title: A novel series of 2-pyridyl-containing compounds as lysophosphatidic acid receptor antagonists: development of a nonhydrolyzable LPA3 receptor-selective antagonist.
abstract: A recently reported dual LPA(1)/LPA(3) receptor antagonist (1) has been modified so as to modulate the basicity, sterics, and dipole moment of the 2-pyridyl moiety. Additionally, the implications of installing nonhydrolyzable phosphate head group isosteres with regard to antagonist potency and selectivity at LPA receptors is described. This study has resulted in the development of the first nonhydrolyzable and presumably phosphatase-resistant LPA(3)-selective antagonist reported to date.
authors.affiliation: Department of Chemistry, University of Virginia, PO Box 400319, McCormick Road, Charlottesville, VA 22904, USA. bhh4x@virginia.edu
authors.forename: Brian H
authors.initials: BH
authors.lastname: Heasley
authors.forename: Renata
authors.initials: R
authors.lastname: Jarosz
authors.forename: Karen M
authors.initials: KM
authors.lastname: Carter
authors.forename: S Jenny
authors.initials: SJ
authors.lastname: Van
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Lynch
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D011725:Pyridines; D049368:Receptors, Lysophosphatidic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate)