Discovery of orally active prostaglandin D2 receptor antagonists.
A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D(2) (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented.
Torisu
Kazuhiko
K
Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Osaka, Mishima 618-8585, Japan. torisu@ono.co.jp
Kobayashi
Kaoru
K
Iwahashi
Maki
M
Nakai
Yoshihiko
Y
Onoda
Takahiro
T
Nagase
Toshihiko
T
Sugimoto
Isamu
I
Okada
Yutaka
Y
Matsumoto
Ryoji
R
Nanbu
Fumio
F
Ohuchida
Shuichi
S
Nakai
Hisao
H
Toda
Masaaki
M
D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002199:Capillary Permeability; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D018926:Anti-Allergic Agents; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor