54093-14-0Relevant academic research and scientific papers
Pyrimidine-Based Inhibitors of Dynamin I GTPase Activity: Competitive Inhibition at the Pleckstrin Homology Domain
Odell, Luke R.,Abdel-Hamid, Mohammed K.,Hill, Timothy A.,Chau, Ngoc,Young, Kelly A.,Deane, Fiona M.,Sakoff, Jennette A.,Andersson, Sofia,Daniel, James A.,Robinson, Phillip J.,McCluskey, Adam
supporting information, p. 349 - 361 (2017/04/26)
The large GTPase dynamin mediates membrane fission during clathrin-mediated endocytosis (CME). The aminopyrimidine compounds were reported to disrupt dynamin localization to the plasma membrane via the PH domain and implicate this mechanism in the inhibition of CME. We have used a computational approach of binding site identification, docking, and interaction energy calculations to design and synthesize a new library of aminopyrimidine analogues targeting site-2 of the pleckstrin homology (PH) domain. The optimized analogues showed low micromolar inhibition against both dynamin I (IC50 = 10.6 ± 1.3 to 1.6 ± 0.3 μM) and CME (IC50(CME) = 65.9 ± 7.7 to 3.7 ± 1.1 mM), which makes this series among the more potent inhibitors of dynamin and CME yet reported. In CME and growth inhibition cell-based assays, the data obtained was consistent with dynamin inhibition. CEREP ExpresS profiling identified off-target effects at the cholecystokinin, dopamine D2, histamine H1 and H2, melanocortin, melatonin, muscarinic M1 and M3, neurokinin, opioid KOP and serotonin receptors.
Effect of halogen atom localization on the level of antimycobacterial activity of 2-amino-4-arylamino-6-methylpyrimidines
Erkin,Krutikov
experimental part, p. 818 - 824 (2011/01/07)
Several hydrochlorides of 2-alkyl(cycloalkyl, aralkyl)-5-bromo-6-methyl-4- phenylaminopyrimidines have been synthesized as isosteric analogs of the corresponding 2-alkyl(cycloalkyl, aralkyl)-4-(3-bromophenyl)amino-6- methylpyrimidine hydrochlorides. Moving the bromine atom from the benzene ring into the heterocycle is accompanied by a significant decrease in the level of antimycobacterial activity. Pleiades Publishing, Ltd., 2010.
Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels
Hougaard,Eriksen,Jorgensen,Johansen,Dyhring,Madsen,Strobaek,Christophersen
, p. 655 - 665 (2008/03/12)
Background and purpose: Positive modulators of small conductance Ca 2+-activated K+ channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non-excitable cells. The prototype compound 1
Identification of aminopyrimidine regioisomers via line broadening effects in1H and13C NMR spectroscopy
Garner, James,Hill, Tim,Odell, Luke,Keller, Paul,Morgan, Jody,McCluskey, Adam
, p. 1079 - 1083 (2007/10/03)
Substituted mono- and diamino-pyrimidines were synthesized as part of our medicinal chemistry programmes. Primary amines substituted at the 4-position exhibited room-temperature line broadening effects in both 1H and 13C NMR spectros
