1,3-dioxo-isoindoline-2-carboxylic acid amide | 344413-31-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1,3-dioxo-isoindoline-2-carboxylic acid amide
• 英文别名: 1,3-Dioxo-isoindolin-2-carbonsaeure-amid；phthalimido carboxamide；1,3-dioxoisoindole-2-carboxamide
• CAS: 344413-31-6
• 化学式: C₉H₆N₂O₃
• 分子量: 190.158
• InChiKey: LAFRKWDMWGHGPG-UHFFFAOYSA-N

物化性质

• 熔点：
  196-198 °C
• 沸点：
  397.9±25.0 °C(Predicted)
• 密度：
  1.571±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3-dioxo-isoindoline-2-carboxylic acid amide 在 三氟乙酸 作用下， 反应 0.5h， 生成 N-(5-fluoro-2-oxo-2,3-dihydro-1-benzofuran-3-yl)-1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxamide
  参考文献：
  名称：

  带有尿素亚结构的高化学发光苯并[b]呋喃-2（3H）-酮的首次合成

  摘要：

  一系列带有脲亚结构的苯并[ b ]呋喃-2（3 H）-ones（coumaran-2-ones），即3-（氨基羰基氨基）苯并[ b ]呋喃-2（3 H）-one的衍生物，是第一次准备。这些化合物在关键步骤中通过酚类的亲电α氨基烷基化方法（Tscherniac-Einhorn反应）的可及性以及所需化合物的化学发光（CL）性能在很大程度上取决于尿素部分的取代方式。讨论了竞争性的反应途径，并提出了一种具有普遍意义的改进的一锅法合成方法。总之，尤其是N，苯并[ b ]呋喃-2（3 H）-的N-二烷基氨基羰基氨基衍生物在用1,8-二氮杂双环[5.4.0]十一碳-7-烯（DBU）处理后表现出强烈的闪光，如蓝色CL在氧气或过氧化氢的存在下。比较的物理化学研究表明，就CL强度和衰变速度而言，新化合物的性能优于其氨基甲酸酯类似物，这使其有可能在短时间内用作基于CL的新工具。

  DOI：

  10.1002/hlca.201800243
• 作为产物：
  描述：

  N-carbamoyl-phthalamic acid 、 三氯氧磷 生成 1,3-dioxo-isoindoline-2-carboxylic acid amide
  参考文献：
  名称：

  Die Konstitution des Phthalylharnstoffs

  摘要：

  DOI：

  10.1007/bf02158324

文献信息

• [EN] MULTICYCLIC PEPTIDES AND METHODS FOR THEIR PREPARATION<br/>[FR] PEPTIDES MULTICYCLIQUES ET LEURS PROCÉDÉS DE PRÉPARATION
  申请人：STICHTING TECHNISCHE WETENSCHAPPEN

  公开号：WO2018106112A1

  公开（公告）日：2018-06-14

  The invention relates to methods for preparing a compound comprising a peptide attached to a molecular scaffold whereby multiple peptide loops are formed, to compounds that can be obtained with such methods and uses thereof.

  这项发明涉及制备一种包括肽附着在分子支架上的化合物的方法，从而形成多个肽环，以及可以通过这些方法获得的化合物及其用途。
• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL CONDITIONS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT D'AFFECTIONS NEUROLOGIQUES
  申请人：KANDULA MAHESH

  公开号：WO2013168002A1

  公开（公告）日：2013-11-14

  The invention relates to the compounds of formula (I) or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula (I), and methods for the treatment of neurological conditions may he formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may he used to treatment: of fibromyalgia, depression, neuropathic pain, severe pain, chronic pain, generalized pain, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multipie sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, post herpetic neuralgia, diabetic neuropathy, cancer pain, fibromyalgia and lower back pain.

  该发明涉及公式(I)的化合物或其药用可接受的盐，以及其多晶型、溶剂合物、对映体、立体异构体和水合物。包括有效量的公式(I)化合物的药物组合物，以及用于治疗神经系统疾病的方法可以制备用于口服、颊粘膜、直肠、局部、经皮、经粘膜、静脉、肠道、糖浆或注射的制剂。这些组合物可用于治疗：纤维肌痛、抑郁症、神经病性疼痛、严重疼痛、慢性疼痛、全身性疼痛、损伤、术后疼痛、骨关节炎、类风湿性关节炎、多发性硬化、脊髓损伤、偏头痛、HIV相关神经病性疼痛、带状疱疹后神经痛、糖尿病性神经病变、癌症疼痛、纤维肌痛和腰背痛。
• COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL CONDITIONS
  申请人：Kandula Mahesh

  公开号：US20150119452A1

  公开（公告）日：2015-04-30

  The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of neurological conditions may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of fibromyalgia, depression, neuropathic pain, severe pain, chronic pain, generalized pain, injury, post-operative pain, osteoarthritis, rheumatoid arthritis, multiple sclerosis, spinal cord injury, migraine, HIV related neuropathic pain, post herpetic neuralgia, diabetic neuropathy, cancer pain, fibromyalgia and lower back pain.

  本发明涉及化合物I的公式或其药用可接受的盐，以及其多型、溶剂合物、对映体、立体异构体和水合物。包含化合物I的有效量的药物组合物，以及用于治疗神经系统疾病的方法可以制成口服、颊内、直肠、局部、经皮、经粘膜、静脉、肠道、糖浆或注射剂形式。这种组合物可以用于治疗纤维肌痛、抑郁症、神经病性疼痛、严重疼痛、慢性疼痛、全身疼痛、损伤、术后疼痛、骨关节炎、类风湿性关节炎、多发性硬化、脊髓损伤、偏头痛、HIV相关神经病性疼痛、带状疱疹后神经痛、糖尿病性神经病、癌症疼痛、纤维肌痛和腰背痛的治疗。
• [EN] METHOD FOR SYNTHESIS OF (1S, 2R)-MILNACIPRAN<br/>[FR] PROCÉDÉ POUR LA SYNTHÈSE DE (1S,2R)-MILNACIPRAN
  申请人：PF MEDICAMENT

  公开号：WO2010086394A1

  公开（公告）日：2010-08-05

  The present invention relates to a method for synthesizing a pharmaceutically acceptable acid addition salt of (1S, 2R)-milnacipran comprising the following successive steps: (a) reaction of phenylacetonitrile and of (R)-epichlorhydrin in the presence of a base containing an alkaline metal, followed by a basic treatment, and then by an acid treatment in order to obtain a lactone; (b) reaction of said lactone with MNEt2, wherein M represents an alkaline metal, or with NHEt2 in the presence of a Lewis acid-amine complex, in order to obtain an amide-alcohol; (c) reaction of said amide-alcohol with thionyl chloride in order to obtain a chlorinated amide; (d) reaction of said chlorinated amide with a phthalimide salt in order to obtain a phthalimide derivative; (e) hydrolysis of the phthalimide group of said phthalimide derivative in order to obtain (1S, 2R)-milnacipran, and (f) salification of (1S, 2R)-milnacipran in a suitable solvent system in the presence of a pharmaceutically acceptable acid.

  本发明涉及一种合成(1S,2R)-米纳西普兰的药物可接受的酸加成盐的方法，包括以下连续步骤：(a)在含有碱性金属的碱基存在下，使苯乙腈和(R)-环氧氯丙烷反应，然后进行碱性处理，接着进行酸性处理以获得内酯；(b)将所述内酯与MNEt2反应，其中M代表碱性金属，或在Lewis酸-胺复合物的存在下与NHEt2反应，以获得酰胺-醇；(c)将所述酰胺-醇与氯化亚砜反应，以获得氯化酰胺；(d)将所述氯化酰胺与邻酞酰亚胺盐反应，以获得邻酞酰亚胺衍生物；(e)水解所述邻酞酰亚胺衍生物的邻酞酰基，以获得(1S,2R)-米纳西普兰；(f)在适当的溶剂体系中，在药学上可接受的酸的存在下，对(1S,2R)-米纳西普兰进行盐化。
• Indole compounds and use thereof
  申请人：Glaxo Group Limited

  公开号：US04252803A1

  公开（公告）日：1981-02-24

  Compounds are disclosed of general formula (I): ##STR1## wherein R.sub.1 and R.sub.2 each independently represents a hydrogen atom, or an aryl, aralkyl, cycloalkyl, fluoroalkyl or alkyl group, which alkyl group is optionally substituted by an alkenyl group or by a group -OR.sub.7 or by ##STR2## where R.sub.7 and R.sub.8 each independently represents a hydrogen atom, an alkyl, aryl or aralkyl group; or R.sub.1 and R.sub.2 together with the nitrogen atom to which they are attached form a saturated monocyclic 5 to 7 membered ring which may contain a further hetero function (viz--O--, --NH or ##STR3## R.sub.3 and R.sub.4 have the same meanings as R.sub.1 and R.sub.2 and may together form an aralkylidene group; R.sub.5 represents a hydrogen atom or an alkyl or aralkyl group; R.sub.6 represents a hydrogen atom or an aryl or C.sub.1 -C.sub.3 alkyl group; Alk represents an C.sub.1 -C.sub.4 alkylene group optionally substituted at one or more of its carbon atoms by one to three C.sub.1 -C.sub.3 alkyl groups; and X represents an oxygen or sulphur atom, and its physiologically acceptable salts, hydrates and bioprecursors. The indoles (I) may be prepared by combinations of reactions to introduce the desired substituents into suitable intermediates either before or after cyclization to form the indole nucleus. The compounds have selective actions on blood vessels and, in particular exhibit antihypertensive properties. They may be formulated in conventional manner as pharmaceutical compositions.

  本发明揭示了一般式（I）的化合物：##STR1## 其中R.sub.1和R.sub.2各自独立地表示氢原子或芳基、芳基烷基、环烷基、氟烷基或烷基，该烷基可被烯基或基团-OR.sub.7或##STR2##所取代，其中R.sub.7和R.sub.8各自独立地表示氢原子、烷基、芳基或芳基烷基；或者R.sub.1和R.sub.2与它们附着的氮原子一起形成饱和的单环5至7成员环，该环可以含有进一步的杂原子（即-O-，-NH或##STR3##R.sub.3和R.sub.4与R.sub.1和R.sub.2具有相同的含义，可以共同形成芳基烷基亚甲基基团；R.sub.5表示氢原子或烷基或芳基烷基；R.sub.6表示氢原子或芳基或C.sub.1-C.sub.3烷基；Alk表示C.sub.1-C.sub.4烷基，其在一个或多个碳原子上可以被一个至三个C.sub.1-C.sub.3烷基取代；X表示氧原子或硫原子，以及其生理上可接受的盐、水合物和生物前体。可通过反应的组合来将所需的取代基引入适当的中间体，然后将其环化形成吲哚核。这些化合物对血管具有选择性作用，并且特别表现出降压特性。它们可以按照常规方法制成制药组合物。