4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carbothioamide | 913264-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carbothioamide
• 英文别名: 4-(1,2-benzisothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carbothioamide；4-(1,2-benzothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carbothioamide
• CAS: 913264-45-6
• 化学式: C₁₈H₁₇ClN₄S₂
• 分子量: 388.945
• InChiKey: MDRFEKSMEAOGOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  91.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氯-1,2-苯并异噻唑 以 乙醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carbothioamide
  参考文献：
  名称：

  An efficient synthesis and biological screening of benzofuran and benzo[ d ]isothiazole derivatives for Mycobacterium tuberculosis DNA GyrB inhibition

  摘要：

  A series of twenty eight molecules of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate and 3-(piperazin-1-yl)benzo[d]isothiazole were designed by molecular hybridization of thiazole aminopiperidine core and carbamide side chain in eight steps and were screened for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antitubercular activity, cytotoxicity and protein-inhibitor interaction assay through differential scanning fluorimetry. Also the orientation and the ligand-protein interactions of the top hit molecules with MS DNA gyrase B subunit active site were investigated applying extra precision mode (XP) of Glide. Among the compounds studied, 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide (26) was found to be the most promising inhibitor with an MS GyrB IC50 of 1.77 +/- 0.23 mu M, 0.42 +/- 0.23 against MTB DNA gyrase, MTB MIC of 3.64 mu M, and was not cytotoxic in eukaryotic cells at 100 mu M. Moreover the interaction of protein-ligand complex was stable and showed a positive shift of 3.5 degrees C in differential scanning fluorimetric evaluations. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.016

文献信息

• Compounds Useful In Therapy
  申请人：Bryans Justin Stephen

  公开号：US20080188478A1

  公开（公告）日：2008-08-07

  Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: R 1 represents a group selected from H, CF 3 , and C 1-6 alkyl (optionally substituted by C 1-6 alkyloxy or triazolyl); R 2 represents halo; Ring A represents a 5- or 6-membered heterocyclic ring containing at least one N atom (the ring being optionally bridged with two or more carbon atoms); R 3 represents a 5- or 6-membered heterocyclic ring containing at least one atom selected from N, O or S, the heterocyclic ring being optionally substituted by one or more groups selected from C 1-6 alkyl oxo or NH 2 , the heterocyclic ring being further optionally fused to a 5- or 6-membered aryl or heterocyclic ring containing at least one atom selected from N, O or S, the fused aryl or heterocyclic ring being substituted by one or more halo atoms; are useful for treating a disorder for which a V1a antagonist is indicated, in particular, dysmenorrhea.

  式(I)的化合物或其药学上可接受的衍生物，其中： R1表示从H，CF3和C1-6烷基（可选地被C1-6烷氧基或三唑基取代）中选择的基团； R2表示卤素； 环A表示含有至少一个N原子的5-或6成员杂环，（该环可与两个或更多个碳原子桥接）； R3表示含有至少一个从N，O或S中选择的原子的5-或6成员杂环，该杂环可被选自C1-6烷基氧或NH2的一个或多个基团取代，该杂环进一步可融合到一个含有至少一个从N，O或S中选择的原子的5-或6成员芳香族或杂环中，该融合的芳香族或杂环被一个或多个卤素原子取代； 用于治疗需要V1a拮抗剂的疾病，特别是痛经。
• An efficient synthesis and biological screening of benzofuran and benzo[ d ]isothiazole derivatives for Mycobacterium tuberculosis DNA GyrB inhibition
  作者：Kummetha Indrasena Reddy、Konduri Srihari、Janupally Renuka、Komanduri Shruthi Sree、Aruna Chuppala、Variam Ullas Jeankumar、Jonnalagadda Padma Sridevi、Kondra Sudhakar Babu、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.bmc.2014.10.016

  日期：2014.12

  A series of twenty eight molecules of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate and 3-(piperazin-1-yl)benzo[d]isothiazole were designed by molecular hybridization of thiazole aminopiperidine core and carbamide side chain in eight steps and were screened for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antitubercular activity, cytotoxicity and protein-inhibitor interaction assay through differential scanning fluorimetry. Also the orientation and the ligand-protein interactions of the top hit molecules with MS DNA gyrase B subunit active site were investigated applying extra precision mode (XP) of Glide. Among the compounds studied, 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide (26) was found to be the most promising inhibitor with an MS GyrB IC50 of 1.77 +/- 0.23 mu M, 0.42 +/- 0.23 against MTB DNA gyrase, MTB MIC of 3.64 mu M, and was not cytotoxic in eukaryotic cells at 100 mu M. Moreover the interaction of protein-ligand complex was stable and showed a positive shift of 3.5 degrees C in differential scanning fluorimetric evaluations. (C) 2014 Elsevier Ltd. All rights reserved.