advertisement
Abstract #8981 Published in IGR 5-2
Synthesis and biological activity of various derivatives of a novel class of potent, selective, and orally active prostaglandin D2 receptor antagonists. 1. Bicyclo(2.2.1)heptane derivatives
Mitsumori S; Tsuri T; Honma T; Hiramatsu Y; Okada T; Hashizume H; Inagaki M; Arimura A; Yasui K; Asanuma FJournal of Medicinal Chemistry 2003; 46: 2436-2445
Novel prostaglandin D2l (PGD2) receptor antagonists were synthesized as a potential new class of antiallergic agents having a bicyclo(2.2.1)heptane ring system with sulfonamide groups. Some of them exhibit extremely potent antagonism of the PGD2 receptor in radioligand binding and cAMP formation assays with IC50 values below 50 nm and much less antagonism of TXA2 and PGI2 receptors. These potent PGD2 receptor antagonists, when given orally, dramatically suppress various allergic inflammatory responses such as increased vascular permeability in allergic rhinitis, conjunctivitis, and asthma models. The excellent pharmacological profiles of PGD2 receptor antagonists, originally synthesized in the authors' laboratories, are of potentially great clinical significance. This study also provides experimental evidence suggesting that PGD2 plays an important role in the pathogenesis of allergic diseases.
Dr. S. Mitsumori, Shionogi Research Laboratories, Shionogi & Co., Ltd., 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
