Abstract
In our continued effort to discover novel PTP1B inhibitor with improved in vivo activity we attempeted to optimize our previously discoved lead compound by replacing the sulfonyl group with benzoyl group to yield compound II. Additional structural modifications were performed on compound II to yield a series of 24 aryl phenylthiazolyl phenylcarboxamides as potential PTP1B inhibitors. Among these compounds six compounds showed good PTP1B inhibitory activity in the order of compound 38 > 30 > 29 > 37 > 22 > 19. The plausible PTP1B binding site interaction of compound 38 showed favorable binding similar to known PTP1B binders and suggest its selectivity towards PTP1B. Compound 38 also showed promising antihyperglycemic, antidyslipidemic and insulin resistant reversal activities in vivo in STZ model and db/db mice model. Altogether, the compound 38 present an excellent candidate for future PTP1B targeted drug discovery.