Trimethylsilylpyrazoles as novel inhibitors of p38 MAP kinase: a new use of silicon bioisosteres in medicinal chemistry.
The synthesis, physicochemical properties and pharmacological profiles of two novel silicon-containing p38 MAP kinase inhibitors are described.
Barnes
Matthew J
MJ
Paradigm Therapeutics Ltd, 418 Cambridge Science Park, Milton Road, Cambridge CB4 0PA, UK.
Conroy
Richard
R
Miller
David J
DJ
Mills
John S
JS
Montana
John G
JG
Pooni
Parminder K
PK
Showell
Graham A
GA
Walsh
Louise M
LM
Warneck
Julie B H
JB
D000818:Animals; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D017655:Silicon Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D011720:Pyrazoles; D017655:Silicon Compounds; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases