51071-50-2Relevant academic research and scientific papers
Divergent 2-Chloroquinazolin-4(3H)-one Rearrangement: Twisted-Cyclic Guanidine Formation or Ring-Fused N-Acylguanidines via a Domino Process
Yan, Gang,Zekarias, Bereket L.,Li, Xiaoyu,Jaffett, Victor A.,Guzei, Ilia A.,Golden, Jennifer E.
supporting information, p. 2486 - 2492 (2020/02/13)
A highly efficient 2-chloroquinazolin-4(3H)-one rearrangement was developed that predictably generates either twisted-cyclic or ring-fused guanidines in a single operation, depending on the presence of a primary versus secondary amine in the accompanying diamine reagent. Exclusive formation of twisted-cyclic guanidines results from pairing 2-chloroquinazolinones with secondary diamines. Use of primary amine-containing diamines permits a domino quinazolinone rearrangement/intramolecular cyclization, gated through (E)-twisted-cyclic guanidines, to afford ring-fused N-acylguanidines. This scalable, structurally tolerant transformation generated 55 guanidines and delivered twisted-cyclic guanidines with robust plasma stability and an abbreviated total synthesis of an antitumor ring-fused guanidine (4 steps, 55 % yield).
Fragment-based Discovery of a Small-Molecule Protein Kinase C-iota Inhibitor Binding Post-kinase Domain Residues
Kwiatkowski, Jacek,Baburajendran, Nithya,Poulsen, Anders,Liu, Boping,Tee, Doris Hui Ying,Wong, Yun Xuan,Poh, Zhi Ying,Ong, Esther H.Q.,Dinie, Nurul,Cherian, Joseph,Jansson, Anna Elisabet,Hill, Jeffrey,Keller, Thomas H.,Hung, Alvin W.
supporting information, p. 318 - 323 (2019/03/19)
The atypical protein kinase C-iota (PKC-l) enzyme is implicated in various cancers and has been put forward as an attractive target for developing anticancer therapy. A high concentration biochemical screen identified pyridine fragment weakly inhibiting PKC-l with IC50 = 424 μM. Driven by structure-activity relationships and guided by docking hypothesis, the weakly bound fragment was eventually optimized into a potent inhibitor of PKC-l (IC50= 270 nM). Through the course of the optimization, an intermediate compound was crystallized with the protein, and careful analysis of the X-ray crystal structure revealed a unique binding mode involving the post-kinase domain (C-terminal tail) of PKC-l.
