1.
Bioorg Med Chem Lett
; 23(16): 4517-22, 2013 Aug 15.
Article
in English
| MEDLINE
| ID: mdl-23850198
ABSTRACT
The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochemical and cellular mechanistic potency to ~10nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.
Subject(s)
MAP Kinase Kinase Kinases/antagonists & inhibitors , Pyridines , Amines/chemical synthesis , Amines/chemistry , Amines/pharmacology , Animals , Crystallography, X-Ray , Drug Design , Enzyme Activation/drug effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacokinetics , Enzyme Inhibitors/pharmacology , Furans/chemical synthesis , Furans/chemistry , Furans/pharmacology , Humans , Inhibitory Concentration 50 , Mice , Molecular Structure , Neoplasms/drug therapy , Pyridines/chemical synthesis , Pyridines/pharmacokinetics , Pyridines/pharmacology , Structure-Activity Relationship , Xenograft Model Antitumor Assays
2.
Rev Med Panama
; 27: 41-4, 2002.
Article
in Spanish
| MEDLINE
| ID: mdl-16737199
