Synthesis of Novel Benzo-Fused Heteroaryl Derivatives as Ca2+/Calmodulin-Dependent Protein Kinase II Inhibitors

Autor:	Shogo Nakatani, Shigehiro Asano, Erina Koga, Yoshiaki Isobe, Nobuyuki Koike, Masafumi Komiya, Junetsu Igarashi
Rok vydání:	2013
Předmět:	Chemistry Stereochemistry General Chemistry General Medicine Mitogen-activated protein kinase kinase MAP2K7 chemistry.chemical_compound Benzothiazole Ca2+/calmodulin-dependent protein kinase Drug Discovery cardiovascular system Cyclin-dependent kinase 9 c-Raf Benzofuran Protein kinase A
Zdroj:	Chemical and Pharmaceutical Bulletin. 61:1094-1097
ISSN:	1347-5223 0009-2363
Popis:	Based on the structure activity relationship of 2-(4-phenoxybenzoyl)-5-hydroxyindole (1), a novel structural class of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitors were synthesized. We show in this study that the acidic proton at the N(1)-position of the indole moiety is not essential for CaMKII inhibitory activity. Among the synthesized compounds, we found the benzofuran and benzothiazole derivative as promising scaffolds for the developement of potent CaMKII inhibitors. In particular, compounds 8 and 14 inhibited CaMKII with IC₅₀ values of 24 nM and 32 nM, respectively.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::f8befc4d4bb879d1166cae57d59d762f https://doi.org/10.1248/cpb.c13-00493 Zobrazit plný text záznamu