Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369513 | Bioorganic & Medicinal Chemistry Letters | 2016 | 5 Pages |
Abstract
The structure of the S1P2 antagonist 1 has been modified with the aim of improving its oral bioavailability. The chemical modification of the alkyl chain and carboxylic acid moieties of 1 led to significant improvements in the oral exposure of compounds belonging to this series. The optimization of the ring size of the urea portion of these molecules also led to remarkable improvements in the oral exposure. Based on these changes, the pyrrolidine derivative 16 was identified as a suitable candidate compound and showed excellent pharmacokinetic profiles in rat and dog, while maintaining high levels of potency and selective antagonistic activity toward S1P2.
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Related Topics
Physical Sciences and Engineering
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Organic Chemistry
Authors
Kensuke Kusumi, Koji Shinozaki, Yoshiyuki Yamaura, Ai Hashimoto, Haruto Kurata, Atsushi Naganawa, Kazuhiro Otsuki, Takeshi Matsushita, Tetsuya Sekiguchi, Akito Kakuuchi, Hiroshi Yamamoto, Takuya Seko,