5-Diallylaminomethyl-thiophene-2-sulfonyl chloride | 332082-90-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-Diallylaminomethyl-thiophene-2-sulfonyl chloride
• 英文别名: 5-N,N-diallylaminomethylthiophene-2-sulfonyl chloride；5-diallylaminomethylthiophene-2-sulfonyl chloride；5-[[bis(prop-2-enyl)amino]methyl]thiophene-2-sulfonyl chloride
• CAS: 332082-90-3
• 化学式: C₁₁H₁₄ClNO₂S₂
• 分子量: 291.823
• InChiKey: RTSXKBQXXIFLKN-UHFFFAOYSA-N

物化性质

• 沸点：
  367.5±42.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  74
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-Diallylaminomethyl-thiophene-2-sulfonyl chloride 在 吡啶 、 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 6.0h， 生成 N'-[5-(aminomethyl)thiophen-2-yl]sulfonyl-4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanehydrazide
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel, Potent, and Selective (Benzoylaminomethyl)thiophene Sulfonamide Inhibitors of c-Jun-N-Terminal Kinase

  摘要：

  Several lines of evidence support the hypothesis that c-Jun N-terminal kinases (JNKs) play a critical role in a wide range of disease states including cell death (apoptosis)-related and inflammatory disorders (epilepsy, brain, heart and renal ischemia, neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel syndrome). The screening of a compound collection led to the identification of a 2-(benzoylaminomethyl)thiophene sulfonamide (AS004509, compound I) as a potent and selective JNK inhibitor. Chemistry and structure-activity relationship (SAR) studies performed around this novel kinase-inhibiting motif indicated that the left and central parts of the molecule were instrumental to maintaining potency at the enzyme. Accordingly, we investigated the JNK-inhibiting properties of a number of variants of the right-hand moiety of the molecule, which led to the identification of 2-(benzoylaminomethyl)thiophene sulfonamide benzotriazole (AS600292, compound 50a), the first potent and selective JNK inhibitor of this class which demonstrates a protective action against neuronal cell death induced by growth factor and serum deprivation.

  DOI：

  10.1021/jm031112e
• 作为产物：
  描述：

  2-噻吩甲胺 在 叔丁基锂 、 N,N-二异丙基乙胺 作用下， 以 乙醚 、 二氯甲烷 、 正戊烷 为溶剂， 反应 0.92h， 生成 5-Diallylaminomethyl-thiophene-2-sulfonyl chloride
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity of Novel, Potent, and Selective (Benzoylaminomethyl)thiophene Sulfonamide Inhibitors of c-Jun-N-Terminal Kinase

  摘要：

  Several lines of evidence support the hypothesis that c-Jun N-terminal kinases (JNKs) play a critical role in a wide range of disease states including cell death (apoptosis)-related and inflammatory disorders (epilepsy, brain, heart and renal ischemia, neurodegenerative diseases, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel syndrome). The screening of a compound collection led to the identification of a 2-(benzoylaminomethyl)thiophene sulfonamide (AS004509, compound I) as a potent and selective JNK inhibitor. Chemistry and structure-activity relationship (SAR) studies performed around this novel kinase-inhibiting motif indicated that the left and central parts of the molecule were instrumental to maintaining potency at the enzyme. Accordingly, we investigated the JNK-inhibiting properties of a number of variants of the right-hand moiety of the molecule, which led to the identification of 2-(benzoylaminomethyl)thiophene sulfonamide benzotriazole (AS600292, compound 50a), the first potent and selective JNK inhibitor of this class which demonstrates a protective action against neuronal cell death induced by growth factor and serum deprivation.

  DOI：

  10.1021/jm031112e

文献信息

• Pharmaceutically active sulfonyl hydrazide derivatives
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1088822A1

  公开（公告）日：2001-04-04

  The present invention is related to sulfonyl hydrazide derivatives according to formula I with its geometrical isomers, in an optically active form as enantiomers, diastereomers, as well as in the form of racemates, as well as pharmaceutically acceptable salts thereof, wherein Ar1 and Ar2 are independently from each other an unsubstituted or substituted aryl or heteroaryl group, X1 and X2 are independently from each other O or S; R1, R2, R3 are independently from each other hydrogen or a C1-C6-alkyl substituent or R1 forms a substituted or unsubstituted 5-6-membered saturated or unsaturated ring with Ar1; or R2 and R3 form a substituted or unsubstituted 5-6-membered saturated or unsaturated ring; n is an integer from 0 to 5; G is selected from a group comprising or consisting of an unsubstituted or substituted 4-8-membered heterocycle containing at least one heteroatom, or G is a substituted or unsubstituted C1-C6-alkyl group; for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such sulfonyl hydrazide derivatives. Said sulfonyl hydrazide derivatives are efficient modulators of the JNK pathway, they are in particular efficient inhibitors of JNK 2 and 3. The present invention is furthermore related to novel sulfonyl hydrazide derivatives as well as to methods of their preparation.

  本发明涉及按照式I的磺酰基腙衍生物及其几何异构体，以对映体、二对映体的光学活性形式，以及它们的盐的药学上可接受的形式，其中Ar1和Ar2分别独立地是未取代或取代的芳基或杂环芳基，X1和X2分别独立地是O或S；R1、R2、R3分别独立地是氢或C1-C6-烷基取代基，或R1与Ar1形成取代或未取代的5-6元饱和或不饱和环；或R2和R3形成取代或未取代的5-6元饱和或不饱和环；n是0到5的整数；G选自包含或仅包含至少一个杂原子的未取代或取代的4-8元杂环的群，或G是取代或未取代的C1-C6烷基基团；用作药学活性化合物，以及含有这种磺酰基腙衍生物的制药配方。所述磺酰基腙衍生物是JNK途径的高效调节剂，特别是JNK 2和3的高效抑制剂。本发明还涉及新型磺酰基腙衍生物以及其制备方法。
• Pharmaceutically active hydrophilic sulfonamide derivatives as inhibitors of protein JunKinases
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1193267A1

  公开（公告）日：2002-04-03

  The present invention is related to substantially hydrophilic sulfonamide derivatives, or sulfonamide derivatives having a substantially hydrophilic moiety, of formula I notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such sulfonamide derivatives. Said sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK 2 and 3. The present invention is furthermore related to novel sulfonamide derivatives as well as to methods of their preparation. The compounds of formula I according to the present invention being suitable pharmaceutical agents are those wherein Ar1 is a substituted or unsubstituted aryl or heteroaryl; Ar2 is an aryl or heteroaryl group carrying at least one hydrophilic substituent; X is O or S, preferably O; R1 is hydrogen or a C1-C6-alkyl group, or R1 forms a substituted or unsubstituted 5-6-membered saturated or unsaturated ring with Ar1; n is an integer from 0 to 5, preferably between 1-3 and most preferred 1; Y within formula I is an unsubstituted or a substituted 4-12-membered saturated cyclic or bicyclic alkyl containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula I thus providing a sulfonamide.

  本发明涉及具有基本亲水性磺胺基衍生物或具有基本亲水性基团的磺胺基衍生物，其化学式为I，特别用作药用活性化合物，以及含有这种磺胺基衍生物的药物配方。所述磺胺基衍生物是JNK途径的高效调节剂，特别是JNK 2和3的高效选择性抑制剂。本发明还涉及新型磺胺基衍生物以及其制备方法。 根据本发明的化学式I的化合物适用于药用剂的那些是： Ar1是取代或未取代的芳基或杂芳基； Ar2是携带至少一个亲水取代基的芳基或杂芳基； X是O或S，优选O； R1是氢或C1-C6烷基，或R1与Ar1形成取代或未取代的5-6元饱和或不饱和环； n是0到5之间的整数，优选在1-3之间，最优选1； 化学式I中的Y是未取代或取代的含有至少一个氮原子的4-12元饱和环或双环烷基，其中所述环中的一个氮原子与化学式I的磺酰基形成键合，从而提供磺胺基。
• Pharmaceutically active sulfonamide derivatives bearing both lipophilic and ionisable moieties as inhibitors of protein Junkinases
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1193268A1

  公开（公告）日：2002-04-03

  The present invention is related to sulfonamide derivatives having a lipophilic moiety and which are substantially soluble under physiological conditions. Said compounds are notably for use as pharmaceutically active compounds. The present invention also related to pharmaceutical formulations containing such sulfonamide derivatives. Said sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK 2 and 3. The present invention is furthermore related to novel sulfonamide derivatives as well as to methods of their preparation. The compounds of formula I according to the present invention being suitable pharmaceutical agents are those wherein Ar1 and Ar2 are independently from each other substituted or unsubstituted aryl or heteroaryl groups, X is O or S, preferably O; R1 is hydrogen or a C1-C6-alkyl group, or R1 forms a substituted or unsubstituted 5-6-membered saturated or unsaturated ring with Ar1; n is an integer from 0 to 5, preferably between 1-3 and most preferred 1; Y within formula I is an unsubstituted or a substituted 4-12-membered saturated cyclic or bicyclic alkyl which is substituted with at least one ionisable moiety to which a lipophilic chain is attached and which is containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula I thus providing a sulfonamide.ring is forming a bond with the sulfonyl group of formula I thus providing a sulfonamide.

  本发明涉及具有亲脂基团并在生理条件下基本可溶的磺胺基衍生物。所述化合物特别适用作药用活性化合物。本发明还涉及含有这种磺胺基衍生物的药物配方。所述磺胺基衍生物是JNK途径的高效调节剂，特别是JNK 2和3的高效和选择性抑制剂。本发明还涉及新型磺胺基衍生物以及它们的制备方法。 根据本发明的式I化合物适用于药用剂的那些化合物是这样的： Ar1和Ar2分别独立地是取代或未取代的芳基或杂环芳基， X是O或S，优选为O； R1是氢或C1-C6烷基，或R1与Ar1形成取代或未取代的5-6元饱和或不饱和环； n是0到5的整数，优选为1-3之间，最优选为1； 式I中的Y是未取代或取代的4-12元饱和环或双环烷基，其上取代有至少一个可离子化基团，该基团连接有一个亲脂链，并且含有至少一个氮原子，其中所述环中的一个氮原子与式I的磺酰基形成键合，从而提供磺胺基。
• Pharmaceutically active sulfonyl amino acid derivatives
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1088815A1

  公开（公告）日：2001-04-04

  The present invention is related to sulfonyl amino acid derivatives notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such sulfonyl amino acid derivatives. Said sulfonyl amino acid are efficient modulators of the JNK pathway, they are in particular efficient inhibitors of JNK 2 and 33. The present invention is furthermore related to novel sulfonyl amino acid derivatives as well as to methods of their preparation.

  本发明涉及磺酰氨基酸衍生物，特别是用作药物活性化合物，以及含有此类磺酰氨基酸衍生物的制药配方。所述磺酰氨基酸是JNK途径的有效调节剂，它们特别是JNK 2和33的有效抑制剂。本发明还涉及新型磺酰氨基酸衍生物及其制备方法。
• Pharmaceutically active sulfonamide derivatives
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1088821A1

  公开（公告）日：2001-04-04

  The present invention is related to sulfonamide derivatives of formula I notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such sulfonamide derivatives. Said sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK 2 and 3. The present invention is furthermore related to novel sulfonamide derivatives as well as to methods of their preparation. The compounds of formula I according to the present invention being suitable pharmaceutical agents are those wherein Ar1 and Ar2 are independently from each other substituted or unsubstituted aryl or heteroaryl groups, X is O or S, preferably O; R1 is hydrogen or a C1-C6-alkyl group, preferably H, or R1 forms a substituted or unsubstituted 5-6-membered saturated or non-saturated ring with Ar1; n is an integer from 0 to 5, preferably between 1-3 and most preferred 1. Y within formula I is an unsubstituted or a substituted 4-12-membered saturated cyclic or bicyclic alkyl containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula I thus providing the sulfonamide.

  本发明涉及公式I的磺酰胺衍生物，特别是用作药物活性化合物，以及含有这种磺酰胺衍生物的制药配方。所述磺酰胺衍生物是JNK途径的高效调节剂，特别是JNK2和3的高效且选择性抑制剂。本发明还涉及新型磺酰胺衍生物以及它们的制备方法。本发明中适合用作药物剂的公式I化合物是Ar1和Ar2分别独立于彼此的取代或未取代芳基或杂环芳基基团，X为O或S，优选为O；R1为氢或C1-C6烷基，优选为H，或R1与Ar1形成取代或未取代的5-6成员饱和或不饱和环；n为0到5的整数，优选为1-3，最优选为1。公式I中的Y是未取代或取代的4-12成员饱和环或双环烷基，其中至少有一个氮原子，该环中的一个氮原子与公式I中的磺酰基形成键合，从而提供磺酰胺。