Identification of a novel class of orally active pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-based hypoglycemic agents with protein tyrosine phosphatase inhibitory activity.
A novel series of orally active pyrimido[5,4-3][1,2,4]triazine-5,7-diamine-based hypoglycemic agents have been identified. These compounds show non-selective inhibitory properties against a panel of protein tyrosine phosphatases including PTP1B. Compounds 12 and 13 display oral glucose lowering effects in ob/ob mice.
Guertin
Kevin R
KR
Roche Research Center, Hoffmann-LaRoche Inc., Nutley, NJ 07110, USA. kevin.guertin@roche.com
Setti
Lina
L
Qi
Lida
L
Dunsdon
Rachel M
RM
Dymock
Brian W
BW
Jones
Philip S
PS
Overton
Hilary
H
Taylor
Mathew
M
Williams
Glyn
G
Sergi
Joseph A
JA
Wang
Karen
K
Peng
Ying
Y
Renzetti
Marcia
M
Boyce
Rogely
R
Falcioni
Fiorenza
F
Garippa
Ralph
R
Olivier
Andrée R
AR
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects; D003959:Diamines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004229:Dithiothreitol / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D003959:Diamines; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D014227:Triazines; D017027:Protein Tyrosine Phosphatases; D004229:Dithiothreitol