کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1357523 | 1500520 | 2016 | 6 صفحه PDF | دانلود رایگان |
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.
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Journal: Bioorganic & Medicinal Chemistry - Volume 24, Issue 18, 15 September 2016, Pages 4318–4323