Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity

Autor:	Robert R. Lavieri, Jana A. Lewis, Paige E. Selvy, Michelle D. Armstrong, Jason R. Buck, Craig W. Lindsley, H. Alex Brown, Sydney L. Stoops, Sarah A. Scott
Rok vydání:	2009
Předmět:	Gene isoform Halogenation medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Carboxamide Biochemistry Chemical synthesis Article Cell Line Substrate Specificity Structure-Activity Relationship Drug Discovery Phospholipase D medicine Humans Protein Isoforms Structure–activity relationship Enzyme Inhibitors Molecular Biology chemistry.chemical_classification PLD2 Organic Chemistry Phosphoric Diester Hydrolases Domperidone Enzyme chemistry Drug Design Molecular Medicine Benzimidazoles lipids (amino acids peptides and proteins)
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:1916-1920
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2009.02.057
Popis:	This Letter describes the synthesis and structure-activity-relationships (SAR) of isoform-selective PLD inhibitors. By virtue of the installation of alternative halogenated piperidinyl benzimidazolone privileged structures, in combination with a key (S)-methyl group, novel PLD inhibitors with low nM potency and unprecedented levels of PLD1 isoform selectivity (approximately 1700-fold) over PLD2 were developed.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6825f7944ffc4a46c8fc4bb195842ab7 https://doi.org/10.1016/j.bmcl.2009.02.057 Zobrazit plný text záznamu Full Text from ScienceDirect