Ethyl 3-(4-chlorophenyl)-4-cyano-5-propan-2-ylsulfanylthiophene-2-carboxylate | 882278-95-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: Ethyl 3-(4-chlorophenyl)-4-cyano-5-propan-2-ylsulfanylthiophene-2-carboxylate
• CAS: 882278-95-7
• 化学式: C₁₇H₁₆ClNO₂S₂
• 分子量: 365.905
• InChiKey: HBIZYEFSDLQLDA-UHFFFAOYSA-N

物化性质

• 沸点：
  507.5±50.0 °C(predicted)
• 密度：
  1.32±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl 3-(4-chlorophenyl)-4-cyano-5-propan-2-ylsulfanylthiophene-2-carboxylate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以93%的产率得到3-(4-Chlorophenyl)-4-cyano-5-(isopropylthio)thiophene-2-carboxylic acid
  参考文献：
  名称：

  在芳基噻吩系列中发现一类新型的蛋白质法呢基转移酶抑制剂

  摘要：

  ICSN化学文库的筛选导致发现3-（4-氯苯基）-4-氰基-5-硫代烷基噻吩2-羧酸作为有效的法呢基转移酶抑制剂。酶动力学研究表明，该原始FTI系列属于CaaX竞争性抑制剂类别。SAR的初步研究使我们能够将IC 50从110 nM提高到7.5 nM。

  DOI：

  10.1021/jm901280q
• 作为产物：
  描述：

  2-(bis(isopropylthio)methylene)malononitrile 在 四(三苯基膦)钯 、 亚硝酸特丁酯 、 potassium carbonate 、 copper(ll) bromide 作用下， 以 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 7.17h， 生成 Ethyl 3-(4-chlorophenyl)-4-cyano-5-propan-2-ylsulfanylthiophene-2-carboxylate
  参考文献：
  名称：

  New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

  摘要：

  A new synthetic pathway was devised to reach tetrasubstituted 3-arylthiophene 2-carboxylic acids in a three-step solid-phase synthesis. This very efficient methodology provided more than 20 new compounds that were evaluated for their ability to inhibit protein farnesyltransferase from different species as well as Trypanosoma brucei and Plasmodium falciparum proliferation.

  DOI：

  10.3109/14756366.2011.643302

文献信息

• SNAr and Palladium-Catalyzed Reactions of Deactivated Thiophene: Application to the Synthesis of Protein Farnesyltransferase Inhibitors
  作者：Sébastien Lethu、Joëlle Dubois

  DOI：10.1002/ejoc.201100215

  日期：2011.7

  5-thioether moiety of our previously identified hit thiophene compound upon protein farnesyltransferase inhibition, we synthesized a new library of 3-(4-chlorophenyl)-4-cyanothiophene-2-carboxylic derivatives through the application of aromatic nucleophilic substitutions benefiting from a sulfone-based leaving group and by direct palladium-catalyzed reactions on a thioalkylthiophene. This small library of

  为了研究我们先前鉴定的命中噻吩化合物的 5-硫醚部分对蛋白质法呢基转移酶抑制的影响，我们通过应用芳香亲核试剂合成了一个新的 3-(4-氯苯基)-4-氰基噻吩-2-羧酸衍生物文库。取代受益于基于砜的离去基团和直接钯催化的硫代烷基噻吩反应。然后评估该酯衍生物及其相应酸的小型文库的蛋白质法呢基转移酶抑制活性；一些图书馆成员表现出有希望的亚微摩尔活性。
• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT NEUROINFLAMMATORY DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160303146A1

  公开（公告）日：2016-10-20

  This invention provides methods and pharmaceutical compositions that can treat neuroinflammatory disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT AUTOIMMUNE DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160375041A1

  公开（公告）日：2016-12-29

  The invention provides methods and pharmaceutical compositions that can treat autoimmune disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• [EN] INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT AUTOIMMUNE DISORDERS<br/>[FR] INHIBITION DE VOIES DE BIOSYNTHÈSE D'ISOPRÉNOÏDES POUR TRAITER DES TROUBLES AUTO-IMMUNS
  申请人：TABACZYNSKI DAVID A

  公开号：WO2015084721A1

  公开（公告）日：2015-06-11

  The invention provides methods and pharmaceutical compositions that can treat autoimmune disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• Discovery of a New Class of Protein Farnesyltransferase Inhibitors in the Arylthiophene Series
  作者：Sébastien Lethu、Maryon Ginisty、Damien Bosc、Joëlle Dubois

  DOI：10.1021/jm901280q

  日期：2009.10.22

  Screening of the ICSN chemical library led to the discovery of 3-(4-chlorophenyl)-4-cyano-5-thioalkylthiophene 2-carboxylic acids as potent farnesyltransferase inhibitors. Enzymatic kinetic studies showed that this original FTI series belongs to the CaaX competitive inhibitor class. Preliminary SAR studies allowed us to improve the IC50 from 110 to 7.5 nM.

  ICSN化学文库的筛选导致发现3-（4-氯苯基）-4-氰基-5-硫代烷基噻吩2-羧酸作为有效的法呢基转移酶抑制剂。酶动力学研究表明，该原始FTI系列属于CaaX竞争性抑制剂类别。SAR的初步研究使我们能够将IC 50从110 nM提高到7.5 nM。