Amination/Cyclization Cascade by Acid-Catalyzed Activation of Indolenine for the One-Pot Synthesis of Phaitanthrin E
We have developed a concise one-pot synthesis of phaitanthrin E derivatives, where simple starting materials undergo an acid-catalyzed intermolecular amination/intramolecular cyclization cascade.
1,3,4-Oxadiazole-2(3H)-thione Analogs as PIM Kinase Inhibitors
Proviral integration site for moloney murine leukemia virus (PIM) kinases are highly expressed in hematological cancers. They phosphorylate downstream substrates that contribute to tumor growth and survival. Therefore, a potent inhibitor of PIM kinases is expected to be effective at treating hematological cancers. In the present study, several indole derivatives of 1,3,4-oxadiazole-2(3H)-thione were synthesized and evaluated as PIM kinase inhibitors. Structure–activity relationship studies yielded potent inhibitors of all three PIM kinases in the single-digit to low double-digit nanomolar IC50 range. Kinase profiling of a representative compound showed high selectivity among 15 other kinases.
Choo, Hyeonseong,Hong, Victor Sukbong,Jeong, Seungik,Lee, Jinho,Won, Jongin,Yun, Yanghwan
p. 994 - 1001
(2020/10/02)
Identification of azepinone fused tetracyclic heterocycles as new chemotypes with protein kinase inhibitory activities
The design and synthesis of small tetracyclic heterocycles which bear two new regioisomeric 2-carboxyethyl-1H-pyrrole-annulated indoloazepinone scaffolds is described. An azepinone motif, which is inherent in the structures of many well studied protein kinase inhibitors, serves as prominent structural feature of the new compounds. Concise access to the new regioisomeric tetracyclic derivatives was accomplished through amide coupling of appropriate pyrrole and indole precursors followed by an intramolecular Heck coupling reaction of the intermediate amide conjugates. Preliminary evaluation of newly synthesized tetracyclic molecules against a panel of protein kinases indicated their inhibitory activities and revealed promising selectivity profiles. The new compounds displayed no significant antiproliferative activity against MCF-7 cancer cells. Interestingly, derivative 19a exhibited selective TAK1 kinase inhibitory activity and figures as a promising chemotype for the discovery of new TAK1 inhibitors.
Psarra, Vassiliki,Fousteris, Manolis A.,Hennig, Lothar,Bantzi, Marina,Giannis, Athanassios,Nikolaropoulos, Sotiris S.
supporting information
p. 2376 - 2385
(2016/04/26)
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