Synthesis of indole-ring fluorine-labeled analogs of LY333531, an isoform-selective inhibitor of protein kinase C

Autor:	Peter G. Goekjian, Lawrence M. Ballas, Michael R. Jirousek, James W. White, Dale J. Thompson, John O. Cole, Jeffrey T. Dixon, Tamara P. Dudley, Priscilla Lugo-Mas, Stacy L. Cable
Rok vydání:	1999
Předmět:	Gene isoform Indole test Stereochemistry Organic Chemistry chemistry.chemical_element Ring (chemistry) Biochemistry Catalysis Inorganic Chemistry chemistry.chemical_compound chemistry Fluorine Environmental Chemistry Physical and Theoretical Chemistry Protein kinase A Maleimide Protein kinase C
Zdroj:	Journal of Fluorine Chemistry. 98:137-142
ISSN:	0022-1139
Popis:	Two fluorine-labeled analogs of LY333531, a potent, ATP-competitive, and isoform-selective inhibitor of protein kinase C-beta, have been prepared. 19 F-NMR labels were placed on the indole rings to probe for differences in the catalytic domains of the PKC isoforms. The fluorinated bis(indolyl)maleimide was prepared by a Steglich coupling of 5-fluoroindole with N-methyl dichloromaleimide, and was coupled to a chiral, aliphatic dimesylate prepared from 1(S)-[(2R)-1,4-dioxaspiro[4.5]decanyl]3-buten-1-ol. The coupling-macrocyclization step was performed by slow addition of a mixture of the bis(indolyl)maleimide and the dimesylate to a suspension of cesium carbonate in DMF, and adjustment of the functionality provided the final labeled analog 1. A simplified analog 2 was prepared from diiodohexane by a similar procedure. Compounds 1 and 2 had IC(50)'s of 5 and 6 nM, respectively, against PKC-beta(II), and of 57 and 79 nM, respectively, against PKC-alpha.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6c1f94649270de64009b307bb122a302 https://doi.org/10.1016/s0022-1139(99)00095-0 Zobrazit plný text záznamu Full Text from ScienceDirect