N-benzoyl-(L)-α-aminosuberoyl-8-quinolinamide-ω-hydroxamic acid

• 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-benzoyl-(L)-α-aminosuberoyl-8-quinolinamide-ω-hydroxamic acid
• 英文别名: N-benzyloxycarbonyl-ω-tert-butyl-L-α-aminosuberoyl-8-quinolinamide；(S)-N-(8-(hydroxyamino)-1,8-dioxo-1-(quinolin-8-ylamino)octan-2-yl)benzamide；(2S)-2-benzamido-N'-hydroxy-N-quinolin-8-yloctanediamide
• 化学式: C₂₄H₂₆N₄O₄
• 分子量: 434.495
• InChiKey: SSUQSWVDYYVPHT-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  120
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (1S)-[6-hydroxycarbamoyl-1-(quinolin-8-ylcarbamoyl)-hexyl]-carbamic acid benzyl ester 在 5%-palladium/activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-benzoyl-(L)-α-aminosuberoyl-8-quinolinamide-ω-hydroxamic acid
  参考文献：
  名称：

  Derivatives of 1-amino-1-(hetero)arylaminocarbonyl-6-hydroxyaminocarbonylhexane useful in the treatment of tumors

  摘要：

  公开号：

  EP1231919B1

文献信息

• Aminosuberoyl hydroxamic acids (ASHAs): A potent new class of HDAC inhibitors
  作者：Sandro Belvedere、David J. Witter、Jiaming Yan、J. Paul Secrist、Victoria Richon、Thomas A. Miller

  DOI：10.1016/j.bmcl.2007.04.089

  日期：2007.7

  Histone deacetylase (HDAC) inhibitors that target Class I and Class II HDACs are currently in advanced clinical trials for the treatment of cancer. Vorinostat (Zolinza, SAHA) is a hydroxamic acid approved for the treatment of patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. As part of an on-going effort to better understand

  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。 。
• 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。
• Hydroxamic acid compounds and methods of use thereof
  申请人：Breslow Ronald

  公开号：US20070155785A1

  公开（公告）日：2007-07-05

  The present invention relates to a novel class of hydroxamic acid derivatives having at least two aryl containing groups, at least one of which is a quinolinyl, isoquinolinyl or benzyl moiety, linked to the hydroxamic acid group through a methylene chain. The hydroxamic acid compounds can be used to treat cancer, for example, brain cancer. The hydroxamic acid compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention are also useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

  本发明涉及一种新型的羟肟酸衍生物，其至少具有两个含芳基团的结构，其中至少一个是喹啉基团、异喹啉基团或苄基团，通过亚甲基链连接到羟肟酸基团上。这些羟肟酸化合物可用于治疗癌症，例如脑癌。这些羟肟酸化合物还可以抑制组蛋白去乙酰化酶，并适用于选择性诱导末期分化、阻止肿瘤细胞生长和/或凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物可用于治疗具有肿瘤细胞增殖特征的患者。该发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫、过敏和炎症性疾病，以及中枢神经系统（CNS）疾病的预防和/或治疗，例如神经退行性疾病。
• TREATMENT OF NEURODEGENERATIVE DISEASES AND CANCER OF THE BRAIN
  申请人：Sloan-Kettering Institute For Cancer Research

  公开号：EP1443928B1

  公开（公告）日：2011-07-27
• Histone Deacetylase Inhibitors for the Treatment of Ocular Neovascular or Edematous Disorders and Diseases
  申请人：Klimko Peter G.

  公开号：US20100048608A1

  公开（公告）日：2010-02-25

  Ophthalmic compositions containing HDAC inhibitors and their use for treating ocular neovascular or edematous diseases and disorders are disclosed.