Methyl 8-(hydroxyamino)-8-oxooctanoate | 149647-87-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Methyl 8-(hydroxyamino)-8-oxooctanoate
• CAS: 149647-87-0
• 化学式: C₉H₁₇NO₄
• 分子量: 203.238
• InChiKey: WMMXJCQWLLQMBW-UHFFFAOYSA-N

物化性质

• 密度：
  1.104±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 8-(hydroxyamino)-8-oxooctanoate 在 羟胺 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 生成 软木肟酸
  参考文献：
  名称：

  Modified Cap Group Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivatives Reveal Improved Selective Antileukemic Activity

  摘要：

  A series of SAHA cap derivatives was designed and prepared in good-to-excellent yields that varied from 49% to 95%. These derivatives were evaluated for their antiproliferative activity in several human cancer cell lines. Antiproliferative activity was observed for concentrations varying from 0.12 to > 100 mu M, and a molecular modeling approach of selected SAHA derivatives, based on available structural information of human HDAC8 in complex with SAHA, was performed. Strikingly, two compounds displayed up to 10-fold improved antileukemic activity with respect to SAHA; however, these compounds displayed antiproliferative activity similar to SAHA when assayed against solid tumor-derived cell lines. A 10-fold improvement in the leukemic vs peripheral blood mononuclear cell therapeutic ratio, with no evident in vivo toxicity toward blood cells, was also observed. The herein-described compounds and method of synthesis will provide invaluable tools to investigate the molecular mechanism responsible for the reported selectively improved antileukemic activity.

  DOI：

  10.1021/jm901358y
• 作为产物：
  描述：

  辛二酸单甲酯 、 羟胺 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 二异丙胺 作用下， 以 二氯甲烷 为溶剂， 生成 Methyl 8-(hydroxyamino)-8-oxooctanoate
  参考文献：
  名称：

  Modified Cap Group Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivatives Reveal Improved Selective Antileukemic Activity

  摘要：

  A series of SAHA cap derivatives was designed and prepared in good-to-excellent yields that varied from 49% to 95%. These derivatives were evaluated for their antiproliferative activity in several human cancer cell lines. Antiproliferative activity was observed for concentrations varying from 0.12 to > 100 mu M, and a molecular modeling approach of selected SAHA derivatives, based on available structural information of human HDAC8 in complex with SAHA, was performed. Strikingly, two compounds displayed up to 10-fold improved antileukemic activity with respect to SAHA; however, these compounds displayed antiproliferative activity similar to SAHA when assayed against solid tumor-derived cell lines. A 10-fold improvement in the leukemic vs peripheral blood mononuclear cell therapeutic ratio, with no evident in vivo toxicity toward blood cells, was also observed. The herein-described compounds and method of synthesis will provide invaluable tools to investigate the molecular mechanism responsible for the reported selectively improved antileukemic activity.

  DOI：

  10.1021/jm901358y

文献信息

• [EN] CARBOLINE AND BETACARBOLINE DERIVATIVES FOR USE AS HDAC ENZYME INHIBITORS<br/>[FR] DERIVES DE CARBOLINE ET DE BETACARBOLINE INHIBITEURS DE L'ENZYME HDAC
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2004113336A1

  公开（公告）日：2004-12-29

  Compounds of formula (IA) and (IB) are inhibitors of histone deacetylase activity and useful for the treatment of, inter alia, cancers: wherein fused rings A1 and A2 are optionally substituted; linker radical R1 represents a radical of formula

  式（IA）和（IB）的化合物是组蛋白去乙酰化酶活性的抑制剂，用于治疗癌症等疾病：其中融合的环A1和A2可以选择性地被取代；连接基团R1代表一个公式的基团。
• TREATMENT OF SOLID TUMORS
  申请人：President and Fellows of Harvard College

  公开号：EP3354265A1

  公开（公告）日：2018-08-01

  The invention relates to methods of treating protein degradation disorders, such as cellular proliferative disorders (e.g., cancer). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating solid tumors. New HDAC/TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.

  本发明涉及治疗蛋白质降解紊乱的方法，如细胞增殖紊乱（如癌症）。本发明提供了使用侵袭酶体抑制剂或侵袭酶体抑制剂和蛋白酶体抑制剂组合治疗这些疾病的方法和药物组合物。本发明还涉及治疗实体瘤的方法和药物组合物。本发明还提供了新的HDAC/TDAC抑制剂和侵袭体抑制剂以及制备这些化合物的合成方法。
• Treatment of protein degradation disorders
  申请人：President and Fellows of Harvard College

  公开号：US10172905B1

  公开（公告）日：2019-01-08

  The invention relates to methods of treating protein degradation disorders, such cellular proliferative disorders (e.g., cancer) and protein deposition disorders (e.g., neurodegenerative disorders). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating multiple myeloma. New HDAC/TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.

  本发明涉及治疗蛋白质降解紊乱的方法，如细胞增殖紊乱（如癌症）和蛋白质沉积紊乱（如神经退行性疾病）。本发明提供了使用侵袭酶体抑制剂或侵袭酶体抑制剂和蛋白酶体抑制剂组合治疗这些疾病的方法和药物组合物。本发明还涉及治疗多发性骨髓瘤的方法和药物组合物。本发明还提供了新的 HDAC/TDAC 抑制剂和侵袭体抑制剂以及制备这些化合物的合成方法。
• COMPOUNDS AND METHODS FOR IMPROVING IMPAIRED ENDOGENOUS FIBRINOLYSIS USING HISTONE DEACETYLASE INHIBITORS
  申请人：Cereno Scientific AB

  公开号：US20210060014A1

  公开（公告）日：2021-03-04

  There is provided a compound which is a histone deacetylase (HDAC) inhibitor, or a pharmaceutically acceptable ester, amide, solvate or salt thereof, for use in: (I) treating or preventing a pathological condition associated with excess fibrin deposition and/or thrombus formation; and/or (II) potentiating the degradation of fibrin deposits and preventing such deposits associated with pathological conditions or which may lead to such conditions, wherein the HDAC inhibitor, and the dose thereof, is as described in the description. There is also provided valproic acid, or a pharmaceutically acceptable salt thereof, for use in improving or normalizing endogenous fibrinolysis impaired by local or systemic inflammation.
• US8999289B2
  申请人：——

  公开号：US8999289B2

  公开（公告）日：2015-04-07