2. Academic Validation
  3. Development of a highly selective EP2-receptor agonist. Part 2: identification of 16-hydroxy-17,17-trimethylene 9beta-chloro PGF derivatives

Development of a highly selective EP2-receptor agonist. Part 2: identification of 16-hydroxy-17,17-trimethylene 9beta-chloro PGF derivatives

  • Bioorg Med Chem. 2002 Apr;10(4):1107-14. doi: 10.1016/s0968-0896(01)00370-4.
Kousuke Tani 1,  Atsushi Naganawa,  Akiharu Ishida,  Hiromu Egashira,  Kenji Sagawa,  Hiroyuki Harada,  Mikio Ogawa,  Takayuki Maruyama,  Shuichi Ohuchida,  Hisao Nakai,  Kigen Kondo,  Masaaki Toda
Affiliations

Affiliation

  • 1 Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. [email protected]
PMID: 11836121 DOI: 10.1016/s0968-0896(01)00370-4
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. 9beta-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.

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