4-(3-氯-5-三氟甲基吡啶-2-基氨基)丁酸酰肼 | 332361-09-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 4-(3-氯-5-三氟甲基吡啶-2-基氨基)丁酸酰肼
• 英文名称: 4-(3-chloro-5-trifluoromethylpyridin-2-ylamino)butyric acid hydrazide
• 英文别名: 4-(3-Chloro-5-trifluoromethyl-pyridin-2-ylamino)-butyric acid hydrazide；4-{[3-Chloro-5-(trifluoromethyl)-2-pyridinyl]amino}butanohydrazide；4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanehydrazide
• CAS: 332361-09-8
• 化学式: C₁₀H₁₂ClF₃N₄O
• 分子量: 296.68
• InChiKey: MDBNRJJDWCZXAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  80
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(3-氯-5-三氟甲基吡啶-2-基氨基)丁酸酰肼 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：

  2,3-二氯-5-三氟甲基吡啶 在 硫酸 、 一水合肼 作用下， 以 甲醇 为溶剂， 反应 6.5h， 生成 4-(3-氯-5-三氟甲基吡啶-2-基氨基)丁酸酰肼
  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。
• Design, Synthesis, and Biological Activity of Novel, Potent, and Selective (Benzoylaminomethyl)thiophene Sulfonamide Inhibitors of c-Jun-N-Terminal Kinase
  作者：Thomas Rückle、Marco Biamonte、Tania Grippi-Vallotton、Steve Arkinstall、Yves Cambet、Montserrat Camps、Christian Chabert、Dennis J. Church、Serge Halazy、Xuliang Jiang、Isabelle Martinou、Anthony Nichols、Wolfgang Sauer、Jean-Pierre Gotteland

  DOI：10.1021/jm031112e

  日期：2004.12.1

  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.