Steric structure–activity relationship of cyproheptadine derivatives as inhibitors of histone methyltransferase Set7/9
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説明
Set7/9 is a histone lysine methyltransferase, but it is also thought to be involved in a wide variety of pathophysiological functions. We previously identified cyproheptadine, which has a characteristic butterfly-like molecular conformation with bent tricyclic dibenzosuberene and chair-form N-methylpiperidine moieties, as a Set7/9 inhibitor. In this work, we synthesized several derivatives in order to examine the steric structure-inhibitory activity relationship. We found that even a small change of molecular shape due to reduction or replacement of the 10,11-olefinic bond of the tricyclic ring generally resulted in a drastic decrease of the inhibitory activity. Our results should be useful not only for development of more potent and selective inhibitors, but also for the construction of novel inhibitor scaffolds.
収録刊行物
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- Bioorganic & Medicinal Chemistry
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Bioorganic & Medicinal Chemistry 24 (18), 4318-4323, 2016-09
Elsevier BV