18276-84-1Relevant academic research and scientific papers
Addressing the Glycine-Rich Loop of Protein Kinases by a Multi-Facetted Interaction Network: Inhibition of PKA and a PKB Mimic
Lauber, Birgit S.,Hardegger, Leo A.,Asraful, Alam K.,Lund, Bjarte A.,Dumele, Oliver,Harder, Michael,Kuhn, Bernd,Engh, Richard A.,Diederich, Fran?ois
, p. 211 - 221 (2016)
Protein kinases continue to be hot targets in drug discovery research, as they are involved in many essential cellular processes and their deregulation can lead to a variety of diseases. A series of 32 enantiomerically pure inhibitors was synthesized and tested towards protein kinase A (PKA) and protein kinase B mimic PKAB3 (PKA triple mutant). The ligands bind to the hinge region, ribose pocket, and glycine-rich loop at the ATP site. Biological assays showed high potency against PKA, with Ki values in the low nanomolar range. The investigation demonstrates the significance of targeting the often neglected glycine-rich loop for gaining high binding potency. X-ray co-crystal structures revealed a multi-facetted network of ligand-loop interactions for the tightest binders, involving orthogonal dipolar contacts, sulfur and other dispersive contacts, amide-π stacking, and H-bonding to organofluorine, besides efficient water replacement. The network was analyzed in a computational approach.
Mukaiyama reagent-promoted metal-free preparation of alkynyl sulfones and phosphonates under mild conditions
Qi, Danyang,Dong, Wanrong,Peng, Zhihong,Zhang, Yingjun,An
, (2019/08/01)
An efficient and mild route for the formation sulfur or phosphor-substituted alkynes was herein demonstrated. The Mukaiyama reagent-mediated transformation started from easily-accessible substrates without carbon-carbon triple bonds, and the reaction proceeded under mild conditions (room temperature) in a one-pot manner, requiring for no transition metal-catalysts. The practical protocol featured for good functional groups tolerance (up to 41 examples) and high efficiency (up to 91% yields) towards alkynyl sulfones and alkynyl phosphonates at low cost.
Base-induced one-pot preparation of N- or P-substituted alkynes
Zhang, Yang,Zhang, Yanqin,Xiao, Jing,Peng, Zhihong,Dong, Wanrong,An, Delie
supporting information, p. 7806 - 7815 (2015/12/31)
An efficient method for the formation of C(sp)-N or C(sp)-P bonds is described. The facile transformation proceeds under mild conditions (0 or -20 °C) in a one-pot manner, and does not require transition-metal catalysts. The base-induced protocol exhibits good functional group tolerance (up to 44 examples) and high efficiency (up to 94 % yield) towards rare heteroatom-substituted acetylenes (N or P). Furthermore, the proposed mechanism was supported by the isolation of a key intermediate. An efficient method for the formation of C(sp)-N or C(sp)-P bonds is described. The facile transformation proceeds in the absence of any transition-metal catalysts under mild conditions (0 or -20 °C) in a one-pot manner with good functional group compatibility and with high efficiency.
