1.
Bioorg Med Chem Lett
; 22(2): 901-6, 2012 Jan 15.
Article
in English
| MEDLINE
| ID: mdl-22209458
ABSTRACT
We describe here our attempts to optimise the human fatty acid amide hydrolase (FAAH) inhibition and physicochemical properties of our previously reported tetrasubstituted azetidine urea FAAH inhibitor, VER-156084. We describe the SAR of a series of analogues and conclude with the demonstration of in vivo dose-dependant FAAH inhibition in an anandamide-loading study in rats.
Subject(s)
Amidohydrolases/antagonists & inhibitors , Azetidines/pharmacology , Enzyme Inhibitors/pharmacology , Urea/pharmacology , Amidohydrolases/metabolism , Animals , Azetidines/chemical synthesis , Azetidines/chemistry , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/metabolism , Dose-Response Relationship, Drug , ERG1 Potassium Channel , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Ether-A-Go-Go Potassium Channels/antagonists & inhibitors , Humans , Models, Molecular , Molecular Structure , Rats , Stereoisomerism , Structure-Activity Relationship , Urea/chemical synthesis , Urea/chemistry
2.
Bioorg Med Chem Lett
; 19(15): 4241-4, 2009 Aug 01.
Article
in English
| MEDLINE
| ID: mdl-19515560
ABSTRACT
We report the discovery of a novel, chiral azetidine urea inhibitor of Fatty Acid Amide Hydrolase (FAAH,) and describe the surprising species selectivity of VER-156084 versus rat and human FAAH and also hCB1.
