Nexturastat A | 1403783-31-2

• 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: Nexturastat A
• 英文别名: 4-((1-butyl-3-phenylureido)methyl)-N-hydroxybenzamide；nexturastat；4-[[butyl(phenylcarbamoyl)amino]methyl]-N-hydroxybenzamide
• CAS: 1403783-31-2
• 化学式: C₁₉H₂₃N₃O₃
• 分子量: 341.41
• InChiKey: JZWXMCPARMXZQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  81.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  methyl 4-((butylamino)methyl)benzoate 在 羟胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 16.5h， 生成 Nexturastat A
  参考文献：
  名称：

  Selective Histone Deacetylase 6 Inhibitors Bearing Substituted Urea Linkers Inhibit Melanoma Cell Growth

  摘要：

  The incidence of malignant melanoma has dramatically increased in recent years thus requiring the need for improved therapeutic strategies. In our efforts to design selective histone deactylase inhibitors (HDACI), we discovered that the aryl urea 1 is a modestly potent yet nonselective inhibitor. Structure-activity relationship studies revealed that adding substituents to the nitrogen atom of the urea so as to generate compounds bearing a branched linker group results in increased potency and selectivity for HDAC6. Compound 5g shows low nanomolar inhibitory potency against HDAC6 and a selectivity of similar to 600-fold relative to the inhibition of HDACI. These HDACIs were evaluated for their ability to inhibit the growth of B16 melanoma cells with the most potent and selective HDAC6I being found to decrease tumor cell growth. To the best of our knowledge, this work constitutes the first report of HDAC6-selective inhibitors that possess antiproliferative effects against melanoma cells.

  DOI：

  10.1021/jm301098e

文献信息

• [EN] SELECTIVE HISTONE DEACTYLASE 6 INHIBITORS<br/>[FR] INHIBITEURS SÉLECTIFS D'HISTONE DÉSACÉTYLASE 6
  申请人：H LEE MOFFITT CANCER CT & RES

  公开号：WO2013134467A1

  公开（公告）日：2013-09-12

  Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

  披露了具有化学式（I）的选择性组蛋白去乙酰化酶抑制剂（HDACi）。还披露了制备和使用这些抑制剂用于治疗癌症，特别是黑色素瘤的方法。
• SELECTIVE HISTONE DEACTYLASE 6 INHIBITORS
  申请人：H.LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US20150056213A1

  公开（公告）日：2015-02-26

  Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

  本发明涉及具有式(I)的选择性组蛋白去乙酰化酶抑制剂（HDACi）。本发明还公开了制备和使用这些抑制剂治疗癌症，特别是黑色素瘤的方法。
• Selective histone deactylase 6 inhibitors
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US10227295B2

  公开（公告）日：2019-03-12

  Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula I. Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

  所公开的是具有式 I 的选择性组蛋白去乙酰化酶抑制剂（HDACi）。还公开了制造和使用这些抑制剂治疗癌症，特别是黑色素瘤的方法。
• Synthesis of small molecule histone deacetylase 6 degraders, compounds formed thereby, and pharmaceutical compositions containing them
  申请人：Wisconsin Alumni Research Foundation

  公开号：US11059815B2

  公开（公告）日：2021-07-13

  Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.

  组蛋白去乙酰化酶（"HDAC"）选择性抑制剂，共价键合到与 E3 泛素配体共价键合的连接体上，及其盐类；含有它们的药物组合物；使用该组合物抑制哺乳动物（包括人类）肿瘤细胞生长的方法。
• Compositions and Methods for the Treatment and Prevention of Cancer
  申请人：California State University Northridge

  公开号：US20190216751A1

  公开（公告）日：2019-07-18

  A method of treating a subject with cancer is provided. The method includes administering to a subject in need thereof an effective amount of a pharmaceutical composition that includes inhibitors of HDAC6 and/or sirtuins and an inhibitor of deoxyhypusine synthase (DHPS). Methods also include treating a subject with cancer by administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising at least one inhibitor of sirtuin and at least one inhibitor of histone deacetylase six (HDAC6); at least one inhibitor of sirtuin or at least one inhibitor of histone deacetylase six (HDAC6), or a combination thereof. Additional methods include treating a subject with cancer by administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising at least one inhibitor of sirtuin, an inhibitor of deoxyhypusine synthase (DHPS), and at least one inhibitor of histone deacetylase six (HDAC6); at least one inhibitor of sirtuin, an inhibitor of deoxyhypusine synthase (DHPS), or at least one inhibitor of histone deacetylase six (HDAC6), or a combination thereof.