A rational chemical intervention strategy to circumvent bioactivation liabilities associated with a nonpeptidyl thrombopoietin receptor agonist containing a 2-amino-4-arylthiazole motif.

Kalgutkar, Amit S; Driscoll, James; Zhao, Sabrina X; Walker, Gregory S; Shepard, Richard M; Soglia, John R; Atherton, James; Yu, Linning; Mutlib, Abdul E; Munchhof, Michael J; Reiter, Lawrence A; Jones, Christopher S; Doty, Johnathan L; Trevena, Kristen A; Shaffer, Christopher L; Ripp, Sharon L

Kalgutkar, Amit S; Driscoll, James; Zhao, Sabrina X; Walker, Gregory S; Shepard, Richard M; Soglia, John R; Atherton, James; Yu, Linning; Mutlib, Abdul E; Munchhof, Michael J; Reiter, Lawrence A; Jones, Christopher S; Doty, Johnathan L; Trevena, Kristen A; Shaffer, Christopher L; Ripp, Sharon L.

Affiliation

Kalgutkar AS; Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, Connecticut 06340, USA. amit.kalgutkar@pfizer.com

Chem Res Toxicol ; 20(12): 1954-65, 2007 Dec.

Article in En | MEDLINE | ID: mdl-17935300

Subject(s)

Pyridines/pharmacology; Receptors, Thrombopoietin/agonists; Thiazoles/chemistry; Animals; Biological Availability; Biotransformation; Cell Line; Drug Stability; Glutathione/metabolism; Hepatocytes/metabolism; Humans; Male; Mice; Microsomes, Liver/metabolism; Molecular Structure; Pyridines/blood; Pyridines/chemistry; Pyridines/metabolism; Rats; Rats, Sprague-Dawley; Receptors, Thrombopoietin/genetics; Thiazoles/blood; Thiazoles/metabolism; Thiazoles/pharmacology; Transfection

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Database: MEDLINE Main subject: Pyridines / Thiazoles / Receptors, Thrombopoietin Type of study: Risk_factors_studies Limits: Animals / Humans / Male Language: En Year: 2007 Type: Article

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