title: Novel antidiabetic and hypolipidemic agents. 3. Benzofuran-containing thiazolidinediones.
abstract: Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2, 2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6, 7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2- ylmethoxy]pheny lene]thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.
authors.affiliation: Medicinal and Organic Chemistry, Dr. Reddy's Research Foundation, Bollaram Road, Miyapur, Hyderabad 500 050, India.
authors.forename: K A
authors.initials: KA
authors.lastname: Reddy
authors.forename: B B
authors.initials: BB
authors.lastname: Lohray
authors.forename: V
authors.initials: V
authors.lastname: Bhushan
authors.forename: A C
authors.initials: AC
authors.lastname: Bajji
authors.forename: K V
authors.initials: KV
authors.lastname: Reddy
authors.forename: P R
authors.initials: PR
authors.lastname: Reddy
authors.forename: T H
authors.initials: TH
authors.lastname: Krishna
authors.forename: I N
authors.initials: IN
authors.lastname: Rao
authors.forename: H K
authors.initials: HK
authors.lastname: Jajoo
authors.forename: N V
authors.initials: NV
authors.lastname: Rao
authors.forename: R
authors.initials: R
authors.lastname: Chakrabarti
authors.forename: T
authors.initials: T
authors.lastname: Dileepkumar
authors.forename: R
authors.initials: R
authors.lastname: Rajagopalan
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists; D014280:Triglycerides / Q000097:blood
chemical_list: C119475:5-(4-(N-(5-benzyloxy-2,3-dihydro-2,2,4,6,7-pentamethylbenzofuran-3-ylmethyl)pyrrolidin-2-ylmethoxy)phenylene)thiazolidine-2,4-dione; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D011759:Pyrrolidines; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D014157:Transcription Factors; D014280:Triglycerides