N¹-hydroxy-N⁸-(5-phenyl-1,3,4-thiadiazol-2-yl)-1,8-octanediamide | 1338209-05-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N¹-hydroxy-N⁸-(5-phenyl-1,3,4-thiadiazol-2-yl)-1,8-octanediamide
• 英文别名: N¹-hydroxy-N⁸-(5-phenyl-1,3,4-thiadiazol-2-yl)octanediamide；N'-hydroxy-N-(5-phenyl-1,3,4-thiadiazol-2-yl)octanediamide
• CAS: 1338209-05-4
• 化学式: C₁₆H₂₀N₄O₃S
• 分子量: 348.426
• InChiKey: NULPLUOLABMUEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-5-苯基-1,3,4-噻二唑 在 盐酸羟胺 、 N,N'-羰基二咪唑 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.67h， 生成 N¹-hydroxy-N⁸-(5-phenyl-1,3,4-thiadiazol-2-yl)-1,8-octanediamide
  参考文献：
  名称：

  Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents

  摘要：

  Since the first histone deacetylase (HDAC) inhibitor (Zolinza®, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. A number of compounds in this series, for example, N(1)-hydroxy-N(8)-(5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5b), N(1)-hydroxy-N(8)-(5-(3-chlorophenyl-1,3,4-thiadiazol-2-yl)octandiamide (5c) and N(1)-hydroxy-N(8)-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5d), were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. Compounds 5b-d were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8.

  DOI：

  10.3109/14756366.2013.832238

文献信息

• 신규 페닐티아졸 기반 히드록삼산 및 이를 유효성분으로 포함하는 항암용 조성물
  申请人：Chungbuk National University Industry-Academic Cooperation Foundation 충북대학교 산학협력단(220040168226) BRN ▼301-82-16304

  公开号：KR101586045B1

  公开（公告）日：2016-01-15

  본 발명은 신규의 페닐티아졸 기반 히드록삼산 화합물 및 이를 유효성분으로 포함하는 항암용 조성물에 관한 것이다. 본 발명의 히드록삼산 화합물은 히스톤 탈아세틸화 효소(histone deacetylase, HDAC)의 억제 활성을 가지며, 다양한 암세포에서 세포독성을 나타내어 항암 효능을 발휘하므로, 강력한 항암제의 활성성분으로 개발될 수 있다.

  本发明涉及一种新型的苯并噻唑基础的羟基酸化合物以及包含其作为有效成分的抗癌组合物。本发明的羟基酸化合物具有组蛋白去乙酰化酶（HDAC）的抑制活性，在各种癌细胞中表现出细胞毒性，从而发挥抗癌作用，因此可以作为强效抗癌药物的活性成分开发。
• Design, synthesis and preliminary bioactivity studies of 1,3,4-thiadiazole hydroxamic acid derivatives as novel histone deacetylase inhibitors
  作者：Peng Guan、Feng’e Sun、Xuben Hou、Feng Wang、Fan Yi、Wenfang Xu、Hao Fang

  DOI：10.1016/j.bmc.2012.04.032

  日期：2012.6

  Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. In the present study, a series of 1,3,4-thiadiazole based hydroxamic acids were developed as potent HDAC inhibitors. Some of them showed good inhibitory activity in HDAC enzyme assay and potent growth inhibition in some tumor cell lines. Among them, compound 6i (IC50 = 0.089 mu M), exhibited better inhibitory effect compared with SAHA (IC50 = 0.15 mu M). (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents
  作者：Nguyen-Hai Nam、Tran Lan Huong、Do Thi Mai Dung、Phan Thi Phuong Dung、Dao Thi Kim Oanh、Sang Ho Park、Kyungrok Kim、Byung Woo Han、Jieun Yun、Jong Soon Kang、Youngsoo Kim、Sang-Bae Han

  DOI：10.3109/14756366.2013.832238

  日期：2014.10.1

  Since the first histone deacetylase (HDAC) inhibitor (Zolinza®, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. A number of compounds in this series, for example, N(1)-hydroxy-N(8)-(5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5b), N(1)-hydroxy-N(8)-(5-(3-chlorophenyl-1,3,4-thiadiazol-2-yl)octandiamide (5c) and N(1)-hydroxy-N(8)-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5d), were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. Compounds 5b-d were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8.