Synthesis and structure–activity relationships of tyrosine-based inhibitors of autotaxin (ATX)

Autor:	Andrew J. Kennedy, James E. East, Timothy L. Macdonald, Kevin R. Lynch, Jose L. Tomsig, Alexandra R. De Leon
Rok vydání:	2010
Předmět:	Pyridines Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Biochemistry Article Structure-Activity Relationship chemistry.chemical_compound Biosynthesis Multienzyme Complexes Drug Discovery Lysophosphatidic acid Humans Structure–activity relationship Enzyme Inhibitors Pyrophosphatases Tyrosine Molecular Biology chemistry.chemical_classification Phosphoric Diester Hydrolases Organic Chemistry In vitro Enzyme chemistry Phosphodiesterase I Alkylglycerophosphoethanolamine phosphodiesterase Molecular Medicine lipids (amino acids peptides and proteins) Lysophospholipids biological phenomena cell phenomena and immunity Autotaxin
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 20:7132-7136
ISSN:	0960-894X
Popis:	Autotaxin (ATX) is a secreted soluble enzyme that generates lysophosphatidic acid (LPA) through its lysophospholipase D activity. Because of LPA’s role in neoplastic diseases, ATX is an attractive therapeutic target due to its involvement in LPA biosynthesis. Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6123ca063e5d06b5723110ab866bbb5 https://doi.org/10.1016/j.bmcl.2010.09.030 Zobrazit plný text záznamu Full Text from ScienceDirect