal Chemistry published the findings.Computed Properties of C5H3BrClN The information in the text is summarized as follows:
Inhibitors of the aldo-keto reductase enzyme AKR1C3 are of interest as potential drugs for leukemia and hormone-related cancers. A series of non-carboxylate morpholino(phenylpiperazin-1-yl)methanones were prepared by palladium-catalyzed coupling of substituted Ph or pyridyl bromides with the known morpholino(piperazin-1-yl)methanone, and shown to be potent (IC50 ∼ 100 nM) and very isoform-selective inhibitors of AKR1C3. Lipophilic electron-withdrawing substituents on the Ph ring were pos. for activity, as was an H-bond acceptor on the other terminal ring, and the ketone moiety (as a urea) was essential. These structure-activity relationships are consistent with an X-ray structure of a representative compound bound in the AKR1C3 active site, which showed H-bonding between the carbonyl oxygen of the drug and Tyr55 and His117 in the ‘oxyanion hole’ of the enzyme, with the piperazine bridging unit providing the correct twist to allow the terminal benzene ring to occupy the lipophilic pocket and align with Phe311.5-Bromo-2-chloropyridine(cas: 53939-30-3Computed Properties of C5H3BrClN) was used in this study.
5-Bromo-2-chloropyridine(cas: 53939-30-3) belongs to pyridine. When pyridine is adsorbed on oxide surfaces or in porous materials, the following species are commonly observed: (i) pyridine coordinated to Lewis acid sites, (ii) pyridine H-bonded to weakly acidic hydroxyls, and (iii) protonated pyridine. At high coverage, physisorbed pyridine and protonated dimers can also be observed.Computed Properties of C5H3BrClN