Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): Kinase profiling guided optimization of a 1,2,3-benzotriazole lead

Autor:	R. Ursula Kammlott, Deborah Carol Reuter, Teresa Alejandra Trejo-Martin, Leyi Gong, Christophe Michoud, Andreas Kuglstatter, Patricia Tran, David Michael Goldstein, Yun-Chou Tan, Parcharee Tivitmahaisoon, Linghao Niu, Shao-Yong Wu, Sue Jin, Paul Weller, Gary Hsieh, Karin Ann Stein, Humberto Bartolome Arzeno, James Patrick Dunn, Ada Shao, Wylie Solang Palmer, J. Heather Hogg, Johannes C. Hermann, Kung-ching Chang, Bindu Goyal, Alam Jahangir, Cheryl Janson, Tania Silva, Christine Lukacs, Paul J. Wagner, Muzaffar Alam
Rok vydání:	2013
Předmět:	Models Molecular Pyrimidine Clinical Biochemistry Pharmaceutical Science Pharmacology Crystallography X-Ray Biochemistry Structure-Activity Relationship chemistry.chemical_compound In vivo Drug Discovery Animals Humans Structure–activity relationship Protein Kinase Inhibitors Molecular Biology Benzotriazole biology Kinase Organic Chemistry Cyclin-dependent kinase 2 c-jun JNK Mitogen-Activated Protein Kinases Triazoles Rats Bioavailability Pyrimidines chemistry Drug Design biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 23:1486-1492
ISSN:	0960-894X
Popis:	A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, respectively), with bioavailability in rats and suitable for further in vivo pharmacological evaluation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1b003a69164deb7db8c54e3d4d75bb7b https://doi.org/10.1016/j.bmcl.2012.12.047 Zobrazit plný text záznamu Full Text from ScienceDirect