N-hydroxy-5-(4-pent-4-enamidobenzoyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide | 1391634-34-6

• 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: N-hydroxy-5-(4-pent-4-enamidobenzoyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide
• 英文别名: N-hydroxy-5-[4-(pent-4-enoylamino)benzoyl]-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide
• CAS: 1391634-34-6
• 化学式: C₁₉H₂₀N₄O₄S
• 分子量: 400.458
• InChiKey: OWHBIYPVUQYBPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-BOC-4-氨基苯甲酸 在 盐酸羟胺 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.5h， 生成 N-hydroxy-5-(4-pent-4-enamidobenzoyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide
  参考文献：
  名称：

  CCLab—a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design

  摘要：

  The introduction of the multi-objective optimization has dramatically changed the virtual combinatorial library design, which can consider many objectives simultaneously, such as synthesis cost and drug-likeness, thus may increase positive rates of biological active compounds. Here we described a software called CCLab (Combinatorial Chemistry Laboratory) for combinatorial library design based on the multi-objective genetic algorithm. Tests of the convergence ability and the ratio to re-take the building blocks in the reference library were conducted to assess the software in silico, and then it was applied to a real case of designing a 5 x 6 HDAC inhibitor library. Sixteen compounds in the resulted library were synthesized, and the histone deactetylase (HDAC) enzymatic assays proved that 14 compounds showed inhibitory ratios more than 50% against tested 3 HDAC enzymes at concentration of 20 mu g/mL, with IC50 values of 3 compounds comparable to SAHA. These results demonstrated that the CCLab software could enhance the hit rates of the designed library and would be beneficial for medicinal chemists to design focused library in drug development (the software can be downloaded at: http://202.127.30.184:8080/drugdesign.html). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.123

文献信息

• CCLab—a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design
  作者：Guanghua Fang、Mengzhu Xue、Mingbo Su、Dingyu Hu、Yanlian Li、Bing Xiong、Lanping Ma、Tao Meng、Yuelei Chen、Jingya Li、Jia Li、Jingkang Shen

  DOI：10.1016/j.bmcl.2012.05.123

  日期：2012.7

  The introduction of the multi-objective optimization has dramatically changed the virtual combinatorial library design, which can consider many objectives simultaneously, such as synthesis cost and drug-likeness, thus may increase positive rates of biological active compounds. Here we described a software called CCLab (Combinatorial Chemistry Laboratory) for combinatorial library design based on the multi-objective genetic algorithm. Tests of the convergence ability and the ratio to re-take the building blocks in the reference library were conducted to assess the software in silico, and then it was applied to a real case of designing a 5 x 6 HDAC inhibitor library. Sixteen compounds in the resulted library were synthesized, and the histone deactetylase (HDAC) enzymatic assays proved that 14 compounds showed inhibitory ratios more than 50% against tested 3 HDAC enzymes at concentration of 20 mu g/mL, with IC50 values of 3 compounds comparable to SAHA. These results demonstrated that the CCLab software could enhance the hit rates of the designed library and would be beneficial for medicinal chemists to design focused library in drug development (the software can be downloaded at: http://202.127.30.184:8080/drugdesign.html). (C) 2012 Elsevier Ltd. All rights reserved.