Derin C D'Amico,
Toshi Aya,
Jason Human,
Christopher Fotsch,
Jian Jeffrey Chen,
Kaustav Biswas,
Bobby Riahi,
Mark H Norman,
Christopher A Willoughby,
Randall Hungate, [......],
James Zhan,
Hideo Suzuki,
Andras Toro,
David A Mareska,
David E Clarke, Darren M Harvey,
Laurence E Burgess,
Ellen R Laird,
Benny Askew,
Gordon Ng
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ABSTRACT: We report the discovery of chroman 28, a potent and selective antagonist of human, nonhuman primate, rat, and rabbit bradykinin B1 receptors (0.4-17 nM). At 90 mg/kg s.c., 28 decreased plasma extravasation in two rodent models of inflammation. A novel method to calculate entropy is introduced and ascribed approximately 30% of the gained affinity between "flexible" 4 (Ki = 132 nM) and "rigid" 28 (Ki = 0.77 nM) to decreased conformational entropy.
Journal of Medicinal Chemistry 03/2007; 50(4):607-10. · 5.25 Impact Factor
