title: Novel euglycemic and hypolipidemic agents. 1.
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.
authors.affiliation: Medicinal and Organic Chemistry, Pharmacology, and Clinical Research, Dr. Reddy's Research Foundation, Bollaram Road, Miyapur Hyderabad 500 050, India.
authors.forename: B B
authors.initials: BB
authors.lastname: Lohray
authors.forename: V
authors.initials: V
authors.lastname: Bhushan
authors.forename: B P
authors.initials: BP
authors.lastname: Rao
authors.forename: G R
authors.initials: GR
authors.lastname: Madhavan
authors.forename: N
authors.initials: N
authors.lastname: Murali
authors.forename: K N
authors.initials: KN
authors.lastname: Rao
authors.forename: A K
authors.initials: AK
authors.lastname: Reddy
authors.forename: B M
authors.initials: BM
authors.lastname: Rajesh
authors.forename: P G
authors.initials: PG
authors.lastname: Reddy
authors.forename: R
authors.initials: R
authors.lastname: Chakrabarti
authors.forename: R K
authors.initials: RK
authors.lastname: Vikramadithyan
authors.forename: R
authors.initials: R
authors.lastname: Rajagopalan
authors.forename: R N
authors.initials: RN
authors.lastname: Mamidi
authors.forename: H K
authors.initials: HK
authors.lastname: Jajoo
authors.forename: S
authors.initials: S
authors.lastname: Subramaniam
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045162:Thiazolidinediones; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood
chemical_list: C112100:5-((4-(2-(1-indolyl)ethoxy)-phenyl)methyl)thiazolidine-2,4-dione; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007211:Indoles; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone