Antihyperglycemic activity of novel substituted 3H-1,2,3,5-oxathiadiazole 2-oxides.
A series of substituted 3H-1,2,3,5-oxathiadiazole-2-oxides (6) was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. The oxathiadiazoles 6 were synthesized by a two-step sequence: treatment of a substituted acetonitrile (4) with hydroxylamine to give the corresponding amidoxime (5) and cyclization with thionyl chloride to yield 6. In terms of potency, the 2-naphthalenylmethyl group (as in compound 3) was found to be the optimal substituent in this series. Compound 3 was approximately 5 times more potent than ciglitazone (1).
Ellinboe
J W
JW
Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
Alessi
T R
TR
Dolak
T M
TM
Nguyen
T T
TT
Tomer
J D
JD
Guzzo
F
F
Bagli
J F
JF
McCaleb
M L
ML
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D051381:Rats; D011924:Rats, Zucker; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D045162:Thiazolidinediones
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; C039671:ciglitazone