title: Novel benzoxazole 2,4-thiazolidinediones as potent hypoglycemic agents. Synthesis and structure-activity relationships.
abstract: A new series of benzoxazole 2,4-thiazolidinediones was synthesized and evaluated for hypoglycemic activity in genetically obese and diabetic yellow KK mice. 2-Arylmethyl- and 2-(heteroarylmethyl)benzoxazole derivatives showed far more potent activity than known 2,4-thiazolidinedione derivatives such as ciglitazone, troglitazone and pioglitazone. A facile synthesis of benzoxazole 2,4-thiazolidinediones was also established using aminophenol 2,4-thiazolidinedione (11) as a key intermediate. Details of synthesis and structure-activity relationships for this series are described.
authors.affiliation: Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Arakawa
authors.forename: M
authors.initials: M
authors.lastname: Inamasu
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: K
authors.initials: K
authors.lastname: Yasuda
authors.forename: H
authors.initials: H
authors.lastname: Akatsuka
authors.forename: S
authors.initials: S
authors.lastname: Kawanami
authors.forename: A
authors.initials: A
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Homma
authors.forename: Y
authors.initials: Y
authors.lastname: Saiga
authors.forename: M
authors.initials: M
authors.lastname: Ozeki
authors.forename: I
authors.initials: I
authors.lastname: Iijima
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009765:Obesity; D000077205:Pioglitazone; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
chemical_list: D001578:Benzopyrans; D001583:Benzoxazoles; D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C089946:2,4-thiazolidinedione; D000077288:Troglitazone; C039671:ciglitazone; D000077205:Pioglitazone; C066021:englitazone