1,8-二乙基-1,3,4,9-四氢-1-甲基吡喃并[3,4-b]吲哚 | 115066-03-0

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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
• 中文名称: 1,8-二乙基-1,3,4,9-四氢-1-甲基吡喃并[3,4-b]吲哚
• 英文名称: 1,8-diethyl-1-methyl-1,3,4,9-tetrahydropyrano-<3,4-b>indole
• 英文别名: 1,8-diethyl-1-methyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole；1,8-Diethyl-1,3,4,9-tetrahydropyrano(3,4-b)indole；1,8-diethyl-1-methyl-4,9-dihydro-3H-pyrano[3,4-b]indole
• CAS: 115066-03-0
• 化学式: C₁₆H₂₁NO
• 分子量: 243.349
• InChiKey: IYMCQNNWNNRAQH-UHFFFAOYSA-N

物化性质

• 沸点：
  390.2±37.0 °C(Predicted)
• 密度：
  1.064±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

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：
  25
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,8-二乙基-1,3,4,9-四氢-1-甲基吡喃并[3,4-b]吲哚 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 7-乙基-3-羟乙基吲哚
  参考文献：
  名称：

  水溶液中依托度酸降解的动力学和机理。

  摘要：

  依托度酸（1; 1,8-二乙基-1,3,4,9-四氢吡喃并[3,4-b]-吲哚-1-乙酸）的分解程度和机理是pH和温度的函数调查。衍生自1的三种主要降解产物被鉴定为7-乙基-2-（1-亚甲基丙基）-1H-吲哚-3-乙醇（2），依托度酸的脱羧产物（3）和7-乙基色酚（4）。降解1的主要途径是连续的一级动力学：在平衡3 ---- 4中为1 ---- 2。对于本研究中的任何一种缓冲液，均未观察到对1降解有明显的缓冲作用。速率-pH曲线在酸性（kH）和中性（k'H）pH区域表现出特定的酸催化作用，在pH 4.65处的拐点对应于pKa值。从Arrhenius曲线图中，kH和k'的活化能（Ea）发现H分别为26和24kcal / mol。较小的活化正熵（δS）表明单分子分解机理有利于1的分解反应。

  DOI：

  10.1002/jps.2600770116
• 作为产物：
  描述：

  甲醇 、 依托度酸 在 硫酸 作用下， 反应 72.0h， 生成 依托度酸甲酯 、 1,8-二乙基-1,3,4,9-四氢-1-甲基吡喃并[3,4-b]吲哚
  参考文献：
  名称：

  A Scaleable Combined Resolution and Improved Dosage Form for Etodolac with Recycle of the Off-Isomer

  摘要：

  An efficient resolution process using N-methyl glucamine (meglumine) which directly provides (S)-etodolac as the meglumine salt is described. This salt is also a dosage form with improved absorption characteristics. The off-isomer is efficiently racemised via the ester, prepared by mild esterification, followed by hydrolysis affording rac-etodolac suitable for recycling.

  DOI：

  10.1021/op000014p

文献信息

• COMPOSITIONS AND METHODS TO PREVENT TOXICITY INDUCED BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS
  申请人：GARVEY David S.

  公开号：US20080275010A1

  公开（公告）日：2008-11-06

  Nonsteroidal antiinflammatory drugs which have been substituted with a nitrogen monoxide group; compositions comprising (i) a nonsteroidal antiinflammatory drug, which can optionally be substituted with a nitrogen monoxide group and (ii) a compound that directly donates, transfers or releases a nitrogen monoxide group (preferably as a charged species, particularly nitrosonium); and methods of treatment of inflammation, pain, gastrointestinal lesions and/or fever using the compositions are disclosed. The compounds and compositions protect against the gastrointestinal, renal and other toxicities that are otherwise induced by nonsteroidal antiinflammatory drugs.

  本发明涉及已被替换为氮单氧化物基团的非甾体抗炎药；包括（i）非甾体抗炎药，可选择性地被替换为氮单氧化物基团和（ii）直接捐赠、转移或释放氮单氧化物基团的化合物（优选为带电物种，特别是亚硝酸盐）的组合物；以及使用这些组合物治疗炎症、疼痛、胃肠道损伤和/或发热的方法。这些化合物和组合物可以保护免受非甾体抗炎药引起的胃肠道、肾脏和其他毒性的影响。
• NITROSATED NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：EARL Richard A.

  公开号：US20100093671A1

  公开（公告）日：2010-04-15

  The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

  该发明描述了新型亚硝酰化非甾体抗炎药（NSAIDs）及其药学上可接受的盐，并且描述了至少包含一种亚硝酰化NSAID和可选的至少一种化合物的新型组合物，该化合物捐赠、转移或释放一氧化氮，刺激内源性一氧化氮的合成，提高内源性内皮源性松弛因子的水平或是一氧化氮合酶的底物，并/或至少包含一种治疗剂。该发明还提供了至少包含一种亚硝酰化NSAID和至少一种化合物的新型组合物，该化合物捐赠、转移或释放一氧化氮，提高内源性内皮源性松弛因子的水平，刺激内源性一氧化氮的合成或是一氧化氮合酶的底物，并/或至少包含一种治疗剂。该发明还提供了至少包含一种亚硝酰化NSAID，可选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。该发明还提供了治疗炎症、疼痛和发热的方法；治疗胃肠道疾病的方法；促进伤口愈合的方法；治疗和/或预防使用非甾体抗炎化合物导致的胃肠道、肾脏和/或呼吸道毒性的方法；治疗炎症性疾病状态和/或疾病的方法；以及治疗和/或预防眼科疾病和/或疾病的方法。
• Nitrosated Nonsteroidal Antiinflammatory Compounds, Compositions and Methods of Use
  申请人：Earl Richard

  公开号：US20110098253A1

  公开（公告）日：2011-04-28

  The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders comprising administration of novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent.

  该发明还提供了治疗炎症、疼痛和发热的方法；治疗胃肠道疾病的方法；促进伤口愈合的方法；治疗和/或预防非甾体类抗炎化合物使用引起的胃肠道、肾脏和/或呼吸道毒性的方法；治疗炎症性疾病状态和/或疾病的方法；以及治疗和/或预防眼科疾病和/或疾病的新组合物的给药方法，该组合物包括至少一种硝化的非甾体类抗炎药，以及可选地至少一种捐赠、转移或释放一氧化氮、提高内皮源性松弛因子内源水平、刺激内源性一氧化氮合成或是一氧化氮合酶底物和/或至少一种治疗剂。
• ANTI-INFLAMMATORY ANALGESIC FOR EXTERNAL USE
  申请人：Medrx Co., Ltd.

  公开号：EP1716868B1

  公开（公告）日：2011-11-23
• ORGANIC NITRIC OXIDE DONOR SALTS OF NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：Garvey David S.

  公开号：US20090048219A1

  公开（公告）日：2009-02-19

  The invention describes novel organic nitric oxide enhancing salts of nonsteroidal antiinflammatory drugs (NSAIDs) and novel compositions comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one organic nitric oxide enhancing salt of an NSAID, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating inflammation, pain and fever; (b) treating gastrointestinal disorders; (c) facilitating wound healing; (d) treating gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; (e) treating inflammatory disease states and/or disorders; (f) treating ophthalmic disorders; (h) treating peripheral vascular diseases; (i) treating diseases resulting from oxidative stress; (j) treating endothelial dysfunctions; and (k) treating diseases caused by endothelial dysfunctions. The organic nitric oxide enhancing compounds that form salts with the NSAIDs are organic nitrates, organic nitrites, nitrosothiols, thionitrites, thionitrates, NONOates, heterocyclic nitric oxide donors and/or nitroxides. The heterocyclic nitric oxide donors are furoxans, sydnonimines, oxatriazole-5-ones and/or oxatriazole-5-imines.