N-phenyl-7-sulfanylheptanamide | 728890-39-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-phenyl-7-sulfanylheptanamide
• 英文别名: 7-Mercapto-heptanoic acid phenylamide
• CAS: 728890-39-9
• 化学式: C₁₃H₁₉NOS
• 分子量: 237.366
• InChiKey: CFKBMXXDXYFDET-UHFFFAOYSA-N

物化性质

• 熔点：
  88-89 °C
• 沸点：
  427.4±28.0 °C(Predicted)
• 密度：
  1.083±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  30.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-phenyl-7-sulfanylheptanamide 在 sodium hydroxide 、 sodium ethanolate 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Design and synthesis of non-hydroxamate histone deacetylase inhibitors: identification of a selective histone acetylating agent

  摘要：

  A series of suberoylanilide hydroxamic acid (SAHA)-based non-hydroxamates was designed, synthesized, and evaluated for their histone deacetylase (HDAC) inhibitory activity. Among these, methyl sulfoxide 15 inhibited HDACs in enzyme assays and caused hyperacetylation of histone H4 while not inducing the accumulation of acetylated alpha-tubulin in HCT116 cells. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.002
• 作为产物：
  描述：

  7-溴庚酸 在 sodium hydroxide 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-phenyl-7-sulfanylheptanamide
  参考文献：
  名称：

  人组蛋白脱乙酰基酶的新型抑制剂：基于SAHA的非异羟肟酸酯的设计，合成，酶抑制和癌细胞生长抑制。

  摘要：

  为了找到新型的非异羟肟酸酯组蛋白脱乙酰基酶（HDAC）抑制剂，设计并合成了以亚磺酰苯胺异羟肟酸（SAHA）为模型的一系列化合物。在该系列中，发现化合物7（其中SAHA的异羟肟酸被硫醇替代）与SAHA一样有效，该系列的优化导致鉴定出比SAHA更有效的HDAC抑制剂。在癌细胞生长抑制测定中，S-异丁酰基衍生物51显示出强活性，并且其效力与SAHA相当。通过Western印迹分析证实癌细胞生长抑制活性是组蛋白过度乙酰化和随后诱导p21（WAF1 / CIP1）的结果。

  DOI：

  10.1021/jm049207j

文献信息

• [EN] HDAC INHIBITORS-BASED ANTIBODY DRUG CONJUGATES (ADCs) AND USE IN THERAPY<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENTS (CAM) À BASE D'INHIBITEURS D'HDAC ET LEUR UTILISATION DANS LA THÉRAPIE
  申请人：ALFASIGMA SPA

  公开号：WO2018178060A1

  公开（公告）日：2018-10-04

  The present invention relates to novel Histone Deacetylase Inhibitors (HDACi)- based antibody drug conjugates particularly with antibodies directed to ErbB1, ErbB2 and ErbB3 receptors, pharmaceutical compositions comprising said antibodies as well as to their use in the treatment of cancer or tumor and other diseases where a modulation of one or more histone deacetylase isoforms can be effective for therapeutic interventions.

  本发明涉及一种新型组蛋白去乙酰化酶抑制剂（HDACi）基于抗体药物偶联物，特别是与针对ErbB1、ErbB2和ErbB3受体的抗体结合的抗体药物偶联物，包括所述抗体的制药组合物，以及它们在癌症或肿瘤以及其他需要调节一个或多个组蛋白去乙酰化酶亚型以实现治疗干预的疾病的治疗中的用途。
• [EN] NEW THIO DERIVATIVES BEARING LACTAMS AS POTENT HDAC INHIBITORS AND THEIR USES AS MEDICAMENTS<br/>[FR] NOUVEAUX DÉRIVÉS THIO PORTANT DES LACTAMES EN TANT QU'INHIBITEURS PUISSANTS D'HDAC, ET LEURS UTILISATIONS EN TANT QUE MÉDICAMENTS
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2013041480A1

  公开（公告）日：2013-03-28

  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.

  本发明涉及一种新型酰胺化合物（式I），以及其作为抗肿瘤和促凋亡剂的用途。该发明包括在医学上使用这些化合物，涉及癌症疾病以及其他需要抑制HDAC的疾病，以及含有这些化合物的药物组合物。
• NEW THIO DERIVATIVES BEARING LACTAMS AS POTENT HDAC INHIBITORS AND THEIR USES AS MEDICAMENTS
  申请人：SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.

  公开号：US20140200205A1

  公开（公告）日：2014-07-17

  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）的新型酰胺化合物，以及它们作为抗肿瘤和促凋亡剂的用途。该发明涉及这些化合物在医学上的应用，与癌症以及其他需要抑制HDAC的疾病有关，以及含有这些化合物的药物组合物。
• HISTONE DEACETYLASE INHIBITORS-BASED ANTIBODY DRUG CONJUGATES (ADCS) AND USE IN THERAPY
  申请人：Alfasigma S.p.A.

  公开号：EP3381474A1

  公开（公告）日：2018-10-03

  The present invention relates to novel Histone Deacetylase Inhibitors (HDACi)-based antibody drug conjugates with antibodies directed against a histone deacetylase inhibitor or against a receptor internalized by tumor cells to release a histone deacetylase inhibitor, particularly with antibodies directed to ErbB1, ErbB2 and ErbB3 receptors, pharmaceutical compositions comprising said antibodies as well as to their use in the treatment of cancer or tumor and other diseases where a modulation of one or more histone deacetylase isoforms can be effective for therapeutic interventions.

  本发明涉及基于新型组蛋白去乙酰化酶抑制剂（HDACi）的抗体药物共轭物，其抗体针对组蛋白去乙酰化酶抑制剂或针对肿瘤细胞内化释放组蛋白去乙酰化酶抑制剂的受体，特别是针对ErbB1、ErbB2和ErbB3受体的抗体、ErbB1、ErbB2 和 ErbB3 受体的抗体、包含上述抗体的药物组合物，以及它们在治疗癌症或肿瘤和其他疾病中的用途，在这些疾病中，调节一种或多种组蛋白去乙酰化酶同工酶可有效地进行治疗干预。
• ST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors
  作者：Giuseppe Giannini、Loredana Vesci、Gianfranco Battistuzzi、Davide Vignola、Ferdinando M. Milazzo、Mario Berardino Guglielmi、Marcella Barbarino、Mosè Santaniello、Nicola Fantò、Marco Mor、Silvia Rivara、Daniele Pala、Maurizio Taddei、Claudio Pisano、Walter Cabri

  DOI：10.1021/jm5008209

  日期：2014.10.23

  A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ?-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ?-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.