ST8087AA1 | 1528755-81-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ST8087AA1
• 英文别名: (2S)-N'-hydroxy-2-[[(2S)-4-oxoazetidine-2-carbonyl]amino]-N-phenyloctanediamide
• CAS: 1528755-81-8
• 化学式: C₁₈H₂₄N₄O₅
• 分子量: 376.412
• InChiKey: GHCWLYKERZOPPW-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  137
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (S)-2-((叔丁氧羰基)氨基)庚-6-烯酸 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 palladium on activated charcoal 、 10 wt% Pd(OH)2 on carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 1,2-二氯乙烷 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 24.0h， 生成 ST8087AA1
  参考文献：
  名称：

  Lactam based 7-amino suberoylamide hydroxamic acids as potent HDAC inhibitors

  摘要：

  A series of SAHA-like molecules were prepared introducing different lactam-carboxyamides in position 7 of the suberoylanilide skeleton. The activity against different HDAC isoforms was tested and the data compared with the corresponding linear products, without substituent in position 7. In general, this modification provided an effective reinforcement of in vitro activity. While the lactam size or the CO/NH group orientation did not strongly influence the inhibition, the contemporary modification of the suberoylamide fragment gave vary active variants in the lactam series, with compound 28 (ST8078AA1) that showed IC50 values between 2 and 10 nM against all Class I HDAC isoforms, demonstrating it to be a large spectrum pan-inhibitor. This strong affinity with HDAC was also confirmed by the value of IC50 = 0.5 mu M against H460 cells, ranking 28 as one of the most potent HDAC inhibitors described so far. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.11.072

文献信息

• Lactam based 7-amino suberoylamide hydroxamic acids as potent HDAC inhibitors
  作者：Maurizio Taddei、Elena Cini、Luca Giannotti、Giuseppe Giannini、Gianfranco Battistuzzi、Davide Vignola、Loredana Vesci、Walter Cabri

  DOI：10.1016/j.bmcl.2013.11.072

  日期：2014.1

  A series of SAHA-like molecules were prepared introducing different lactam-carboxyamides in position 7 of the suberoylanilide skeleton. The activity against different HDAC isoforms was tested and the data compared with the corresponding linear products, without substituent in position 7. In general, this modification provided an effective reinforcement of in vitro activity. While the lactam size or the CO/NH group orientation did not strongly influence the inhibition, the contemporary modification of the suberoylamide fragment gave vary active variants in the lactam series, with compound 28 (ST8078AA1) that showed IC50 values between 2 and 10 nM against all Class I HDAC isoforms, demonstrating it to be a large spectrum pan-inhibitor. This strong affinity with HDAC was also confirmed by the value of IC50 = 0.5 mu M against H460 cells, ranking 28 as one of the most potent HDAC inhibitors described so far. (C) 2013 Elsevier Ltd. All rights reserved.
• Hydroxamic acid based histone deacetylase inhibitors with confirmed activity against the malaria parasite
  作者：Giuseppe Giannini、Gianfranco Battistuzzi、Davide Vignola

  DOI：10.1016/j.bmcl.2014.12.051

  日期：2015.2

  Recent studies have highlighted a key role in regulating gene transcription, in both eukaryotes and prokaryotes, by enzymes that control the acetylation and deacetylation of histones. In particular, inhibitors of histone deacetylases (HDAC-Is) have been shown effective in controlling the development of many parasites, such as the plasmodium of malaria. Here we report the results of a study aimed at evaluating antiparasitic effect of two classes of HDAC-Is bearing different zinc binding group (hydroxamic acid vs thiol). The study showed that only the hydroxamic acid based HDAC inhibitors were active, with Plasmodium falciparum being the most sensitive parasite, having from low double-digit to single-digit nanomolar range in vitro activities. Among three derivatives evaluated also in vivo, ST8086AA1 (8) effectively inhibited 88% of the development of Plasmodium falciparum. (C) 2014 Elsevier Ltd. All rights reserved.