4,5-dialkylsubstituted 2-imino-1,3-thiazolidine derivatives as potent inducible nitric oxide synthase inhibitors

Bioorganic & Medicinal Chemistry
Shigeo UedaMotoji Kawasaki

Abstract

In the course of our search for selective iNOS inhibitors, we have previously reported that 2-imino-1,3-oxazolidine derivatives (1) and 2-aminothiazole derivatives (2) are selective iNOS inhibitors. In order to find more potent iNOS inhibitors, we focused our efforts on the synthesis and evaluation of the inhibitory activity against iNOS and selectivity for iNOS both in vitro and in vivo of a series of 2-imino-1,3-thiazolidine derivatives (3), which are analogues of 1 and 2. Our results show that among the compounds synthesized (4R,5R)-5-ethyl-2-imino-4-methyl-1,3-thiazolidine [(4R,5R)-14a: ES-1537] exhibited potent inhibitory activity and selectivity for iNOS. In addition, ES-1537 had good pharmacokinetic profile in rats with BA value of 80%. It is therefore expected that ES-1537 may be therapeutically useful for the treatment of diseases related to excess production of NO.

Citations

Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Ying-Qi Li
Sep 14, 2007·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dinesh Ramesh GarudHideharu Ishihara
Oct 13, 2016·The Journal of Organic Chemistry·Mani SengodenTharmalingam Punniyamurthy
Sep 11, 2019·Medicinal Research Reviews·Richa MinhasGulshan Bansal
Mar 25, 2020·Topics in Current Chemistry·Nusrat SahibaShikha Agarwal

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