1. Discovery of pyrrolo[2,1-f][1,2,4]triazine C6-ketones as potent, orally active p38α MAP kinase inhibitors.
- Author
-
Dyckman AJ, Li T, Pitt S, Zhang R, Shen DR, McIntyre KW, Gillooly KM, Shuster DJ, Doweyko AM, Sack JS, Kish K, Kiefer SE, Newitt JA, Zhang H, Marathe PH, McKinnon M, Barrish JC, Dodd JH, Schieven GL, and Leftheris K
- Subjects
- Administration, Oral, Animals, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Arthritis drug therapy, Binding Sites, Crystallography, X-Ray, Disease Models, Animal, Drug Evaluation, Preclinical, Female, Mice, Mitogen-Activated Protein Kinase 14 metabolism, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Protein Structure, Tertiary, Rats, Structure-Activity Relationship, Triazines pharmacology, Triazines therapeutic use, Anti-Inflammatory Agents chemistry, Mitogen-Activated Protein Kinase 14 antagonists & inhibitors, Protein Kinase Inhibitors chemistry, Pyrroles chemistry, Triazines chemistry
- Abstract
Pyrrolo[2,1-f][1,2,4]triazine based inhibitors of p38α have been prepared exploring functional group modifications at the C6 position. Incorporation of aryl and heteroaryl ketones at this position led to potent inhibitors with efficacy in in vivo models of acute and chronic inflammation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF