(S)-methyl 7-(tert-butoxycarbonylamino)-8-oxo-8-(phenylamino)octanoate | 329966-94-1

• 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: (S)-methyl 7-(tert-butoxycarbonylamino)-8-oxo-8-(phenylamino)octanoate
• 英文别名: N-boc-ω-methyl-(L)-α-aminosuberate；boc-asu(OMe)-NHPh；(7S)-tert-butoxycarbonylamino-7-phenylcarbamoyl-heptanoic acid methyl ester；methyl (7S)-8-anilino-7-[(2-methylpropan-2-yl)oxycarbonylamino]-8-oxooctanoate
• CAS: 329966-94-1
• 化学式: C₂₀H₃₀N₂O₅
• 分子量: 378.469
• InChiKey: RKTDOZTUWTWCDD-INIZCTEOSA-N

物化性质

• 沸点：
  548.3±45.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-methyl 7-(tert-butoxycarbonylamino)-8-oxo-8-(phenylamino)octanoate 在 N-甲基吗啉 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  氨基亚Suberoyl异羟肟酸（ASHA）：一种新型的强效HDAC抑制剂。

  摘要：

  针对I类和II类HDAC的组蛋白脱乙酰基酶（HDAC）抑制剂目前正在用于癌症治疗的高级临床试验中。Vorinostat（Zolinza，SAHA）是一种异羟肟酸，已获批准用于治疗患有T型皮肤淋巴瘤的皮肤性T细胞淋巴瘤的患者，这些患者在两种全身疗法中或之后均患有进行性，持续性或复发性疾病。为了更好地了解HDAC酶/抑制剂相互作用的性质并设计高效HDAC抑制剂，我们正在进行的工作之一是在本文中报告了伏立诺司他衍生的一系列基于底物的HDAC抑制剂的设计，合成和HDAC抑制活性。 。

  DOI：

  10.1016/j.bmcl.2007.04.089
• 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 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、1.0 MPa 条件下， 反应 24.0h， 生成 (S)-methyl 7-(tert-butoxycarbonylamino)-8-oxo-8-(phenylamino)octanoate
  参考文献：
  名称：

  Hydroxamic acid based histone deacetylase inhibitors with confirmed activity against the malaria parasite

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2014.12.051

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。
• [EN] HISTONE DEACETYLASE INHIBITORS<br/>[FR] INHIBITEURS DE L'HISTONE DÉSACÉTYLASE
  申请人：MERCK & CO INC

  公开号：WO2006017216A1

  公开（公告）日：2006-02-16

  This invention relates to hydroxamic acid derivatives having a urea linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.

  这项发明涉及具有脲键的羟羟基脂肪酸衍生物，这些衍生物是组蛋白去乙酰化酶（HDAC）的抑制剂，可用于预防和/或治疗细胞增殖性疾病，例如癌症、自身免疫、过敏和炎症性疾病，中枢神经系统（CNS）疾病如神经退行性疾病，以及预防和/或治疗再狭窄。
• [EN] HISTONE DEACETYLASE INHIBITORS<br/>[FR] INHIBITEURS D'HISTONE DEACETYLASE
  申请人：MERCK & CO INC

  公开号：WO2006026260A1

  公开（公告）日：2006-03-09

  This invention relates to hydroxamic acid derivatives having a carbamate linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.

  本发明涉及具有氨基甲酸酯连接的羟肟酸衍生物，它们是组蛋白去乙酰化酶（HDAC）的抑制剂，并且在细胞增殖性疾病的预防和/或治疗中有用，例如癌症，自身免疫，过敏和炎症性疾病，中枢神经系统（CNS）疾病，如神经退行性疾病，并且在防止和/或治疗再狭窄方面有用。
• Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof
  申请人：Breslow Ronald

  公开号：US20070010536A1

  公开（公告）日：2007-01-11

  The present invention provides the compound having the formula: wherein each of R 1 and R 2 is, substituted or unsubstituted, aryl, cycloalkyl, cycloalkylamino, naphtha, pyridineamino, piperidino, t-butyl, aryloxy, arylalkyloxy, or pyridine group; wherein A is an amido moiety, —O—, —S—, —NH—, or —CH 2 —; and wherein n is an integer from 3 to 8. The present invention also provides a method of selectively inducing growth arrest, terminal differentiation and/or apoptosis of neoplastic cells and thereby inhibiting proliferation of such cells. Moreover, the present invention provides a method of treating a patient having a tumor characterized by proliferation of neoplastic cells. Lastly, the present invention provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically acceptable amount of the compound above.

  本发明提供了具有以下式子的化合物：其中R1和R2分别为取代或未取代的芳基、环烷基、环烷基氨基、萘基、吡啶氨基、哌啶基、叔丁基、芳氧基、芳基烷氧基或吡啶基；其中A为酰胺基、-O-、-S-、-NH-或-CH2-；n为3到8的整数。本发明还提供了一种选择性诱导肿瘤细胞生长停滞、终末分化和/或凋亡的方法，从而抑制这些细胞的增殖。此外，本发明还提供了一种治疗具有肿瘤细胞增殖特征的患者的方法。最后，本发明提供了一种包括药学上可接受的载体和上述化合物的治疗上可接受的剂量的药物组合物。
• 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.