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Design and synthesis of a selective EP4-receptor agonist. Part 2: 3,7-dithiaPGE1 derivatives with high selectivity
Toru Maruyama1, Masaki Asada, Tai Shiraishi
1Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. to.maruyama@ono.co.jp
Abstract:
To identify new highly selective EP4-agonists, further modification of the 16-phenyl moiety of 1 was continued. 16-(3-methoxymethyl)phenyl derivatives 13-(6q) and 16-(3-ethoxymethyl)phenyl derivatives 13-(7e) showed more selectivity and potent agonist activity than 1. 16-(3-methyl-4-hydroxy)phenyl derivative 18-(14e) demonstrated excellent subtype selectivity, while both its receptor affinity and agonist activity were less potent than those of 13-(6q). Structure-activity relationships (SARs) are also discussed.
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