1.
Bioorg Med Chem Lett
; 21(23): 7006-12, 2011 Dec 01.
Article
in English
| MEDLINE
| ID: mdl-22018461
ABSTRACT
The synthesis, structure-activity relationships (SAR), and biological results of pyridyl-substituted azaindole based tricyclic inhibitors of IKK2 are described. Compound 4m demonstrated potent in vitro potency, acceptable pharmacokinetic and physicochemical properties, and efficacy when dosed orally in a mouse model of inflammatory bowel disease.
Subject(s)
Acetamides/chemistry , Drug Discovery , Enzyme Inhibitors/chemistry , Heterocyclic Compounds, 3-Ring/chemistry , I-kappa B Kinase/antagonists & inhibitors , Acetamides/chemical synthesis , Acetamides/pharmacology , Administration, Oral , Animals , Enzyme Activation/drug effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Heterocyclic Compounds, 3-Ring/chemical synthesis , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , Inflammatory Bowel Diseases/drug therapy , Inhibitory Concentration 50 , Mice , Molecular Structure , Rats , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 12(21): 3125-8, 2002 Nov 04.
Article
in English
| MEDLINE
| ID: mdl-12372516
ABSTRACT
A series of heterocyclic replacements for the central diamide moiety of 1, a potent small molecule inhibitor of inosine monophosphate dehydrogenase (IMPDH) were explored The synthesis and the structure-activity relationships (SARs), derived from in vitro studies, for these new series of inhibitors is given.
