3-Ethyl-3-(3-hydroxy-phenyl)-azepane-1-carboxylic acid ethyl ester | 27185-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: 3-Ethyl-3-(3-hydroxy-phenyl)-azepane-1-carboxylic acid ethyl ester
• 英文别名: Ethyl 3-ethyl-3-(3-hydroxyphenyl)azepane-1-carboxylate
• CAS: 27185-01-9
• 化学式: C₁₇H₂₅NO₃
• 分子量: 291.39
• InChiKey: SMOPDNPETOQKOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Ethyl-3-(3-hydroxy-phenyl)-azepane-1-carboxylic acid ethyl ester 在 氢溴酸 作用下， 以 水 为溶剂， 生成 3-(3-ethylhexahydro<1H>azepine-3-yl)phenol hydrobromide
  参考文献：
  名称：

  NOVEL CARBAMATE AMINO ACID AND PEPTIDE PRODRUGS OF OPIOIDS AND USES THEREOF

  摘要：

  本发明提供了与咪哌唑酮和其他阿片类镇痛剂相关的氨基甲酸酯前药。前药基团可以包括单个氨基酸或短肽。此外，本发明涉及减少受试者胃肠道副作用的方法，其中胃肠道副作用与阿片类镇痛剂的给药有关。该方法包括口服给受试者阿片类前药或其药学上可接受的盐，其中阿片类前药由阿片类镇痛剂通过氨基甲酸酯键共价结合到前药基团上，且在口服给药时，前药或药学上可接受的盐至少减少与单独口服阿片类镇痛剂有关的一个胃肠道副作用。本发明还提供了用于该方法的组合物。

  公开号：

  US20110015182A1
• 作为产物：
  描述：

  Ethyl 3-(3-ethoxycarbonyloxyphenyl)-3-ethylazepane-1-carboxylate 在 水 、 sodium hydroxide 作用下， 生成 3-Ethyl-3-(3-hydroxy-phenyl)-azepane-1-carboxylic acid ethyl ester
  参考文献：
  名称：

  NOVEL CARBAMATE AMINO ACID AND PEPTIDE PRODRUGS OF OPIOIDS AND USES THEREOF

  摘要：

  本发明提供了与咪哌唑酮和其他阿片类镇痛剂相关的氨基甲酸酯前药。前药基团可以包括单个氨基酸或短肽。此外，本发明涉及减少受试者胃肠道副作用的方法，其中胃肠道副作用与阿片类镇痛剂的给药有关。该方法包括口服给受试者阿片类前药或其药学上可接受的盐，其中阿片类前药由阿片类镇痛剂通过氨基甲酸酯键共价结合到前药基团上，且在口服给药时，前药或药学上可接受的盐至少减少与单独口服阿片类镇痛剂有关的一个胃肠道副作用。本发明还提供了用于该方法的组合物。

  公开号：

  US20110015182A1

文献信息

• Asymmetric Total Synthesis of Meptazinol
  作者：Tobias Babl、Oliver Reiser

  DOI：10.1021/acs.joc.2c00272

  日期：2022.5.6

  The first enantioselective synthesis of (S)-meptazinol in 14 steps from commercially available ethyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate, being widely used in racemic form for pain treatment, and, en route, the formal synthesis of two anti-Alzheimer’s agents are reported. A novel ring expansion of 2-azabicyclo[4.1.0]heptanes, readily available via the stereoselective cyclopropanation of 1,2,3

  首次从市售的 4-oxo-3,4-dihydropyridine-1( 2H )-羧酸乙酯分 14 个步骤选择性合成 ( S )-meeptazinol ，广泛用于外消旋形式的疼痛治疗，并且在途中，报道了两种抗阿尔茨海默病药物的正式合成。通过 1,2,3,4-四氢吡啶-4-醇的立体选择性环丙烷化很容易获得 2-氮杂双环 [4.1.0] 庚烷的新型扩环，为 3,3-二取代氮杂环戊烷提供了有效的途径，代表了多种获批药物的核心。
• NOVEL DICARBOXYLIC ACID LINKED AMINO ACID AND PEPTIDE PRODRUGS OF OPIOIDS AND USES THEREOF
  申请人：Franklin Richard

  公开号：US20100286186A1

  公开（公告）日：2010-11-11

  The present invention concerns dicarboxylic acid linked amino acid and peptide prodrugs of opioid analgesics and pharmaceutical compositions containing such prodrugs. Methods for providing pain relief, decreasing the adverse GI side effects of the opioid analgesic and increasing the bioavailability of the opioid analgesic with the aforementioned prodrugs are also provided. In one embodiment, prodrugs having the amino acid side chains of valine, leucine, isoleucine and glycine; and mono-, di- and tripeptides thereof are provided.
• NOVEL CARBAMATE AMINO ACID AND PEPTIDE PRODRUGS OF OPIATES AND USES THEREOF
  申请人：Franklin Richard

  公开号：US20120270847A1

  公开（公告）日：2012-10-25

  Carbamate linked prodrugs of meptazinol and other opioid analgesics are provided. The prodrug moiety may comprise a single amino acid or short peptide. Additionally, the present invention relates to methods for reducing gastrointestinal side effects in a subject, the gastrointestinal side effects being associated with the administration of an opioid analgesic. The methods comprise orally administering an opioid prodrug or pharmaceutically acceptable salt thereof to a subject, wherein the opioid pro-drug is comprised of an opioid analgesic covalently bonded through a carbamate linkage to a prodrug moiety, and wherein upon oral administration, the prodrug or pharmaceutically acceptable salt minimizes at least one gastrointestinal side effect associated with oral administration of the opioid analgesic alone. Compositions for use with the method are also provided.
• [EN] NOVEL DICARBOXYLIC ACID LINKED AMINO ACID AND PEPTIDE PRODRUGS OF OPIOIDS AND USES THEREOF<br/>[FR] NOUVEAUX PROMÉDICAMENTS D'OPIOÏDES À BASE D'ACIDE AMINÉ ET DE PEPTIDE LIÉS À L'ACIDE DICARBOXYLIQUE ET LEURS UTILISATIONS
  申请人：SHIRE LLC

  公开号：WO2010112942A1

  公开（公告）日：2010-10-07

  The present invention concerns dicarboxylic acid linked amino acid and peptide prodrugs of opioid analgesics and pharmaceutical compositions containing such prodrugs. Methods for providing pain relief, decreasing the adverse GI side effects of the opioid analgesic and increasing the bioavailability of the opioid analgesic with the aforementioned prodrugs are also provided. In one embodiment, prodrugs having the amino acid side chains of valine, leucine, isoleucine and glycine; and mono–, di–and tripeptides thereof are provided.
• [EN] NOVEL CARBAMATE AMINO ACID AND PEPTIDE PRODRUGS OF OPIOIDS AND USES THEREOF<br/>[FR] NOUVEL ACIDE AMINE DE CARBAMATE ET PROMEDICAMENTS PEPTIDIQUES D'OPIOÏDES, ET UTILISATIONS ASSOCIEES
  申请人：SHIRE LLC

  公开号：WO2011007247A1

  公开（公告）日：2011-01-20

  Carbamate linked prodrugs of meptazinol and other opioid analgesics are provided. The prodrug moiety may comprise a single amino acid or short peptide. Additionally, the present invention relates to methods for reducing gastrointestinal side effects in a subject, the gastrointestinal side effects being associated with the administration of an opioid analgesic. The methods comprise orally administering an opioid prodrug or pharmaceutically acceptable salt thereof to a subject, wherein the opioid prodrug is comprised of an opioid analgesic covalently bonded through a carbamate linkage to a prodrug moiety, and wherein upon oral administration, the prodrug or pharmaceutically acceptable salt minimizes at least one gastrointestinal side effect associated with oral administration of the opioid analgesic alone. Compositions for use with the method are also provided.