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In an earlier paper, the authors reported that novel prostaglandin D2 (PGD2) receptor antagonists having the bicyclo(2.2.1)heptane ring system as a prostaglandin skeleton were a potent new class of antiallergic agents, and suppressed various allergic inflammatory responses such as those observed in conjunctivitis and asthma models. In the present study, they synthesized PGD2 receptor antagonists having the 6,6-dimethylbicyclo(3.1.1)heptane ring system. These derivatives have the amide moiety, in contrast to those with the bicyclo(2.2.1)heptane ring system, which have the sulfonamide group. The derivatives having the 6,6-dimethylbicyclo(3.1.1)heptane ring also exhibited strong activity in PGD2 receptor binding and cAMP formation assays. In in vivo assays such as allergic rhinitis, conjunctivitis, and asthma models, these series of derivatives showed excellent pharmacological profiles. In particular, compound 45 also effectively suppressed eosinophil infiltration in allergic rhinitis and asthma models. This compound (45, S-5751) is now being developed as a promising alternative antiallergic drug candidate.
Dr. S. Mitsumori, Shionogi Research Laboratories, Shionogi & Co., Ltd., 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan
11.4 Prostaglandins (Part of: 11 Medical treatment)