N-[(5-{[2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino}butanoyl)hydrazino]sulfonyl}thien-2-yl)methyl]-2-hydroxybenzamide

• 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
• 英文名称: N-[(5-{[2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino}butanoyl)hydrazino]sulfonyl}thien-2-yl)methyl]-2-hydroxybenzamide
• 英文别名: N-[[5-[[4-[[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino]butanoylamino]sulfamoyl]thiophen-2-yl]methyl]-2-hydroxybenzamide
• 化学式: C₂₂H₂₁ClF₃N₅O₅S₂
• 分子量: 592.019
• InChiKey: XEKJYKJPZRTUGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  186
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2,3-二氯-5-三氟甲基吡啶 在 吡啶 、 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 硫酸 、 一水合肼 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 13.0h， 生成 N-[(5-{[2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]amino}butanoyl)hydrazino]sulfonyl}thien-2-yl)methyl]-2-hydroxybenzamide
  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：ARKINSTALL Stephen

  公开号：US20090005426A1

  公开（公告）日：2009-01-01

  Sulfonyl hydrazide compounds according to formula I geometrical isomers thereof, optically active enantiomers thereof, diastereomers thereof, racemates thereof, and/or pharmaceutically acceptable salts thereof are useful in method for treating a neuronal disorder, an autoimmune disease, a cardiovascular disease, or cancer in a patient in need of such treatment.

  根据I式的磺酰肼化合物及其几何异构体、光学活性对映体、差向异构体、外消旋体和/或药学上可接受的盐，在治疗神经性疾病、自身免疫性疾病、心血管疾病或癌症的方法中，对于需要此类治疗的患者是有用的。
• Therapeutic methods for type I diabetes
  申请人：Davis J. Roger

  公开号：US20060223807A1

  公开（公告）日：2006-10-05

  The invention relates to the treatment and prevention of type I diabetes. More specifically, the invention relates to compounds that treat or prevent the body's immune system from destroying β-cells (i.e., insulin-producing cells in the pancreatic islets of Langerhans) by inhibition of JNK2, selective inhibition of JNK2, or inhibition of the expression of the MAPK9 gene or gene product. In one embodiment, the present invention contemplates the diagnosis, identification, production, and use of compounds which modulate MAPK9 gene expression or the activity of the MAPK9 gene product including but not limited to, JNK2, the nucleic acid encoding MAPK9 and homologues, analogues, and deletions thereof, as well as antisense, ribozyme, triple helix, antibody, and polypeptide molecules as well as small inorganic molecules. The present invention contemplates a variety of pharmaceutical formulations and routes of administration for such compounds.

  本发明涉及 I 型糖尿病的治疗和预防。更具体地说，本发明涉及通过抑制 JNK2、选择性抑制 JNK2 或抑制 MAPK9 基因或基因产物的表达来治疗或防止机体免疫系统破坏 β 细胞（即胰岛中的胰岛素分泌细胞）的化合物。在一个实施方案中，本发明考虑诊断、鉴定、生产和使用调节 MAPK9 基因表达或 MAPK9 基因产物活性的化合物，包括但不限于 JNK2、编码 MAPK9 的核酸及其同源物、类似物和缺失物，以及反义、核糖酶、三重螺旋、抗体和多肽分子以及无机小分子。本发明考虑了此类化合物的各种药物制剂和给药途径。
• Therapeutic Methods For Type I Diabetes
  申请人：Davis Roger J.

  公开号：US20120208846A1

  公开（公告）日：2012-08-16

  The invention relates to the treatment and prevention of type I diabetes. More specifically, the invention relates to compounds that treat or prevent the body's immune system from destroying β-cells (i.e., insulin-producing cells in the pancreatic islets of Langerhans) by inhibition of JNK2, selective inhibition of JNK2, or inhibition of the expression of the MAPK9 gene or gene product. In one embodiment, the present invention contemplates the diagnosis, identification, production, and use of compounds which modulate MAPK9 gene expression or the activity of the MAPK9 gene product including but not limited to, JNK2, the nucleic acid encoding MAPK9 and homologues, analogues, and deletions thereof, as well as antisense, ribozyme, triple helix, antibody, and polypeptide molecules as well as small inorganic molecules. The present invention contemplates a variety of pharmaceutical formulations and routes of administration for such compounds.
• Therapeutic Methods for Type I Diabetes
  申请人：UNIVERSITY OF MASSACHUSETTS

  公开号：US20150313881A1

  公开（公告）日：2015-11-05

  The invention relates to the treatment and prevention of type I diabetes. More specifically, the invention relates to compounds that treat or prevent the body's immune system from destroying β-cells (i.e., insulin-producing cells in the pancreatic islets of Langerhans) by inhibition of JNK2, selective inhibition of JNK2, or inhibition of the expression of the MAPK9 gene or gene product. In one embodiment, the present invention contemplates the diagnosis, identification, production, and use of compounds which modulate MAPK9 gene expression or the activity of the MAPK9 gene product including but not limited to, JNK2, the nucleic acid encoding MAPK9 and homologues, analogues, and deletions thereof, as well as antisense, ribozyme, triple helix, antibody, and polypeptide molecules as well as small inorganic molecules. The present invention contemplates a variety of pharmaceutical formulations and routes of administration for such compounds.
• US7432286B1
  申请人：——

  公开号：US7432286B1

  公开（公告）日：2008-10-07