Development of prostaglandin D2 receptor antagonist: discovery of highly potent antagonists.
The process of discovery for highly potent prostaglandin D(2) (PGD(2)) receptor antagonists is reported. A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and identified as a new class of selective PGD(2) receptor antagonists. Most of them exhibited strong PGD(2) receptor antagonism in binding studies and the cAMP formation assay. The structure-activity relationships (SAR), including subtype selectivity of the synthesized compounds, are also discussed.
Torisu
Kazuhiko
K
Minase Research Institute, Ono Pharmaceutical Co. Ltd., Shimamoto, Mishima, Osaka 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
Masaaki Toda
D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism; D015195:Drug Design; D007210:Indoleacetic Acids / Q000737:chemistry / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D018926:Anti-Allergic Agents; D007210:Indoleacetic Acids; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; C036293:prostaglandin D2 receptor