1.
Bioorg Med Chem Lett
; 17(7): 1996-9, 2007 Apr 01.
Article
in English
| MEDLINE
| ID: mdl-17276061
ABSTRACT
The synthesis of a novel gut selective MTP inhibitor, 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), and its in vitro and in vivo profile are described. Dirlotapide (3) demonstrated excellent potency against MTP enzyme in HepG2 cells and canine hepatocytes. This novel MTP inhibitor also showed excellent efficacy when tested in a canine food intake model.
Subject(s)
Carbamates/chemical synthesis , Carboxylic Acids/chemistry , Carboxylic Acids/chemical synthesis , Carrier Proteins/antagonists & inhibitors , Chemistry, Pharmaceutical/methods , Indoles/chemical synthesis , Obesity/drug therapy , Animals , Carbamates/chemistry , Carbamates/pharmacology , Carboxylic Acids/pharmacology , Dogs , Drug Design , Drug Evaluation, Preclinical , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Indoles/chemistry , Indoles/pharmacology , Inhibitory Concentration 50 , Models, Chemical , Molecular Conformation , Rats
2.
Bioorg Med Chem Lett
; 12(17): 2431-4, 2002 Sep 02.
Article
in English
| MEDLINE
| ID: mdl-12161150
ABSTRACT
3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria.