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Ikubo, Masaya; Uwamizu, Akiharu; Chen, Luying; Nakamura, Sho; Sayama, Misa; Kawana, Hiroki; Otani, Yuko; Kano, Kuniyuki; Inoue, Asuka; Aoki, Junken; Ohwada, Tomohiko
Chemical & pharmaceutical bulletin, 07/2023, Letnik: 71, Številka: 7Journal Article
Our group has reported various derivatives of lysophosphatidylserine (LysoPS) as potent and subtype-selective agonists for G-protein-coupled receptors (GPCRs). However, the ester linkage between the glycerol moiety and fatty acid or fatty acid surrogate is present in all of them. In order to develop these LysoPS analogs as drug candidates, appropriate pharmacokinetic consideration is essential. Here, we found that the ester bond of LysoPS is highly susceptible to metabolic degradation in mouse blood. Accordingly, we examined isosteric replacement of the ester linkage with heteroaromatic rings. The resulting compounds showed excellent retention of potency and receptor subtype selectivity, as well as increased metabolic stability in vitro.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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