Novel benzoxazole 2,4-thiazolidinediones as potent hypoglycemic agents. Synthesis and structure-activity relationships.
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.
Arakawa
K
K
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Inamasu
M
M
Matsumoto
M
M
Okumura
K
K
Yasuda
K
K
Akatsuka
H
H
Kawanami
S
S
Watanabe
A
A
Homma
K
K
Saiga
Y
Y
Ozeki
M
M
Iijima
I
I
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
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