1. Alpha-hydroxy amides as a novel class of bradykinin B1 selective antagonists.
- Author
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Wood MR, Schirripa KM, Kim JJ, Kuduk SD, Chang RK, Di Marco CN, DiPardo RM, Wan BL, Murphy KL, Ransom RW, Chang RS, Holahan MA, Cook JJ, Lemaire W, Mosser SD, Bednar RA, Tang C, Prueksaritanont T, Wallace AA, Mei Q, Yu J, Bohn DL, Clayton FC, Adarayn ED, Sitko GR, Leonard YM, Freidinger RM, Pettibone DJ, and Bock MG
- Subjects
- Amides chemistry, Amides pharmacokinetics, Animals, Biological Availability, Blood-Brain Barrier, Cytochrome P-450 Enzyme Inhibitors, Dogs, Half-Life, Humans, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Amides pharmacology, Bradykinin B1 Receptor Antagonists
- Abstract
Antagonism of the bradykinin B(1) receptor represents a potential treatment for chronic pain and inflammation. Novel antagonists incorporating alpha-hydroxy amides were designed that display low-nanomolar affinity for the human bradykinin B(1) receptor and good bioavailability in the rat and dog. In addition, these functionally active compounds show high passive permeability and low susceptibility to phosphoglycoprotein mediated efflux, predictive of good CNS exposure.
- Published
- 2008
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