Development of Orally Bioavailable and CNS Penetrant Biphenylaminocyclopropane Carboxamide Bradykinin B 1 Receptor Antagonists
Journal of Medicinal Chemistry2006Vol. 50(2), pp. 272–282
Citations Over TimeTop 10% of 2006 papers
Scott D. Kuduk, Christina N. Di Marco, Ronald K. Chang, Michael R. Wood, Kathy M. Schirripa, June J. Kim, Jenny Wai, Robert M. DiPardo, Kathy Murphy, Richard W. Ransom, C. Meacham Harrell, Duane R. Reiss, Marie A. Holahan, Jacquelynn J. Cook, J. Fred Hess, Nova Sain, Mark O. Urban, Cuyue Tang, Thomayant Prueksaritanont, Douglas J. Pettibone, Mark G. Bock
Abstract
A series of biphenylaminocyclopropane carboxamide based bradykinin B1 receptor antagonists has been developed that possesses good pharmacokinetic properties and is CNS penetrant. Discovery that the replacement of the trifluoropropionamide in the lead structure with polyhaloacetamides, particularly a trifluoroacetamide, significantly reduced P-glycoprotein mediated efflux for the series proved essential. One of these novel bradykinin B1 antagonists (13b) also exhibited suitable pharmacokinetic properties and efficient ex vivo receptor occupancy for further development as a novel approach for the treatment of pain and inflammation.
Related Papers
- → Solute and penetrant diffusion in swellable polymers. I. Mathematical modeling(1986)254 cited
- → A genetic platform to investigate the functions of bacterial drug efflux pumps(2022)45 cited
- → Effect of penetrant–polymer interactions and shape on the motion of molecular penetrants in dense polymer networks(2024)5 cited
- → Solute and penetrant diffusion in swellable polymers(1988)28 cited
- → Diffusion time–temperature superposition of various penetrant–adhesive systems: correlations between penetrant structure, diffusivity, and dynamic mechanical response. III(2003)4 cited