Discovery of diarylurea P2Y(1) antagonists with improved aqueous solubility

Bioorg Med Chem Lett. 2013 Jun 1;23(11):3239-43. doi: 10.1016/j.bmcl.2013.03.125.

Tammy C Wang ¹, Jennifer X Qiao, Charles G Clark, Ji Jua, Laura A Price, Qimin Wu, Ming Chang, Joanna Zheng, Christine S Huang, Gerry Everlof, William A Schumacher, Pancras C Wong, Dietmar A Seiffert, Anne B Stewart, Jeffrey S Bostwick, Earl J Crain, Carol A Watson, Robert Rehfuss, Ruth R Wexler, Patrick Y S Lam

Affiliations

Affiliation

1 Medicinal Chemistry, Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb, 311 Pennington-Rocky Hill Road, Pennington, NJ 08534, USA.

PMID: 23602442 DOI: 10.1016/j.bmcl.2013.03.125

Abstract

Preclinical data suggests that P2Y1 antagonists, such as diarylurea compound 1, may provide antithrombotic efficacy similar to P2Y12 antagonists and may have the potential of providing reduced bleeding liabilities. This manuscript describes a series of diarylureas bearing solublizing amine side chains as potent P2Y1 antagonists. Among them, compounds 2l and 3h had improved aqueous solubility and maintained antiplatelet activity compared with compound 1. Compound 2l was moderately efficacious in both rat and rabbit thrombosis models and had a moderate prolongation of bleeding time in rats similar to that of compound 1.

Name
Email *

	Sorry, but the email address you supplied was invalid.