A novel series of 2-pyridyl-containing compounds as lysophosphatidic acid receptor antagonists: development of a nonhydrolyzable LPA 3 receptor-selective antagonist

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 15; pp. 4069 - 4074
• Main Authors: Heasley, Brian H, Jarosz, Renata, Carter, Karen M, Jenny Van, S, Lynch, Kevin R, Macdonald, Timothy L
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2004
• Subjects: Lysophosphatidic acid receptor antagonist; Lysophosphatidic acid receptor antagonist
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.05.023

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. This study has resulted in the development of the first nonhydrolyzable and presumably phosphatase-resistant LPA 3-selective antagonist ( 13d) reported to date. 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.