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  • Title: Novel euglycemic and hypolipidemic agents. 1.
    Author: Lohray BB, Bhushan V, Rao BP, Madhavan GR, Murali N, Rao KN, Reddy AK, Rajesh BM, Reddy PG, Chakrabarti R, Vikramadithyan RK, Rajagopalan R, Mamidi RN, Jajoo HK, Subramaniam S.
    Journal: J Med Chem; 1998 May 07; 41(10):1619-30. PubMed ID: 9572887.
    Abstract:
    A series of [[(heterocyclyl)ethoxy]benzyl]-2,4-thiazolidinediones have been synthesized by the condensation of corresponding aldehyde 1 and 2,4-thiazolidinedione followed by hydrogenation. Both unsaturated thiazolidinedione 2 and its saturated counterpart 3 have shown antihyperglycemic activity. Many of these compounds have shown superior euglycemic and hypolipidemic activity compared to troglitazone (CS 045). The indole analogue DRF-2189 (3g) was found to be a very potent insulin sensitizer, comparable to BRL-49653 in genetically obese C57BL/6J-ob/ob and 57BL/KsJ-db/db mice. Pharmacokinetic and tissue distribution studies conducted on BRL-49653 and DRF-2189 (3g) indicate that these drugs are well-distributed in target tissues. On the basis of euglycemic activity as well as enhanced selectivity against reduction of triglycerides in plasma, DRF-2189 (3g) has been selected for further evaluation.
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