2-[3-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]phenyl]-N,N'-diphenylpropanediamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-[3-[(E)-3-(hydroxyamino)-3-oxoprop-1-enyl]phenyl]-N,N'-diphenylpropanediamide
• 化学式: C₂₄H₂₁N₃O₄
• 分子量: 415.4
• InChiKey: SQGNVWSNUGLNRK-CCEZHUSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  4

文献信息

• Methods of treating cancer with HDAC inhibitors
  申请人：——

  公开号：US20040127523A1

  公开（公告）日：2004-07-01

  The present invention relates to methods of treating cancers, e.g., lymphoma. More specifically, the present invention relates to methods of treating diffuse large B-cell lymphoma (DLBCL), by administration of pharmaceutical compositions comprising HDAC inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The oral formulations of the pharmaceutical compositions have favorable pharmacokinetic profiles such as high bioavailability and surprisingly give rise to high blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

  本发明涉及治疗癌症的方法，例如淋巴瘤。更具体地说，本发明涉及通过给予含有HDAC抑制剂的药物组合物，例如suberoylanilide羟肟酸（SAHA），治疗弥漫性大B细胞淋巴瘤（DLBCL）的方法。这些药物组合物的口服制剂具有良好的药代动力学特性，例如高生物利用度，并且令人惊讶地在延长的时间内产生高水平的活性化合物血浓度。本发明还提供了这些药物组合物的安全、每日剂量方案，易于遵循，并在体内产生治疗有效量的HDAC抑制剂。
• Polymorphs of suberoylanilide hydroxamic acid
  申请人：Miller Thomas A.

  公开号：US20080194692A1

  公开（公告）日：2008-08-14

  The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo. The present invention also provides a novel Form I polymorph of SAHA, characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well a unique crystalline structure.

  本发明提供了通过给予含有强效HDAC抑制剂的药物组合物来选择性诱导肿瘤细胞的终端分化、细胞生长停滞和/或凋亡，并/或抑制组蛋白去乙酰化酶（HDAC）的方法。本发明中药物组合物中活性化合物的口服生物利用度出乎意料地高。此外，该药物组合物意外地产生了活性化合物的高、治疗有效的血液水平，持续时间较长。本发明还提供了一种安全的、每日剂量的服用方案，易于遵循，并在体内产生治疗有效量的HDAC抑制剂。本发明还提供了一种SAHA的Form I多晶形态，其具有独特的X射线衍射图案和差示扫描量热法（DSC）谱图，以及独特的晶体结构。
• 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。
• Methods of inducing terminal differentiation
  申请人：Richon M. Victoria

  公开号：US20080114069A1

  公开（公告）日：2008-05-15

  The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

  本发明提供了通过给予含有高效的HDAC抑制剂的药物组合物，选择性诱导肿瘤细胞的末端分化、细胞生长停滞和/或凋亡，并/或抑制组蛋白去乙酰化酶（HDAC）的方法。该药物组合物中活性化合物的口服生物利用度令人惊讶地高。此外，该药物组合物意外地在延长时间内产生高剂量的治疗有效的活性化合物血浆水平。本发明还提供了一种安全的、易于遵循的这些药物组合物的每日剂量方案，并在体内产生治疗有效的HDAC抑制剂量。
• Combination methods of treating cancer
  申请人：Bacopoulos G. Nicholas

  公开号：US20070190022A1

  公开（公告）日：2007-08-16

  The present invention relates to a method of treating cancer in a subject in need thereof, by administering to a subject in need thereof a first amount of a histone deacetylase (HDAC) inhibitor or a pharmaceutically acceptable salt or hydrate thereof, in a first treatment procedure, and a second amount of an anti-cancer agent in a second treatment procedure. The first and second amounts together comprise a therapeutically effective amount. The effect of the HDAC inhibitor and the anti-cancer agent may be additive or synergistic.

  本发明涉及一种治疗癌症的方法，通过在第一次治疗过程中向需要治疗的对象给予一定量的组蛋白去乙酰化酶（HDAC）抑制剂或其药学上可接受的盐或水合物，以及在第二次治疗过程中给予一定量的抗癌剂。第一次和第二次给予的药量加起来构成治疗上有效的药量。HDAC抑制剂和抗癌剂的作用可能是加成或协同的。