Antihyperglycemic activity of novel naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides.
A series of naphthalenyl 3H-1,2,3,5-oxathiadiazole 2-oxides was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. Substitution at the 1-, 5-, or 8-positions of the naphthalene ring with a halogen was found to be beneficial to antihyperglycemic activity. 4-[(5-Chloronaphthalen-2-yl)methyl]-3H-1,2,3,5-oxathiadiazole++ + 2-oxide (45), one of the most potent compounds in this series, was selected for further pharmacological evaluation.
Ellingboe
J W
JW
Division of Exploratory Chemistry, Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
Lombardo
L J
LJ
Alessi
T R
TR
Nguyen
T T
TT
Guzzo
F
F
Guinosso
C J
CJ
Bullington
J
J
Browne
E N
EN
Bagli
J F
JF
Wrenn
J
J
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D005260:Female; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009281:Naphthalenes; D013830:Thiadiazoles; C082817:WAY 120744