Discovery and synthesis of novel 4-aminopyrrolopyrimidine Tie-2 kinase inhibitors for the treatment of solid tumors

Autor:	Jean S. Beebe, William M. Hungerford, Nandini Chaturbhai Patel, Heather N. Frost, Susan Deborah Lagreca, Cathy Soderstrom, Shefali Kakar, Doug Savage, Matthew David Wessel, Matthew A. Marx, Merin Boehm, Thompson Carl Brian, Jinshan M. Chen, Connell Richard D, Nandell F. Keene, Elizabeth Knauth, Gary Borzillo, Aaron Kanter, Yong Lu, Joel Morris, Martin A. Berliner, Patrick Vincent, Bruce D. Cohen, George T. Tkalcevic, Joel T. Arcari, Deborah A. Gordon, James J. Valentine, Tracey Clark, Louis Martinez-Alsina, Vincent Bernardo, Felix Vajdos, Norma Jacqueline Tom
Rok vydání:	2013
Předmět:	Male Benzimidazole Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biochemistry Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Neoplasms Drug Discovery Animals Humans Structure–activity relationship Pyrroles Protein Kinase Inhibitors Molecular Biology Cell Proliferation 4-aminopyrrolopyrimidine Dose-Response Relationship Drug Molecular Structure Drug discovery Kinase Organic Chemistry Receptor TIE-2 Xenograft Model Antitumor Assays In vitro Rats Pyrimidines chemistry Cell culture Molecular Medicine Growth inhibition
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 23:3059-3063
ISSN:	0960-894X
Popis:	The synthesis and biological evaluation of novel Tie-2 kinase inhibitors are presented. Based on the pyrrolopyrimidine chemotype, several new series are described, including the benzimidazole series by linking a benzimidazole to the C5-position of the 4-amino-pyrrolopyrimidine core and the ketophenyl series synthesized by incorporating a ketophenyl group to the C5-position. Medicinal chemistry efforts led to potent Tie-2 inhibitors. Compound 15, a ketophenyl pyrrolopyrimidine urea analog with improved physicochemical properties, demonstrated favorable in vitro attributes as well as dose responsive and robust oral tumor growth inhibition in animal models.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4094fb50746e9612e49cef7a5bc7bf6 https://doi.org/10.1016/j.bmcl.2013.03.012 Zobrazit plný text záznamu Full Text from ScienceDirect