1-benzo[1,3]dioxol-5-ylmethyl-3-(3-methoxy-phenylsulfanyl)-1H-indole-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-benzo[1,3]dioxol-5-ylmethyl-3-(3-methoxy-phenylsulfanyl)-1H-indole-2-carboxylic acid
• 英文别名: 1-(1,3-benzodioxol-5-ylmethyl)-3-(3-methoxyphenyl)sulfanylindole-2-carboxylic acid
• 化学式: C₂₄H₁₉NO₅S
• 分子量: 433.485
• InChiKey: KEJQXHVQMSWRIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  胡椒基氯 在 lithium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-benzo[1,3]dioxol-5-ylmethyl-3-(3-methoxy-phenylsulfanyl)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  1-benzyl-3-thioaryl-2-carboxyindoles as potent non-peptide endothelin antagonists

  摘要：

  Endothelin-1 is a potent vasoconstrictor which is thought to be involved in many human disease states. We have developed a series of indole non-peptide endothelin antagonists which display nanomolar receptor affinity. The representative compound from this series is PD 159433 (22), an ET(A) selective antagonist with an IC50 of 2 nM. The discovery, synthesis and structure-activity relationships of this series of compounds are described. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00232-6

文献信息

• Combinations of an endothelin receptor antagonist and an antiepileptic compound having pain alleviating properties or analgesic
  申请人：——

  公开号：US20030232787A1

  公开（公告）日：2003-12-18

  The present invention is a novel combination effective for alleviating pain comprising a pain alleviating effective amount of an endothelin receptor antagonist or a pharmaceutically acceptable salt thereof and from 1 to 3 compounds independently selected from the group consisting of antiepileptic compounds having pain alleviating properties and analgesics, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising same. The administration of endothelin receptor antagonists in these novel combinations results in an improved reduction in the frequency and severity of pain. The incidence of unwanted side effects can be reduced by these novel combinations in comparison to using higher doses of a single agent treatment to achieve a similar therapeutic effect. The present invention is also directed to methods of using effective amounts of the novel combinations and pharmaceutical compositions thereof to treat pain in mammals, including a human.

  本发明是一种有效缓解疼痛的新型复方制剂，它包含缓解疼痛有效量的内皮素受体拮抗剂或其药学上可接受的盐，以及1至3种独立选自具有缓解疼痛特性的抗癫痫化合物和镇痛剂及其药学上可接受的盐组成的化合物，以及包含这些化合物的药物组合物。在这些新型组合物中施用内皮素受体拮抗剂，可有效降低疼痛的频率和严重程度。与使用较大剂量的单药治疗以达到类似的治疗效果相比，这些新型组合物可以降低不希望出现的副作用的发生率。本发明还涉及使用有效量的新型组合物及其药物组合物治疗哺乳动物（包括人类）疼痛的方法。
• NONPEPTIDE ENDOTHELIN ANTAGONISTS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0790993A1

  公开（公告）日：1997-08-27
• COMBINATIONS OF AN ENDOTHELIN RECEPTOR ANTAGONIST AND AN ANTIEPILEPTIC COMPOUND HAVING PAIN ALLEVIATING PROPERTIES OR ANALGESIC
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1289558A2

  公开（公告）日：2003-03-12
• US5482960A
  申请人：——

  公开号：US5482960A

  公开（公告）日：1996-01-09
• [EN] NONPEPTIDE ENDOTHELIN ANTAGONISTS<br/>[FR] ANTAGONISTES NON PEPTIDIQUES DE L'ENDOTHELINE
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1996015125A1

  公开（公告）日：1996-05-23

  (EN) Modified nonpeptide antagonists of endothelin of formula (I), wherein Rc is S(O)p-phenyl, which are useful in treating elevated levels of endothelin, essential renovascular malignant and pulmonary hypertension, cerebral infarction, cerebral ischemia, congestive heart failure and subarachnoid hemorrhage.(FR) Antagonistes non peptidiques modifiés de l'endothéline de la formule (I), dans laquelle Rc représente S(O)p-phényle. Ces antagonistes sont utiles pour traiter des affections associées à des niveaux élevés d'endothéline, en particulier l'hypertension essentielle réno-vasculaire, artérielle et pulmonaire, l'infarctus cérébral, l'ischémie cérébrale, l'insuffisance cardiaque congestive et l'hémorragie sous-arachnoïdienne.