Design and synthesis of dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole oximes as potent dual inhibitors of TIE-2 and VEGF-R2 receptor tyrosine kinases

Autor:	Edward R. Bacon, Robert L. Hudkins, Thelma S. Angeles, Jennifer Grobelny, Mark S. Albom, Reddeppareddy Dandu, Bruce Ruggeri, Sheila J. Miknyoczki, Lisa D. Aimone, Shi Yang, Candy Robinson, Hong Chang, Allison L. Zulli, Ted L. Underiner
Rok vydání:	2008
Předmět:	Umbilical Veins Hemangiosarcoma Clinical Biochemistry Melanoma Experimental Administration Oral Pharmaceutical Science Angiogenesis Inhibitors Biochemistry Chemical synthesis Receptor tyrosine kinase Structure-Activity Relationship chemistry.chemical_compound Oximes Drug Discovery Animals Humans Structure–activity relationship Receptor Protein Kinase Inhibitors Molecular Biology Cells Cultured Cell Proliferation chemistry.chemical_classification Molecular Structure Neovascularization Pathologic biology Organic Chemistry Oxime Receptor TIE-2 Vascular Endothelial Growth Factor Receptor-2 Rats Enzyme chemistry Enzyme inhibitor Drug Design biology.protein Molecular Medicine Endothelium Vascular Signal transduction
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 18:1916-1921
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2008.02.001
Popis:	Fused dihydroindazolopyrrolocarbazole oximes have been identified as low nanomolar, potent dual TIE-2 and VEGF-R2 receptor tyrosine kinase inhibitors with excellent cellular potency. Development of the structure-activity relationships (SAR) led to identification of compounds 35 and 40 as potent, selective dual TIE-2/VEGF-R2 inhibitors with favorable pharmacokinetic properties. Compound 35 was orally active in tumor models with no observed toxicity.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff81dd5bd91b90c842800ca27629d74b https://doi.org/10.1016/j.bmcl.2008.02.001 Zobrazit plný text záznamu Full Text from ScienceDirect