1186335-77-2Relevant academic research and scientific papers
Anti-influenza activity of phenethylphenylphthalimide analogs derived from thalidomide
Iwai, Yuma,Takahashi, Hitoshi,Hatakeyama, Dai,Motoshima, Kazunori,Ishikawa, Minoru,Sugita, Kazuyuki,Hashimoto, Yuichi,Harada, Yuichi,Itamura, Shigeyuki,Odagiri, Takato,Tashiro, Masato,Sei, Yoshihisa,Yamaguchi, Kentaro,Kuzuhara, Takashi
scheme or table, p. 5379 - 5390 (2010/09/05)
Swine-origin influenza A virus has caused pandemics throughout the world and influenza A is regarded as a serious global health issue. Hence, novel drugs that will target these viruses are very desirable. Influenza A expresses an RNA polymerase essential for its transcription and replication which comprises PA, PB1, and PB2 subunits. We identified potential novel anti-influenza agents from a screen of 34 synthesized phenethylphenylphthalimide analogs derived from thalidomide (PPT analogs). For this screen we used a PA endonuclease inhibition assay, a PB2 pathogenicity-determinant domain-binding assay, and an anti-influenza A virus assay. Three PPT analogs, PPT-65, PPT-66, and PPT-67, were found to both inhibit PA endonuclease activity and retard the growth of influenza A, suggesting a correlation between their activities. PPT-28 was also found to inhibit the growth of influenza A. These four analogs have a 3,4-dihydroxyphenethyl group in common. We also discuss the possibility that 3,4-dihydroxyphenethyl group flexibility may play an important functional role in PA endonuclease inhibition. Another analog harboring a dimethoxyphenethyl group, PPT-62, showed PB2 pathogenicity-determinant domain-binding activity, but did not inhibit the growth of the virus. Our present results indicate the utility of the PA endonuclease assay in the screening of anti-influenza drugs and are therefore useful for future strategies to develop novel anti-influenza A drugs and for mapping the function of the influenza A RNA polymerase subunits.
Separation of α-glucosidase-inhibitory and liver X receptor-antagonistic activities of phenethylphenyl phthalimide analogs and generation of LXRα-selective antagonists
Motoshima, Kazunori,Noguchi-Yachide, Tomomi,Sugita, Kazuyuki,Hashimoto, Yuichi,Ishikawa, Minoru
experimental part, p. 5001 - 5014 (2009/12/24)
Liver X receptor (LXR) α/β dual agonists are candidate medicaments for the treatment of metabolic syndrome, because their biological actions include increasing cholesterol efflux mediated by LXRβ. However, their clinical application is currently limited by their enhancing effect on triglyceride (TG) synthesis mediated by LXRα. Combination of an LXRα-selective antagonist with an LXRα/β dual agonist may overcome this disadvantage. In the present work, structural development studies of phenethylphenyl phthalimide 9, which possesses LXRα/β dual-antagonistic activity and α-glucosidase-inhibitory activity, led to the LXRα-selective antagonist 23f. Specific α-glucosidase inhibitors were also obtained.
