III. Identification of novel CXCR3 chemokine receptor antagonists with a pyrazinyl–piperazinyl–piperidine scaffold

Autor:	Xiaolian Xu, Seong Heon Kim, Qingbei Zeng, Joseph A. Kozlowski, Carolyn DiIanni Carroll, Neng-Yang Shih, Baldwin John J, Wensheng Yu, Yueheng Jiang, Guizhen Dong, Yuefei Shao, Brian F. Mcguinness, Gopinadhan N. Anilkumar, Lisa Guise Zawacki, Doug W. Hobbs, Chung-Her Jenh, James W. Hall, Stuart B. Rosenblum, Bandarpalle B. Shankar, De-Yi Yang
Rok vydání:	2011
Předmět:	congenital hereditary and neonatal diseases and abnormalities Receptors CXCR3 Clinical Biochemistry hERG Pharmaceutical Science C-C chemokine receptor type 7 C-C chemokine receptor type 6 CCR5 receptor antagonist Pharmacology Biochemistry Piperazines Inhibitory Concentration 50 Structure-Activity Relationship Chemokine receptor stomatognathic system Drug Discovery Animals Structure–activity relationship cardiovascular diseases skin and connective tissue diseases Molecular Biology Molecular Structure biology Chemistry Organic Chemistry Rats stomatognathic diseases Pyrazines biology.protein Molecular Medicine Receptor antagonist activity Protein Binding CCL21
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:6982-6986
ISSN:	0960-894X
Popis:	The SAR of a novel pyrazinyl-piperazinyl-piperidine scaffold with CXCR3 receptor antagonist activity was explored. Optimization of the DMPK profile and reduction of hERG inhibition is described. Compound 16e with single-digit CXCR3 affinity, good rat PK and hERG profiles has been identified as a lead for further study.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c65b7371750c0100d6b469612e6fd2f https://doi.org/10.1016/j.bmcl.2011.09.120 Zobrazit plný text záznamu Full Text from ScienceDirect