Exploration of Novel 2-Alkylimino-1,3-thiazolines: T-Type Calcium Channel Inhibitory Activity

Title
Exploration of Novel 2-Alkylimino-1,3-thiazolines: T-Type Calcium Channel Inhibitory Activity
Authors
한민수남기달신동윤정낙철한호규
Keywords
thiazolines; T-Type; Calcium channel; Combinatorial chemistry; neuropathic pain
Issue Date
2010-07
Publisher
Journal of combinatorial chemistry
Citation
VOL 12, NO 4, 518-530
Abstract
We have developed combinatorial libraries of new 2-alkylimino-1,3-thiazolines with four diversity points, consisting of more than 500 compounds, in a parallel synthetic fashion. The synthetic strategy was based on the construction of a large library aimed at the discovery of new compounds with T-type calcium channel inhibitory activity through structure modifications of hit compound 2. The syntheses of the compounds of Chemset A with four diversity points were accomplished by the condensation of thioureas 5 with α-haloketones 6{1-66} having two diversity points each. A library of phthalimidyl 1,3-thiazolines 24 was synthesized to provide Chemset B, which allowed the introduction of other diversity points through the nucleophilic character of the amino nitrogen. A sublibrary, Chemset C, was constructed from the libraries of Chemset A and Chemset B by functionalization of the C-4 position of the 1,3-thiazoline ring. The products containing ester or acid groups at the C-4 position of the 1,3- thiazoline ring were used in amide synthesis to give a new sublibrary within Chemset C. Deprotection of the phthalimidyl moiety of 24 followed by the reaction with benzoyl chloride gave the corresponding sublibrary in Chemset C. Another sublibrary which includes secondary amino derivatives was obtained by reduction of the amide moiety or reductive amination of 23 with phenyl aldehyde. The selected compounds from the generated libraries were evaluated with respect to inhibition of T-type calcium channels, where some of them have exhibited promising activity.
URI
http://pubs.kist.re.kr/handle/201004/38371
ISSN
1520-4766
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KIST Publication > Article
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