title: 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.
abstract: 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.
authors: Roche Research Center, Hoffmann-LaRoche Inc., Nutley, NJ 07110, USA. kevin.guertin@roche.com
authors: Kevin R
authors: KR
authors: Guertin
authors: Lina
authors: L
authors: Setti
authors: Lida
authors: L
authors: Qi
authors: Rachel M
authors: RM
authors: Dunsdon
authors: Brian W
authors: BW
authors: Dymock
authors: Philip S
authors: PS
authors: Jones
authors: Hilary
authors: H
authors: Overton
authors: Mathew
authors: M
authors: Taylor
authors: Glyn
authors: G
authors: Williams
authors: Joseph A
authors: JA
authors: Sergi
authors: Karen
authors: K
authors: Wang
authors: Ying
authors: Y
authors: Peng
authors: Marcia
authors: M
authors: Renzetti
authors: Rogely
authors: R
authors: Boyce
authors: Fiorenza
authors: F
authors: Falcioni
authors: Ralph
authors: R
authors: Garippa
authors: Andrée R
authors: AR
authors: Olivier
mesh_terms: 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*
chemical_list: D001786:Blood Glucose; D003959:Diamines; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D014227:Triazines; D017027:Protein Tyrosine Phosphatases; D004229:Dithiothreitol