Discovery of Orally Available 8-Aza-5-thiaProstaglandin E1 Analogs as Highly Selective EP4 Agonists

T Kambe, T Maruyama, M Nakano, Y Yamaura…

Index: Kambe, Tohru; Maruyama, Toru; Nakano, Masayuki; Yamaura, Yoshiyuki; Shono, Tomoyuki; Seki, Akiteru; Sakata, Kiyoto; Maruyama, Takayuki; Nakai, Hisao; Toda, Masaaki Chemical and Pharmaceutical Bulletin, 2011 , vol. 59, # 12 p. 1523 - 1534

Full Text: HTML

Citation Number: 7

Abstract

Analogs 8-aza-16-aryl prostaglandin E 1 (PGE 1) and 8-aza-5-thia-16-arylPGE 1 were synthesized and evaluated with respect to their subtype receptor affinity and EP4 agonist activity for the purposes of identifying subtype-selective EP4 agonists that demonstrate oral efficacy. Using an inhibition assay of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production in rats, representative compounds were evaluated for their ...