A novel series of 2-pyridyl-containing compounds as lysophosphatidic acid receptor antagonists: development of a nonhydrolyzable LPA3 receptor-selective antagonist.
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.
Heasley
Brian H
BH
Department of Chemistry, University of Virginia, PO Box 400319, McCormick Road, Charlottesville, VA 22904, USA. bhh4x@virginia.edu
Jarosz
Renata
R
Carter
Karen M
KM
Van
S Jenny
SJ
Lynch
Kevin R
KR
Macdonald
Timothy L
TL
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
D011725:Pyridines; D049368:Receptors, Lysophosphatidic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate)