2-chloro-(5aR,9aR)-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylic acid | 1243343-39-6

• 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: 2-chloro-(5aR,9aR)-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylic acid
• 英文别名: 2-Chloro-cis-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylic acid；(5aR,9aR)-2-chloro-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylic acid
• CAS: 1243343-39-6
• 化学式: C₁₃H₁₃ClO₃
• 分子量: 252.697
• InChiKey: KGDVUOOBBADURR-LDYMZIIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-(5aR,9aR)-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylic acid 在 氯化亚砜 作用下， 以 氯仿 为溶剂， 反应 0.75h， 生成 (5aS,9aS)-2-Chloro-5a,6,7,8,9,9a-hexahydro-dibenzofuran-4-carbonyl chloride
  参考文献：
  名称：

  Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides

  摘要：

  Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog. The absolute configuration of the most active molecules 10 and 18 have been determined by X-ray crystallography. These two compounds are more potent than known 5-HT3 receptor antagonists both in vivo and in vitro in blocking 5-HT3 receptor activation and preventing chemotherapeutic induced emesis. Compared with 5-HT3 antagonists, such as GR 38032F, zacopride, BRL 43694, and ICS 205-930, compound 10 was more potent in (1) inhibiting binding to 5-HT3 receptor binding sites in rat cortex (K(i) = 0.17 nM), (2) blocking the von Bezold-Jarisch effect in the rat (lowest effective dose, 1-mu-g/kg iv), and (3) inhibiting 5-HT-induced contraction of guinea pig ileum (lowest effective concentration, 10(-9) M). This novel agent was as effective given po as when given iv in reducing cisplatin-induced emetic episodes in the ferret (ED50 = 4-mu-g/kg iv or po). A 1 mg/kg po dose of 10 virtually abolished cisplatin-induced emesis for 10 h in the ferret. However, it was inactive against apomorphine or copper sulfate-induced vomiting. These data, coupled with receptor binding studies of ligands for D2-dopamine, a1, a2, 5-HT1, 5-HT2, and muscarinic receptors demonstrate that 10 is a highly selective 5-HT3 receptor antagonist with remarkable potency in vivo.

  DOI：

  10.1021/jm00083a015
• 作为产物：
  描述：

  2-chloro-cis-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylic acid 生成 2-chloro-(5aR,9aR)-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylic acid
  参考文献：
  名称：

  Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides

  摘要：

  Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog. The absolute configuration of the most active molecules 10 and 18 have been determined by X-ray crystallography. These two compounds are more potent than known 5-HT3 receptor antagonists both in vivo and in vitro in blocking 5-HT3 receptor activation and preventing chemotherapeutic induced emesis. Compared with 5-HT3 antagonists, such as GR 38032F, zacopride, BRL 43694, and ICS 205-930, compound 10 was more potent in (1) inhibiting binding to 5-HT3 receptor binding sites in rat cortex (K(i) = 0.17 nM), (2) blocking the von Bezold-Jarisch effect in the rat (lowest effective dose, 1-mu-g/kg iv), and (3) inhibiting 5-HT-induced contraction of guinea pig ileum (lowest effective concentration, 10(-9) M). This novel agent was as effective given po as when given iv in reducing cisplatin-induced emetic episodes in the ferret (ED50 = 4-mu-g/kg iv or po). A 1 mg/kg po dose of 10 virtually abolished cisplatin-induced emesis for 10 h in the ferret. However, it was inactive against apomorphine or copper sulfate-induced vomiting. These data, coupled with receptor binding studies of ligands for D2-dopamine, a1, a2, 5-HT1, 5-HT2, and muscarinic receptors demonstrate that 10 is a highly selective 5-HT3 receptor antagonist with remarkable potency in vivo.

  DOI：

  10.1021/jm00083a015

文献信息

• Hexahydrodibenzofuran carboxylic acid derivatives
  申请人：Rorer Pharmaceutical Corporation

  公开号：US04959485A1

  公开（公告）日：1990-09-25

  This invention is directed to certain dibenzofurancarboxamides and their use as 5HT.sub.3 antagonists having unique CNS, anti-emetic and gastric prokinetic activity void of any significant D.sub.2 receptor binding properties. This invention also describes novel processes necessary for their preparation.

  本发明涉及某些二苯并呋喃羧酰胺及其用作5HT.sub.3拮抗剂，具有独特的中枢神经系统、抗恶心和胃动力促进活性，不具有任何显著的D.sub.2受体结合性质。本发明还描述了其制备所必需的新型工艺。
• Pharmaceutically useful dibenzofurancarboxamides of specific
  申请人：Rhone-Poulenc Rorer Pharmaceuticals Inc.

  公开号：US05246942A1

  公开（公告）日：1993-09-21

  This invention is directed to certain dibenzofurancarboxamides and their use as 5HT.sub.3 antagonists having unique CNS, anti-emetic and gastric prokinctic activity void of any significant D.sub.2 receptor binding properties. This invention also describes novel processes necessary for their preparation.

  本发明涉及某些二苯并呋喃羧酰胺及其作为5HT.sub.3拮抗剂的应用，具有独特的中枢神经系统、抗恶心和胃促动力活性，且不具有任何显著的D.sub.2受体结合特性。本发明还描述了其制备所必需的新型工艺。
• Dibenzofurancarboxamides and their pharmaceutical compositions and
  申请人：Rorer Pharmaceutical Corporation

  公开号：US04863921A1

  公开（公告）日：1989-09-05

  This invention is directed to certain dibenzofurancarboxamides and their use as 5HT.sub.3 antagonists having unique CNS, anti-emetic and gastric prokinetic activity void of any significant D.sub.2 receptor binding properties. This invention also describes novel processes necessary for their preparation.

  本发明涉及某些二苯并呋喃羧酰胺及其作为5HT.sub.3拮抗剂的应用，具有独特的中枢神经系统、抗恶心和胃运动促进活性，不具有任何显著的D.sub.2受体结合特性。本发明还描述了其制备所需的新型工艺。
• YOUSSEFYEH, RAYMOND D.;CAMPBELL, HEURY F.;KUHLA, DONALD E.
  作者：YOUSSEFYEH, RAYMOND D.、CAMPBELL, HEURY F.、KUHLA, DONALD E.

  DOI：——

  日期：——
• US5246942A
  申请人：——

  公开号：US5246942A

  公开（公告）日：1993-09-21