2,5-dimethoxythiobenzoic acid N-methylhydrazide | 488833-27-8

• 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: 2,5-dimethoxythiobenzoic acid N-methylhydrazide
• 英文别名: 2,5-dimethoxy-N-methylbenzenecarbothiohydrazide
• CAS: 488833-27-8
• 化学式: C₁₀H₁₄N₂O₂S
• 分子量: 226.299
• InChiKey: MZXGXCMYRIAHGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  79.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  丙二酸 、 2,5-dimethoxythiobenzoic acid N-methylhydrazide 在 1-丙基磷酸酐 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到N′¹,N′³-bis[(2,5-dimethoxyphenyl)carbonothioyl]-N′¹,N′³-dimethylmalonohydrazide
  参考文献：
  名称：

  N，1，N'3-二烷基-N'1，N'3-双（芳基碳硫基）丙二酰肼通过丙基膦酸酐偶联物的简便合成

  摘要：

  专用于成业袁教授和有机化学研究所上海（CAS）的李昕戴教授在他们的90个之际个生日 抽象 一种抗癌剂伊利司莫及其类似物，容易且方便的合成方法Ñ ' 1，Ñ ' 3 -二烷基Ñ ' 1，Ñ ' 3双（arylcarbonothioyl）malonohydrazides，通过直接耦合Ñ -烷基- ñ - （取代的）benzothiohydrazides和使用丙基膦酸酐（T3P取代的丙二酸®）已经开发下非常温和的条件。 一种抗癌剂伊利司莫及其类似物，容易且方便的合成方法Ñ ' 1，Ñ ' 3 -二烷基Ñ ' 1，Ñ ' 3双（arylcarbonothioyl）malonohydrazides，通过直接耦合Ñ -烷基- ñ - （取代的）benzothiohydrazides和使用丙基膦酸酐（T3P取代的丙二酸®）已经开发下非常温和的条件。

  DOI：

  10.1055/s-0034-1378664
• 作为产物：
  描述：

  2,5-dimethoxy-N-methylbenzohydrazide 在 P₂S₂ 作用下， 以 氘代苯 为溶剂， 生成 2,5-dimethoxythiobenzoic acid N-methylhydrazide
  参考文献：
  名称：

  Syntheses and antitumor activities of N′1,N′3-dialkyl-N′1,N′3-di-(alkylcarbonothioyl) malonohydrazide: The discovery of elesclomol

  摘要：

  A series of N'(1),N'(3)-dialkyl-N'(1),N'(3)-di(alkylcarbonothioyl) malonohydrazides have been designed and synthesized as anticancer agents by targeting oxidative stress and Hsp70 induction. Structure-activity relationship (SAR) studies lead to the discovery of STA-4783 (elesclomol), a novel small molecule that has been evaluated in a number of clinical trials as an anticancer agent in combination with Taxol. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.032

文献信息

• Taxol enhancer compounds
  申请人：Synta Pharmaceuticals Corp.

  公开号：US20030195258A1

  公开（公告）日：2003-10-16

  Disclosed is a compound represented by the Structural Formula (I): 1 Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C═Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R 7 R 8 )—. R 1 and R 2 are independently an aryl group or a substituted aryl group, R 3 and R 4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 5 -R 6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 7 and R 8 are each independently —H, an aliphatic or substituted aliphatic group, or R 7 is —H and R 8 is a substituted or unsubstituted aryl group, or, R 7 and R 8 , taken together, are a C1-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with taxol or an analog of taxol.

  揭示的是一种由结构式（I）表示的化合物： Y是一个共价键，一个苯基团或一个取代或未取代的直链烃基团。此外，Y与其结合的两个>C═Z基团一起，是一个取代或未取代的芳香基团。优选地，Y是一个共价键或—C(R7R8)—。R1和R2分别是芳基或取代芳基，R3和R4分别是—H，一个脂肪基，一个取代的脂肪基，一个芳基或一个取代的芳基。R5-R6分别是—H，一个脂肪基，一个取代的脂肪基，一个芳基或一个取代的芳基。R7和R8各自独立地是—H，一个脂肪或取代的脂肪基，或者R7是—H，R8是一个取代或未取代的芳基，或者R7和R8一起是一个C1-C6取代或未取代的烷基基团。Z是═O或═S。还公开了包含本发明化合物的药物组合物以及药学上可接受的载体或稀释剂。还公开了一种通过向患有癌症的受试者投与结构式（I）的化合物联合紫杉醇或紫杉醇类似物来治疗患者的方法。
• Synthesis of taxol enhancers
  申请人：Shionogi BioResearch Corp.

  公开号：US20030069225A1

  公开（公告）日：2003-04-10

  Disclosed is a method of preparing a thiohydrazide product compound from a hydrazide starting compound. The hydrazide starting compound is represented by Structural Formula (I): 1 The thiohydrazide product compound is represented by Structural Formula (II): 2 In Structural Formulas (I)-(II), R 1 and R 2 are independently an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R 1 and R 2 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. When R 2 is an aryl group or a substituted aryl group, then R 5 is a hydrazine protecting group; and when R 2 is an aliphatic or substituted aliphatic group, then R 5 is —H or a hydrazine protecting group. R 10 is —H or a substituted or unsubstituted alkyl group. The method comprising the step of reacting the starting compound with a thionylating reagent.

  本发明涉及一种从一个酰肼起始化合物制备硫代酰肼产物化合物的方法。所述酰肼起始化合物由结构式（I）表示：1 所述硫代酰肼产物化合物由结构式（II）表示：2 在结构式（I）-（II）中，R1和R2分别独立地是脂肪基，取代的脂肪基，芳基或取代的芳基，或者R1和R2连同它们连接的碳和氮原子形成一个非芳杂环环，该杂环可以与一个芳环融合。当R2是芳基或取代的芳基时，R5是一个肼保护基；当R2是脂肪基或取代的脂肪基时，R5是-H或肼保护基。R10是-H或取代或未取代的烷基。所述方法包括将起始化合物与硫酰化试剂反应的步骤。
• Treatment for cancers
  申请人：Synta Pharmaceuticals Corporation

  公开号：US20040225016A1

  公开（公告）日：2004-11-11

  One embodiment of the present invention is a method of treating a subject with a multi-drug resistant cancer. The method comprises administering to the subject an effective amount of a compound represented by Structural Formula (I): 1 Y is a covalent bond or a substituted or unsubstituted straight chained hydrocarbyl group, or, Y, taken together with both>C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. R 1 -R 4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group, or R 1 and R 3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R 2 and R 4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. Preferably R 1 and R 2 are the same and R 3 and R 4 are the same. R 5 -R 6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. Z is ═O or ═S.

  本发明的一种实施例是一种治疗多药耐药癌症患者的方法。该方法包括向患者施用式(I)所表示的化合物的有效量：其中1Y是共价键或取代或未取代的直链烃基，或Y与其结合的两个>C=Z基团一起形成取代或未取代的芳香族基团。R1-R4独立地为—H、脂肪基、取代脂肪基、芳基或取代芳基，或者R1和R3与它们结合的碳和氮原子以及/或R2和R4与它们结合的碳和氮原子形成一个非芳杂环环，可选地与芳环融合。最好的是R1和R2相同，R3和R4相同。R5-R6独立地为—H、脂肪基、取代脂肪基、芳基或取代芳基。Z为═O或═S。
• Paclitaxel enhancer compounds
  申请人：Koya Keizo

  公开号：US20080214655A1

  公开（公告）日：2008-09-04

  Disclosed is a compound represented by the Structural Formula (I): Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R 7 R 8 )—. R 1 and R 2 are independently an aryl group or a substituted aryl group, R 3 and R 4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 5 -R 6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 7 and R 8 are each independently —H, an aliphatic or substituted aliphatic group, or R 7 is —H and R 8 is a substituted or unsubstituted aryl group, or, R 7 and R 8 , taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with Paclitaxel or an analog of Paclitaxel.

  本发明揭示了一种由结构式（I）表示的化合物： 其中，Y是共价键，苯基或取代或未取代的直链烃基团。此外，Y与其连接的两个>C=Z基团一起，是取代或未取代的芳香族基团。优选地，Y是共价键或—C（R7R8）—。R1和R2分别是芳基基团或取代芳基基团，R3和R4分别是—H、脂肪基、取代脂肪基、芳基或取代芳基。R5-R6分别是—H、脂肪基、取代脂肪基、芳基或取代芳基。R7和R8各自独立地是—H、脂肪基或取代脂肪基，或者R7是—H，R8是取代或未取代的芳基基团，或者R7和R8一起是C2-C6取代或未取代的烷基基团。Z是═O或═S。本发明还揭示了包含本发明化合物和药学可接受的载体或稀释剂的制药组合物。本发明还揭示了一种通过将Paclitaxel或Paclitaxel类似物与结构式（I）的化合物联合给予受试者治疗癌症的方法。
• PACLITAXEL ENHANCER COMPOUNDS
  申请人：Koya Keizo

  公开号：US20100280075A1

  公开（公告）日：2010-11-04

  Disclosed is a compound represented by the Structural Formula (I): Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C═Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R 7 R 8 )—. R 1 and R 2 are independently an aryl group or a substituted aryl group, R 3 and R 4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 5 -R 6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R 7 and R g are each independently —H, an aliphatic or substituted aliphatic group, or R 7 is —H and R g is a substituted or unsubstituted aryl group, or, R 7 and R 8 , taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with Paclitaxel or an analog of Paclitaxel.

  本发明公开了一种化合物，其结构式表示为（I）：其中，Y是共价键，苯基或取代或未取代的直链烃基。此外，将Y与其结合的两个>C═Z基团结合起来，形成取代或未取代的芳香族基团。优选地，Y是共价键或—C（R7R8）—。R1和R2分别是芳基或取代芳基，R3和R4分别是—H，脂肪基，取代脂肪基，芳基或取代芳基。R5-R6分别是—H，脂肪基，取代脂肪基，芳基或取代芳基。R7和Rg各自独立地是—H，脂肪基或取代脂肪基，或者R7是—H，而Rg是取代或未取代的芳基。或者，R7和R8一起是C2-C6取代或未取代的烷基基团。Z是═O或═S。本发明还公开了包含本发明化合物和药学上可接受的载体或稀释剂的药物组合物。本发明还公开了一种通过向患有癌症的受试者同时给予结构式（I）化合物和紫杉醇或紫杉醇类似物来治疗患者的方法。