Design and synthesis of a selective EP4-receptor agonist. Part 4: practical synthesis and biological evaluation of a novel highly selective EP4-receptor agonist.
A practical method of synthesizing a highly selective EP4-receptor agonist 1 using Corey lactone 2 as a key intermediate was developed. Selective methanesulfonylation of the primary alcohol of the diol 8 under the newly devised conditions followed by the protection of the remaining secondary alcohol are key reactions in this new method. Further biological evaluation of 1a-b is also reported.
Maruyama
Toru
T
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, Osaka 618-8585, Japan. to.maruyama@ono.co.jp
Kuwabe
Shin-Itsu
SI
Kawanaka
Yasufumi
Y
Shiraishi
Tai
T
Shinagawa
Yoshiyuki
Y
Sakata
Kiyoto
K
Seki
Akiteru
A
Kishida
Yoko
Y
Yoshida
Hideyuki
H
Maruyama
Takayuki
T
Ohuchida
Shuichi
S
Nakai
Hisao
H
Hashimoto
Shinsuke
S
Kawamura
Masanori
M
Kondo
Kigen
K
Toda
Masaaki
M
D000818:Animals; D001773:Blood Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015398:Signal Transduction; D013057:Spectrum Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; C545650:PTGER4 protein, human; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10