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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Glucose / metabolism
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Drug Evaluation, Preclinical
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Hypoglycemic Agents* / chemical synthesis
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Hypoglycemic Agents* / chemistry
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Hypoglycemic Agents* / pharmacokinetics
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Hypoglycemic Agents* / pharmacology
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Hypolipidemic Agents* / chemical synthesis
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Hypolipidemic Agents* / chemistry
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Hypolipidemic Agents* / pharmacokinetics
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Hypolipidemic Agents* / pharmacology
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Indoles* / chemical synthesis
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Indoles* / chemistry
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Indoles* / pharmacokinetics
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Indoles* / pharmacology
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Male
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Mice
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Mice, Inbred C57BL
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Rats
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Rats, Wistar
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Rosiglitazone
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Structure-Activity Relationship
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Thiazoles* / chemical synthesis
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Thiazoles* / chemistry
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Thiazoles* / pharmacokinetics
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Thiazoles* / pharmacology
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Thiazolidinediones*
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Tissue Distribution
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Triglycerides / blood
Substances
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5-((4-(2-(1-indolyl)ethoxy)-phenyl)methyl)thiazolidine-2,4-dione
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Blood Glucose
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Hypoglycemic Agents
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Hypolipidemic Agents
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Indoles
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Thiazoles
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Thiazolidinediones
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Triglycerides
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Rosiglitazone