title: Substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones as hypoglycemic agents.
abstract: A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies.
authors.affiliation: Metabolic & Cardiovascular Diseases Research, Novartis Institute for Biomedical Research, 556 Morris Avenue, Summit, New Jersey 07901, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Aicher
authors.forename: B
authors.initials: B
authors.lastname: Balkan
authors.forename: P A
authors.initials: PA
authors.lastname: Bell
authors.forename: L J
authors.initials: LJ
authors.lastname: Brand
authors.forename: S H
authors.initials: SH
authors.lastname: Cheon
authors.forename: R O
authors.initials: RO
authors.lastname: Deems
authors.forename: J B
authors.initials: JB
authors.lastname: Fell
authors.forename: W S
authors.initials: WS
authors.lastname: Fillers
authors.forename: J D
authors.initials: JD
authors.lastname: Fraser
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: D C
authors.initials: DC
authors.lastname: Knorr
authors.forename: G G
authors.initials: GG
authors.lastname: Kahle
authors.forename: C L
authors.initials: CL
authors.lastname: Leone
authors.forename: J
authors.initials: J
authors.lastname: Nadelson
authors.forename: R
authors.initials: R
authors.lastname: Simpson
authors.forename: H C
authors.initials: HC
authors.lastname: Smith
mesh_terms: D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000166:cytology; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D010080:Oxazoles; D011758:Pyrroles; C115586:SDZ PGU 693; D013844:Thiazoles; D005947:Glucose