N-(4-chlorophenyl)-N-{2-oxo-2-[(2Z)-2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)hydrazino]ethyl}-2-thiophenesulfonamide

• 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: N-(4-chlorophenyl)-N-{2-oxo-2-[(2Z)-2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)hydrazino]ethyl}-2-thiophenesulfonamide
• 英文别名: N-(4-chlorophenyl)-N-[2-oxo-2-[2-(2-oxoindol-3-yl)hydrazinyl]ethyl]thiophene-2-sulfonamide
• 化学式: C₂₀H₁₅ClN₄O₄S₂
• 分子量: 474.948
• InChiKey: QCIUZJCYSFMRCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  107.94
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  2-Thienylsulfonyl-p-chloranilid 在 sodium hydride 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-chlorophenyl)-N-{2-oxo-2-[(2Z)-2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)hydrazino]ethyl}-2-thiophenesulfonamide
  参考文献：
  名称：

  发现和开发新型的有效，选择性，口服活性催产素受体拮抗剂。

  摘要：

  我们报告了一种新型的强力催产素受体拮抗剂的化学类别，它显示了对紧密相关的加压素受体（V1a，V1b，V2）的高度选择性。当通过静脉内而非口服途径给药时，最初的化合物7在早产的动物模型中显示出活性。围绕不同结构元件进行的逐步SAR研究表明，一个位置即芳烃磺酰基部分易于改变结构。因此，该位置用于引入各种取代基以改善物理化学性质。发现一些所得的类似物在体外效力和水溶性方面均优于7，这转化为在静脉内和口服施用后在动物模型中的功效显着改善。最好的化合物73

  DOI：

  10.1021/jm050645f

文献信息

• Pharmaceutically active sulfanilide derivatives
  申请人：——

  公开号：US20040072816A1

  公开（公告）日：2004-04-15

  The present invention relates to sulfanilide derivatives of formula (I), in which R 1 and R 2 are optionally substituted aryl and heteroaryl groups and the other variables are as defined in the claims, for use as pharmaceutically active compounds, as well as pharmaceutical formulations containing such sulfanilide derivatives. Said derivatives are useful in the treatment and/or prevention of preterm labor, premature birth, dysmenorrhea, inappropriate secretion of vasopressin, congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome and ocular hypertension. In particular, the present invention is related to sulfanilide derivatives displaying a substantial modulatory, in particular antagonistic activity, of the oxytocin and/or vasopressin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin and/or vasopressin, including preterm labor, premature birth, dysmenorrhea, inappropriate secretion of vasopressin, congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome and ocular hypertension. The present invention is furthermore related to novel sulfanilide derivatives as well as to methods of their preparation.

  本发明涉及式(I)的磺胺基苯酰胺衍生物，其中R1和R2是可选择取代的芳基和杂环芳基基团，其他变量如权利要求中所定义，用作药用活性化合物，以及含有这种磺胺基苯酰胺衍生物的药物配方。所述衍生物在治疗和/或预防早产、早产、痛经、抗利尿素分泌不当、充血性心力衰竭、动脉高血压、肝硬化、肾病综合征和眼压增高方面具有用途。具体而言，本发明涉及显示对催产素和/或抗利尿素受体具有显著调节作用，特别是拮抗活性的磺胺基苯酰胺衍生物。更具体地说，所述化合物在治疗和/或预防由催产素和/或抗利尿素介导的疾病状态方面具有用途，包括早产、早产、痛经、抗利尿素分泌不当、充血性心力衰竭、动脉高血压、肝硬化、肾病综合征和眼压增高。本发明还涉及新型磺胺基苯酰胺衍生物以及其制备方法。
• [EN] PHARMACEUTICALLY ACTIVE SULFANILIDE DERIVATIVES<br/>[FR] DERIVES DE SULFANILIDE ACTIFS DU POINT DE VUE PHARMACEUTIQUE
  申请人：APPLIED RESEARCH SYSTEMS

  公开号：WO2002032864A1

  公开（公告）日：2002-04-25

  The present invention relates to sulfanilide derivatives of formula (I), in which R?1 and R2¿ are optionally substituted aryl and heteroaryl groups and the other variables are as defined in the claims, for use as pharmaceutically active compounds, as well as pharmaceutical formulations containing such sulfanilide derivatives. Said derivatives are useful in the treatment and/or prevention of preterm labor, premature birth, dysmenorrhea, inappropriate secretion of vasopressin, congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome and ocular hypertension. In particular, the present invention is related to sulfanilide derivatives displaying a substantial modulatory, in particular antagonistic activity, of the oxytocin and/or vasopressin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin and/or vasopressin, including preterm labor, premature birth, dysmenorrhea, inappropriate secretion of vasopressin, congestive heart failure, arterial hypertension, liver cirrhosis, nephrotic syndrome and ocular hypertension. The present invention is furthermore related to novel sulfanilide derivatives as well as to methods of their preparation.

  本发明涉及公式（I）的磺胺基苯酰亚胺衍生物，其中R1和R2是可选取代的芳基和杂环芳基基团，其他变量如权利要求所定义，用作药物活性化合物，以及含有这种磺胺基苯酰亚胺衍生物的药物配方。所述衍生物在治疗和/或预防早产、早产、痛经、抗利尿激素不当分泌、充血性心力衰竭、动脉高血压、肝硬化、肾病综合征和眼压增高方面有用。特别是，本发明涉及显示 oxytocin 和/或 vasopressin 受体的实质性调节活性，特别是拮抗活性的磺胺基苯酰亚胺衍生物。更好地，这些化合物在治疗和/或预防由 oxytocin 和/或 vasopressin 介导的疾病状态方面有用，包括早产、早产、痛经、抗利尿激素不当分泌、充血性心力衰竭、动脉高血压、肝硬化、肾病综合征和眼压增高。本发明还涉及新的磺胺基苯酰亚胺衍生物以及它们的制备方法。
• PHARMACEUTICALLY ACTIVE SULFANILIDE DERIVATIVES
  申请人：Applied Research Systems ARS Holding N.V.

  公开号：EP1335901A1

  公开（公告）日：2003-08-20
• US7312358B2
  申请人：——

  公开号：US7312358B2

  公开（公告）日：2007-12-25
• Discovery and Development of a New Class of Potent, Selective, Orally Active Oxytocin Receptor Antagonists
  作者：Anna Quattropani、Jérôme Dorbais、David Covini、Pierre-André Pittet、Véronique Colovray、Russell J. Thomas、Richard Coxhead、Serge Halazy、Alexander Scheer、Marc Missotten、Guidon Ayala、Charles Bradshaw、Anne-Marie De Raemy-Schenk、Anthony Nichols、Rocco Cirillo、Enrico Gillio Tos、Claudio Giachetti、Lucia Golzio、Paolo Marinelli、Dennis J. Church、Claude Barberis、André Chollet、Matthias K. Schwarz

  DOI：10.1021/jm050645f

  日期：2005.12.1

  We report a novel chemical class of potent oxytocin receptor antagonists showing a high degree of selectivity against the closely related vasopressin receptors (V1a, V1b, V2). An initial compound, 7, was shown to be active in an animal model of preterm labor when administered by the intravenous but not by the oral route. Stepwise SAR investigations around the different structural elements revealed

  我们报告了一种新型的强力催产素受体拮抗剂的化学类别，它显示了对紧密相关的加压素受体（V1a，V1b，V2）的高度选择性。当通过静脉内而非口服途径给药时，最初的化合物7在早产的动物模型中显示出活性。围绕不同结构元件进行的逐步SAR研究表明，一个位置即芳烃磺酰基部分易于改变结构。因此，该位置用于引入各种取代基以改善物理化学性质。发现一些所得的类似物在体外效力和水溶性方面均优于7，这转化为在静脉内和口服施用后在动物模型中的功效显着改善。最好的化合物73