Potent 2-[(pyrimidin-4-yl)amine}-1,3-thiazole-5-carbonitrile-based inhibitors of VEGFR-2 (KDR) kinase.

Sisko, John T; Tucker, Thomas J; Bilodeau, Mark T; Buser, Carolyn A; Ciecko, Patrice A; Coll, Kathleen E; Fernandes, Christine; Gibbs, Jackson B; Koester, Timothy J; Kohl, Nancy; Lynch, Joseph J; Mao, Xianzhi; McLoughlin, Debra; Miller-Stein, Cynthia M; Rodman, Leonard D; Rickert, Keith W; Sepp-Lorenzino, Laura; Shipman, Jennifer M; Thomas, Kenneth A; Wong, Bradley K; Hartman, George D

Sisko, John T; Tucker, Thomas J; Bilodeau, Mark T; Buser, Carolyn A; Ciecko, Patrice A; Coll, Kathleen E; Fernandes, Christine; Gibbs, Jackson B; Koester, Timothy J; Kohl, Nancy; Lynch, Joseph J; Mao, Xianzhi; McLoughlin, Debra; Miller-Stein, Cynthia M; Rodman, Leonard D; Rickert, Keith W; Sepp-Lorenzino, Laura; Shipman, Jennifer M; Thomas, Kenneth A; Wong, Bradley K; Hartman, George D.

Affiliation

Sisko JT; Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. jack_sisko@merck.com

Bioorg Med Chem Lett ; 16(5): 1146-50, 2006 Mar 01.

Article in En | MEDLINE | ID: mdl-16368234

ABSTRACT

ABSTRACT

Pyrimidino-thiazolyl carbonitriles were prepared that are potent VEGFR-2 (KDR) kinase inhibitors. The modification of lead structures resulted in 3m which exhibited the best overall profile in KDR inhibitory activity, iv/po pharmacokinetics, and reduced hERG affinity.

Subject(s)

Nitriles/chemical synthesis; Nitriles/pharmacology; Protein Kinase Inhibitors/chemical synthesis; Protein Kinase Inhibitors/pharmacology; Pyrimidines/chemical synthesis; Pyrimidines/pharmacology; Thiazoles/chemical synthesis; Thiazoles/pharmacology; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors; Animals; Dogs; Macaca mulatta; Molecular Structure; Nitriles/chemistry; Protein Kinase Inhibitors/chemistry; Pyrimidines/chemistry; Rats; Sensitivity and Specificity; Structure-Activity Relationship; Thiazoles/chemistry; Vascular Endothelial Growth Factor Receptor-2/metabolism

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Collection: 01-internacional Database: MEDLINE Main subject: Pyrimidines / Thiazoles / Vascular Endothelial Growth Factor Receptor-2 / Protein Kinase Inhibitors / Nitriles Type of study: Diagnostic_studies Limits: Animals Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2006 Document type: Article Affiliation country: United States Publication country: ENGLAND / ESCOCIA / GB / GREAT BRITAIN / INGLATERRA / REINO UNIDO / SCOTLAND / UK / UNITED KINGDOM

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