1.
Bioorg Med Chem Lett
; 15(23): 5293-7, 2005 Dec 01.
Article
in English
| MEDLINE
| ID: mdl-16203136
ABSTRACT
The synthesis and biological evaluation of novel 3-amino indazole melanin concentrating hormone receptor-1 antagonists are reported, several of which demonstrated functional activity of less than 100nM. Compounds 19 and 28, two of the more potent compounds identified in this study, were characterized by high exposure in the brain and demonstrated robust efficacy when dosed in diet-induced obese mice.
Subject(s)
Anti-Obesity Agents/chemical synthesis , Anti-Obesity Agents/pharmacology , Indazoles/chemical synthesis , Indazoles/pharmacology , Receptors, Somatostatin/antagonists & inhibitors , Administration, Oral , Animals , Anti-Obesity Agents/administration & dosage , Humans , Indazoles/administration & dosage , Mice , Piperidines/chemistry , Tissue Distribution
2.
Bioorg Med Chem Lett
; 15(19): 4174-9, 2005 Oct 01.
Article
in English
| MEDLINE
| ID: mdl-16085414
ABSTRACT
Several potent and efficacious MCHr1 antagonists containing an ortho-amino benzamide or nicotinamide chemotype have been identified, exemplified by 28 and 50.
Subject(s)
Niacinamide/analogs & derivatives , Receptors, Somatostatin/antagonists & inhibitors , ortho-Aminobenzoates/chemical synthesis , Animals , Benzamides/chemical synthesis , Benzamides/pharmacokinetics , Benzamides/pharmacology , Inhibitory Concentration 50 , Mice , Mice, Inbred Strains , Niacinamide/pharmacokinetics , Niacinamide/pharmacology , Pharmacokinetics , Receptors, Somatostatin/agonists , Structure-Activity Relationship , Tissue Distribution , ortho-Aminobenzoates/pharmacokinetics , ortho-Aminobenzoates/pharmacology
3.
Bioorg Med Chem Lett
; 15(14): 3412-6, 2005 Jul 15.
Article
in English
| MEDLINE
| ID: mdl-15950463
ABSTRACT
The identification of a novel series of benzamide-containing MCHr1 antagonists is described. Compound 22 displayed moderate efficacy in a diet induced obesity mice model.
