NCH-31 | 728890-52-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: NCH-31
• 英文别名: 7-mercapto-N-(4-phenyl-2-thiazolyl)heptanamide；N-(4-phenyl-1,3-thiazol-2-yl)-7-sulfanylheptanamide
• CAS: 728890-52-6
• 化学式: C₁₆H₂₀N₂OS₂
• 分子量: 320.48
• InChiKey: LUXAHBUKMVESIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-苄基丙酸 、 NCH-31 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以63%的产率得到S-7-oxo-7-(4-phenylthiazol-2-ylamino)heptyl 2-methyl-3-phenylpropanethioate
  参考文献：
  名称：

  Identification of a potent and stable antiproliferative agent by the prodrug formation of a thiolate histone deacetylase inhibitor

  摘要：

  To identify prodrugs of a thiolate histone deacetylase inhibitor NCH-31 that show potent antiproliferative activity and are stable in human plasma, we synthesized several candidate prodrugs of NCH-31. Among these compounds, S-2-methyl-3-phenylpropanoyl compound 2 showed more potent antiproliferative activity and higher stability in human plasma than S-isobutyryl compound NCH-51. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.12.117
• 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 2.0h， 生成 NCH-31
  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] NEW COMPOUNDS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] NOUVEAUX COMPOSÉS POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2022087456A1

  公开（公告）日：2022-04-28

  Disclosed herein are novel drugs useful in treating Alzheimer's Disease and methods of use.

  本文披露了一种在治疗阿尔茨海默病方面有用的新型药物以及使用方法。
• Design, synthesis, and biological activity of folate receptor-targeted prodrugs of thiolate histone deacetylase inhibitors
  作者：Takayoshi Suzuki、Shinya Hisakawa、Yukihiro Itoh、Nobuaki Suzuki、Katsumasa Takahashi、Masatoshi Kawahata、Kentaro Yamaguchi、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1016/j.bmcl.2007.05.040

  日期：2007.8

  Aiming to develop selective anticancer drugs, we designed and synthesized three disulfides bearing a folic acid moiety as candidate folate receptor (FR)-targeted prodrugs of thiolate histone deacetylase inhibitors. Among them, compound 1 displayed growth-inhibitory activity toward folate receptor-positive MCF-7 breast cancer cells. The activity of I was significantly reduced by free folic acid, suggesting that cellular uptake of I is mediated by FR. (c) 2007 Elsevier Ltd. All rights reserved.
• Thiol-based SAHA analogues as potent histone deacetylase inhibitors
  作者：Takayoshi Suzuki、Akiyasu Kouketsu、Azusa Matsuura、Arihiro Kohara、Shin-ichi Ninomiya、Kohfuku Kohda、Naoki Miyata

  DOI：10.1016/j.bmcl.2004.03.063

  日期：2004.6

  In order to find novel nonhydroxamate histone deacetylase (HDAC) inhibitors, a series of thiol-based compounds modeled after suberoylanilide hydroxamic acid (SAHA) was synthesized, and their inhibitory effect on HDACs was evaluated. Compound 6, in which the hydroxamic acid of SAHA was replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. (C) 2004 Elsevier Ltd. All rights reserved.
• Novel Inhibitors of Human Histone Deacetylases:  Design, Synthesis, Enzyme Inhibition, and Cancer Cell Growth Inhibition of SAHA-Based Non-hydroxamates
  作者：Takayoshi Suzuki、Yuki Nagano、Akiyasu Kouketsu、Azusa Matsuura、Sakiko Maruyama、Mineko Kurotaki、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1021/jm049207j

  日期：2005.2.1

  To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer

  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。
• Identification of a potent and stable antiproliferative agent by the prodrug formation of a thiolate histone deacetylase inhibitor
  作者：Takayoshi Suzuki、Shinya Hisakawa、Yukihiro Itoh、Sakiko Maruyama、Mineko Kurotaki、Hidehiko Nakagawa、Naoki Miyata

  DOI：10.1016/j.bmcl.2006.12.117

  日期：2007.3

  To identify prodrugs of a thiolate histone deacetylase inhibitor NCH-31 that show potent antiproliferative activity and are stable in human plasma, we synthesized several candidate prodrugs of NCH-31. Among these compounds, S-2-methyl-3-phenylpropanoyl compound 2 showed more potent antiproliferative activity and higher stability in human plasma than S-isobutyryl compound NCH-51. (c) 2007 Elsevier Ltd. All rights reserved.