methyl 2-chloro-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylate | 125341-30-2

• 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: methyl 2-chloro-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylate
• CAS: 125341-30-2
• 化学式: C₁₄H₁₅ClO₃
• 分子量: 266.724
• InChiKey: IZQIDQOCRNKVLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-chloro-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 2-chloro-cis-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
• 作为产物：
  描述：

  methyl 5-chloro-3-(3'-cyclohexenyl)salicylate 在 三氟乙酸 作用下， 生成 methyl 2-chloro-5a,6,7,8,9,9a-hexahydrodibenzofuran-4-carboxylate
  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

• 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.

  该发明涉及某些二苯并呋喃羧酰胺及其用作5HT.sub.3拮抗剂的应用，具有独特的中枢神经系统、抗恶心和胃动力活性，不具有任何显著的D.sub.2受体结合特性。该发明还描述了其制备所需的新型工艺。
• 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, their use as pharmaceutical agents, a composition containing the same, and a process for the preparation thereof
  申请人：RHONE-POULENC RORER INTERNATIONAL (HOLDINGS) INC.

  公开号：EP0339950A2

  公开（公告）日：1989-11-02

  This invention provides certain dibenzofurancar­boxamides as defined by the formula: where R₁ is hydrogen, amino, alkylamino or halo; R₂ is hydrogen, halo, sulfamyl, alkylsulfamyl or alkylsulfonyl; R′ is hydrogen or alkyl or together with a vicinal R′ group may form a double bond; and R is certain specific nitrogen heterocyclic groups. The compounds of the invention are useful as 5HT₃ antagonists having unique CNS, anti-emetic and gastric prokinetic activity void of any significant D₂ receptor binding properties. The invention also provides processes necessary for the preparation of the compounds of the invention.

  本发明提供了某些由式定义的二苯并呋喃甲酰胺： 其中 R₁ 是氢、氨基、烷基氨基或卤素； R₂ 是氢、卤素、氨基磺酰基、烷基氨基磺酰基或烷基磺酰基； R′ 是氢或烷基，或与邻接的 R′基团一起可形成双键；以及 R 是某些特定的氮杂环基团。 本发明化合物可作为 5HT₃ 拮抗剂，具有独特的中枢神经系统、止吐和促胃动力活性，不具有任何明显的 D₂ 受体结合特性。本发明还提供了制备本发明化合物的必要工艺。
• J. Med. Chem. 1992, 35, 903-911
  作者：

  DOI：——

  日期：——