Studies on antidiabetic agents. Synthesis and hypoglycemic activity of 5-[4-(pyridylalkoxy)benzyl]-2,4-thiazolidinediones.
The synthesis of a series of 5-[4-(pyridylalkoxy)benzyl]-2, 4-thiazolidinediones is described. These compounds were evaluated for hypoglycemic and hypolipidemic activities in genetically obese and diabetic mice, yellow KK. 2-(2-Pyridyl)alkoxy derivatives were found to have much better hypoglycemic and hypolipidemic activities than 2-(3-pyridyl)- and 2-(4-pyridyl)alkoxy derivatives or even the previously reported compound, ciglitazone. The introduction of a hydroxyl group at the 2-position of the ethoxy chain potentiated the activities. Among the potent compounds, pioglitazone (AD-4833) was selected as a candidate compound.
Sohda
T
T
Central Research Division, Takeda Chemical Industries, Ltd. Osaka, Japan.
Momose
Y
Y
Meguro
K
K
Kawamatsu
Y
Y
Sugiyama
Y
Y
Ikeda
H
H
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D007004:Hypoglycemic Agents / Q000138:chemical synthesis*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D000077205:Pioglitazone; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood
D007004:Hypoglycemic Agents; D011725:Pyridines; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; C039671:ciglitazone; D000077205:Pioglitazone