N-[(1S)-7-(hydroxyamino)-7-oxo-1-(phenylcarbamoyl)heptyl]-2-oxopyrrolidine-3-carboxamide | 1528755-51-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-[(1S)-7-(hydroxyamino)-7-oxo-1-(phenylcarbamoyl)heptyl]-2-oxopyrrolidine-3-carboxamide
• 英文别名: (2S)-N'-hydroxy-2-[(2-oxopyrrolidine-3-carbonyl)amino]-N-phenyloctanediamide
• CAS: 1528755-51-2
• 化学式: C₁₉H₂₆N₄O₅
• 分子量: 390.439
• InChiKey: OBQXNVXJMUPSRH-LOACHALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 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 N-甲基吗啉 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 palladium on activated charcoal 、 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 、 4-(4,6-二甲氧基三嗪-2-基)-4-甲基吗啉盐酸盐 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 48.0h， 生成 N-[(1S)-7-(hydroxyamino)-7-oxo-1-(phenylcarbamoyl)heptyl]-2-oxopyrrolidine-3-carboxamide
  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

• [EN] HYDROXAMATE DERIVATIVES BEARING AMIDE-LACTAMS AS POTENT HDAC INHIBITORS AND THEIR USES AS MEDICAMENTS<br/>[FR] DÉRIVÉS D'HYDROXAMATE PORTANT DES AMIDE-LACTAMES À TITRE DE PUISSANTS INHIBITEURS D'HDAC ET LEURS UTILISATIONS À TITRE DE MÉDICAMENTS
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2014122222A1

  公开（公告）日：2014-08-14

  The present invention relates to novel amide compounds of Formula (I), and their use as anti-tumoral and pro-apoptotic agents. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of HDAC is responsive, and the pharmaceutical composition containing such compounds.

  本发明涉及式(I)的新酰胺化合物，及其用作抗肿瘤和促凋亡剂的应用。该发明包括将此类化合物用于医学领域，与癌症以及其他抑制HDAC有响应的疾病的治疗相关，以及包含此类化合物的药物组合物。
• 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.