Author/Authors :
Kousuke Tani، نويسنده , , Atsushi Naganawa، نويسنده , , Akiharu Ishida، نويسنده , , Hiromu Egashira، نويسنده , , Kenji Sagawa، نويسنده , , Hiroyuki Harada، نويسنده , , Mikio Ogawa، نويسنده , , Takayuki Maruyama، نويسنده , , Shuichi Ohuchida، نويسنده , , Hisao Nakai، نويسنده , , Kigen Kondo، نويسنده , , Masaaki Toda، نويسنده ,
Abstract :
Further chemical modification of 1a and 2 was undertaken to identify a more chemically stable selective EP2-receptor agonist for development as a clinical candidate. 9β-Chloro PG analogues 4a–e and 5a, c–e were found to be potent and selective EP2-receptor agonists. Among them, the compound 4aLy, which is a chemically stabilized lysine salt of 4a, exhibited an excellent profile both in biological activities and physicochemical properties. The agonist 4aLy was found to suppress uterine motility in anesthetized pregnant rats, while PGE2 stimulated uterine motility. Structure–activity relationships (SARs) are discussed.
