1.
Bioorg Med Chem Lett
; 18(9): 2799-804, 2008 May 01.
Article
in English
| MEDLINE
| ID: mdl-18434143
ABSTRACT
3-Aryl-5-phenyl-(1,2,4)-triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). They are active in both in vitro and an in vivo mouse pharmacodynamic (PD) model. The synthesis and structure activity relationships are presented.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , Enzyme Inhibitors , Hydrocarbons, Aromatic , Hypoglycemic Agents , Metabolic Syndrome/drug therapy , Triazoles , Animals , Binding Sites , Disease Models, Animal , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacokinetics , Enzyme Inhibitors/therapeutic use , Hydrocarbons, Aromatic/chemical synthesis , Hydrocarbons, Aromatic/pharmacology , Hydrocarbons, Aromatic/therapeutic use , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/therapeutic use , Inhibitory Concentration 50 , Mice , Models, Chemical , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/pharmacology , Triazoles/therapeutic use
2.
Bioorg Med Chem Lett
; 17(24): 6723-8, 2007 Dec 15.
Article
in English
| MEDLINE
| ID: mdl-18029181
ABSTRACT
A urea class of high affinity niacin receptor agonists was discovered. Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin.
