Discovery of new chemical leads for selective EP1 receptor antagonists.
A series of 4-([2-[alkyl(phenylsulfonyl)amino]phenoxy]methyl)benzoic acids were identified as functional PGE(2) antagonists with selectivity for the EP1 receptor subtype starting from a chemical lead 1, which was found while screening our in-house compound library. Discovery of the optimized analogs 21-23 is presented here and structure-activity relationships (SAR) are also discussed.
Naganawa
Atsushi
A
Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka, Japan. naganawa@ono.co.jp
Saito
Tetsuji
T
Nagao
Yuuki
Y
Egashira
Hiromu
H
Iwahashi
Maki
M
Kambe
Tohru
T
Koketsu
Masatoshi
M
Yamamoto
Hiroshi
H
Kobayashi
Michiyoshi
M
Maruyama
Takayuki
T
Ohuchida
Shuichi
S
Nakai
Hisao
H
Kondo
Kigen
K
Toda
Masaaki
M
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*
D000700:Analgesics; D001565:Benzoates; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013449:Sulfonamides