Novel Euglycemic and Hypolipidemic Agents. 1

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. Man...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1998-05, Vol.41 (10), p.1619-1630
Main Authors: Lohray, Braj B, Bhushan, Vidya, Rao, Bheema P, Madhavan, Gurram R, Murali, Nagabelli, Rao, Krovvidi N, Reddy, Ananth K, Rajesh, Bagepalli M, Reddy, Pamulapati G, Chakrabarti, Ranjan, Vikramadithyan, Reeba K, Rajagopalan, Ramanujam, Mamidi, Rao N. V. S, Jajoo, Hemant K, Subramaniam, Swaminathan
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blood Glucose - metabolism
Drug Evaluation, Preclinical
General and cellular metabolism. Vitamins
Hypoglycemic Agents - chemical synthesis
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - pharmacology
Hypolipidemic Agents - chemical synthesis
Hypolipidemic Agents - chemistry
Hypolipidemic Agents - pharmacokinetics
Hypolipidemic Agents - pharmacology
Indoles - chemical synthesis
Indoles - chemistry
Indoles - pharmacokinetics
Indoles - pharmacology
Male
Medical sciences
Mice
Mice, Inbred C57BL
Pharmacology. Drug treatments
Rats
Rats, Wistar
Structure-Activity Relationship
Thiazoles - chemical synthesis
Thiazoles - chemistry
Thiazoles - pharmacokinetics
Thiazoles - pharmacology
Thiazolidinediones
Tissue Distribution
Triglycerides - blood
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm970444e