1.
Bioorg Med Chem Lett
; 17(7): 2031-5, 2007 Apr 01.
Article
in English
| MEDLINE
| ID: mdl-17270441
ABSTRACT
Optimization of the biological activity for 5,6-diarylpyridines as CB1 receptor inverse agonists is described. Food intake and pharmacokinetic evaluation of 3f and 15c indicate that these compounds are effective orally active modulators of CB1.
Subject(s)
Chemistry, Pharmaceutical/methods , Pyridines/chemistry , Pyridines/chemical synthesis , Receptor, Cannabinoid, CB1/agonists , Animals , Behavior, Animal/drug effects , Drug Design , Feeding Behavior/drug effects , Inhibitory Concentration 50 , Models, Chemical , Molecular Conformation , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Temperature , Toluene/chemistry
2.
Bioorg Med Chem Lett
; 12(5): 827-32, 2002 Mar 11.
Article
in English
| MEDLINE
| ID: mdl-11859012
ABSTRACT
A series of 2-arylindoles containing novel heteroaromatic substituents on the tryptamine tether, based on compound 1, was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. Successful modifications of 1 included chain length variation (reduction) and replacement of the pyridine with heteroaromatic groups. These alterations culminated in the discovery of compound 27kk which had excellent in vitro potency and oral efficacy in rodents.
