3-(5-bromo-1H-indole-3-yl)-N-methylsuccinimide | 163886-93-9

• 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
• 英文名称: 3-(5-bromo-1H-indole-3-yl)-N-methylsuccinimide
• 英文别名: 3-(5-bromo-1H-indole-3-yl)-1-methylpyrrolidine-2,5-dione；3-(5-bromo-1H-indol-3-yl)-N-methylsuccinimide；3-(5-bromoindol-3-yl)-N-methylsuccinimide；(5-bromoindol-3-yl)-N-methylsuccinimide；3-(5-bromo-1H-indol-3-yl)-1-methylpyrrolidine-2,5-dione
• CAS: 163886-93-9
• 化学式: C₁₃H₁₁BrN₂O₂
• 分子量: 307.147
• InChiKey: GQURESRVCLILCO-UHFFFAOYSA-N

物化性质

• 沸点：
  532.0±50.0 °C(Predicted)
• 密度：
  1.655±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  53.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(5-bromo-1H-indole-3-yl)-N-methylsuccinimide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以48%的产率得到5-bromo-3-(N-methylpyrrolidin-3-yl)-1H-indole
  参考文献：
  名称：

  A Direct Synthesis of 3-(Pyrrolidin-3-yl)indoles for Use As Conformationally Restricted Analogs of Tryptamines

  摘要：

  本文描述了一种 3-(吡咯烷-3-基)吲哚 4 的高效两步合成法。吲哚与马来酰亚胺在回流乙酸中反应，生成 3-(吲哚-3-基)琥珀酰亚胺 6。反应时间和产量取决于吲哚 5 上的取代基。用 LAH 直接还原琥珀酰亚胺 6，可得到所需的构象受限的色胺衍生物 4。

  DOI：

  10.1055/s-1997-1214
• 作为产物：
  描述：

  3-(5-bromo-1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione 在 bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate 、 (-)-1,2-双[(2R,5R)-2,5-二甲基磷]苯 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 17.5h， 以0%的产率得到
  参考文献：
  名称：

  [EN] INDOLE COMPOUNDS AND METHODS FOR TREATING VISCERAL PAIN
  [FR] COMPOSÉS D'INDOLE ET PROCÉDÉS DE TRAITEMENT DE LA DOULEUR VISCÉRALE

  摘要：

  该发明涉及治疗哺乳动物体内因一氧化氮合酶（NOS）或5-羟色胺受体5HT1D/1B的作用引起的内脏疼痛或疾病的方法，通过向需要治疗的患者施用式(I)的吲哚化合物的治疗有效量，或其药学上可接受的盐或前药。该发明的方法还可以包括额外治疗剂的施用。该发明还涉及式(I)的新化合物、其药物组合物以及解决对映体混合物的方法。

  公开号：

  WO2009062319A1

文献信息

• 5-arylindole derivatives
  申请人：Pfizer Inc.

  公开号：US05994352A1

  公开（公告）日：1999-11-30

  Compounds of the formula ##STR1## wherein A, B, D, E, and F are each independently nitrogen or carbon; R.sub.1 is hydrogen, C.sub.1 to C.sub.6 alkyl, --(CH.sub.2).sub.n R.sub.7, or C.sub.1 to C.sub.3 alkyl-aryl; R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, aryl, C.sub.1 to C.sub.3 alkyl-aryl, halogen, cyano, nitro, --(CH.sub.2).sub.m NR.sub.8 R.sub.9, --(CH.sub.2).sub.m OR.sub.9, --SR.sub.9, --SO.sub.2 NR.sub.8 R.sub.9, --(CH.sub.2).sub.m NR.sub.8 SO.sub.2 R.sub.9, --(CH.sub.2).sub.m NR.sub.8 CO.sub.2 R.sub.9, --(CH.sub.2).sub.m NR.sub.8 COR.sub.9, --(CH.sub.2).sub.m CONR.sub.7 R.sub.9, or --(CH.sub.2).sub.m CO.sub.2 R.sub.9 ; R.sub.2 and R.sub.3, R.sub.3 and R.sub.4, R.sub.4 and R.sub.5, and R.sub.5 and R.sub.6 may be taken together to form a five- to seven-membered alkyl ring, a six-membered ary ring, a five- to seven-membered heteroalkyl ring, having 1 heteroatom of N, O, or S, or a five- to six-membered heteroaryl ring having 1 or 2 heteroatoms of N, O, or S; R.sub.7 is --OR.sub.10, --SR0.sub.10, --SO.sub.2 NR.sub.10 R.sub.11, --NR.sub.10 SO.sub.2 R.sub.11, --NR.sub.10 CO.sub.2 R.sub.11, --NR.sub.10 COR.sub.11, --CONR.sub.10 R.sub.11, or --CO.sub.2 R.sub.10 ; R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are each independently hydrogen, C.sub.1 to C.sub.6 alkyl, or C.sub.1 to C.sub.3 alkyl-aryl; m is 0, 1, or 2; n is 2, 3, or 4; and the above aryl groups and the aryl moieties of the above alkyl-aryl groups are each independently phenyl or substituted phenyl, wherein said substituted phenyl may be substituted with one to three of C.sub.1 to C.sub.4 alkyl, halogen, hydroxy, cyano, carboxamido, nitro, or C.sub.1 to C.sub.4 alkoxy, and the pharmaceutically acceptable salts thereof. These compounds are useful in treating migraine and other disorders and are new. These compounds are useful psychotherapeutics and are potent serotonin (5-HT.sub.1) agonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain, and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotransmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.

  式为##STR1##的化合物，其中A、B、D、E和F分别独立地为氮或碳；R.sub.1为氢、C.sub.1到C.sub.6烷基、--(CH.sub.2).sub.n R.sub.7，或C.sub.1到C.sub.3烷基-芳基；R.sub.2、R.sub.3、R.sub.4、R.sub.5和R.sub.6分别独立地为氢、C.sub.1到C.sub.6烷基、芳基、C.sub.1到C.sub.3烷基-芳基、卤素、氰基、硝基、--(CH.sub.2).sub.m NR.sub.8 R.sub.9、--(CH.sub.2).sub.m OR.sub.9、--SR.sub.9、--SO.sub.2 NR.sub.8 R.sub.9、--(CH.sub.2).sub.m NR.sub.8 SO.sub.2 R.sub.9、--(CH.sub.2).sub.m NR.sub.8 CO.sub.2 R.sub.9、--(CH.sub.2).sub.m NR.sub.8 COR.sub.9、--(CH.sub.2).sub.m CONR.sub.7 R.sub.9，或--(CH.sub.2).sub.m CO.sub.2 R.sub.9；R.sub.2和R.sub.3、R.sub.3和R.sub.4、R.sub.4和R.sub.5，以及R.sub.5和R.sub.6可以结合在一起形成五至七元烷基环、六元芳环、具有1个N、O或S杂原子的五至七元杂烷基环，或具有1个或2个N、O或S杂原子的五至六元杂芳基环；R.sub.7为--OR.sub.10、--SR0.sub.10、--SO.sub.2 NR.sub.10 R.sub.11、--NR.sub.10 SO.sub.2 R.sub.11、--NR.sub.10 CO.sub.2 R.sub.11、--NR.sub.10 COR.sub.11、--CONR.sub.10 R.sub.11，或--CO.sub.2 R.sub.10；R.sub.8、R.sub.9、R.sub.10和R.sub.11分别独立地为氢、C.sub.1到C.sub.6烷基，或C.sub.1到C.sub.3烷基-芳基；m为0、1或2；n为2、3或4；上述芳基和上述烷基-芳基的芳基基团分别独立地为苯基或取代苯基，其中所述取代苯基可以用C.sub.1到C.sub.4烷基、卤素、羟基、氰基、羧酰胺基、硝基，或C.sub.1到C.sub.4烷氧基取代，并且其药学上可接受的盐。这些化合物在治疗偏头痛和其他疾病方面是有用的，并且是新的。这些化合物是有用的精神治疗药物，是有效的5-羟色胺（5-HT.sub.1）激动剂，可用于治疗抑郁症、焦虑症、进食障碍、肥胖症、药物滥用、集群头痛、偏头痛、疼痛，以及与血管疾病相关的慢性阵发性半头痛和头痛等疾病，以及由于5-羟色胺神经传导不足而引起的其他疾病。这些化合物还可用作中枢作用降压药和扩血管药。
• BF3-OEt2 Catalyzed C3-Alkylation of Indole: Synthesis of Indolylsuccinimidesand Their Cytotoxicity Studies
  作者：Iqbal N. Shaikh、Abdul Rahim、Shaikh Faazil、Syed Farooq Adil、Mohamed E. Assal、Mohammad Rafe Hatshan

  DOI：10.3390/molecules26082202

  日期：——

  amongst the series with IC50 value 0.02 µM and 0.8 µM against HT-29 and Hepg2 cell lines, respectively, and compound 3i was most active amongst the series with IC50 value 1.5 µM against A549 cells. Molecular docking study and mechanism of reaction have briefly beendiscussed. This method is better than previous reports in view of yield and substrate scope including electron deficient indoles.

  已经开发了简单有效的由BF 3 -OEt 2促进的吲哚的C 3-烷基化以从市售的吲哚和马来酰亚胺获得3-吲哚基琥珀酰亚胺，在温和的反应条件下具有优异的收率。此外，评估了这些缀合物对HT-29（结肠直肠），Hepg2（肝）和A549（肺）人癌细胞系的抗增殖活性。具有N，N-N-二甲基二吲哚基琥珀酰亚胺的化合物3w是该系列的有效同类物，其针对HT-29和Hepg2细胞系的IC 50值分别为0.02 µM和0.8 µM，而化合物3i在该系列化合物中最活跃。 IC 50对A549细胞的取值为1.5 µM。简要讨论了分子对接的研究和反应机理。考虑到产率和包括电子缺陷的吲哚在内的底物范围，该方法优于以前的报道。
• 5-alkenyl and 5-alkynyl indole compounds
  申请人：Allelix Biopharmaceuticals Inc.

  公开号：US05856510A1

  公开（公告）日：1999-01-05

  Described herein are compounds selective for 5-HT.sub.1D -like receptors, which have the general formula: ##STR1## wherein: R.sup.1 is selected from H, aryl and aryl substituted with 1, 2 or 3 substituents independently selected from loweralkyl, loweralkoxy, loweralkylcarbonyl, loweralkyl-S--, loweralkyl-S(O)--, loweralkyl-SO.sub.2 -, S.dbd.C.dbd.N--, O.dbd.C.dbd.N--, halo, loweralkoxycarbonyl, nitro, amino, loweralkyl-NH--, (loweralkyl).sub.2 --N--, loweralkyl-SO.sub.2 -loweralkyl-; A is a double or triple bond; R.sup.2 is selected from a group of Formula II, III, IV and V: ##STR2## R.sup.3 is selected from H and loweralkyl; R.sup.4 is selected from H and loweralkyl; One of R.sup.5 and R.sup.6 is H and the other is independently selected from H, loweralkoxy, loweralkyl and hydroxy; and R.sup.7 and R.sup.8 are independently selected from H and loweralkyl or R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form an optionally substituted 3- to 6-membered ring; or a salt, solvate or hydrate thereof. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of the 5-HT.sub.1D -like receptor is implicated, such as migraine.

  本文描述了选择性作用于5-HT.sub.1D-类受体的化合物，其具有以下一般式：##STR1##其中：R.sup.1从H、芳基和芳基中选择，所述芳基经1、2或3个取代基独立选择自loweralkyl、loweralkoxy、loweralkylcarbonyl、loweralkyl-S--、loweralkyl-S(O)--、loweralkyl-SO.sub.2-、S.dbd.C.dbd.N--、O.dbd.C.dbd.N--、卤素、loweralkoxycarbonyl、硝基、氨基、loweralkyl-NH--、(loweralkyl).sub.2--N--、loweralkyl-SO.sub.2-loweralkyl-；A为双键或三键；R.sup.2从Formula II、III、IV和V的一组中选择：##STR2##R.sup.3从H和loweralkyl中选择；R.sup.4从H和loweralkyl中选择；R.sup.5和R.sup.6中的一个为H，另一个独立选择自H、loweralkoxy、loweralkyl和羟基；R.sup.7和R.sup.8独立选择自H和loweralkyl，或R.sup.7和R.sup.8与它们连接的氮原子一起形成一个可选择取代的3-至6-成员环；或其盐、溶剂化合物或水合物。还描述了将这些化合物用作药物治疗刺激5-HT.sub.1D-类受体所涉及的适应症，如偏头痛。
• Thiophene-tryptamine derivatives
  申请人：Allelix Biopharmaceuticals Inc.

  公开号：US05770742A1

  公开（公告）日：1998-06-23

  5-Thiophene-substituted tryptamine analogs are provided, which exhibit selectivity towards 5-HT.sub.D1 receptors and consequently show potential in alleviation of the symptoms of migraine. The analogs are represented by the following general chemical formula: ##STR1## in which X represents H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 hydroxyalkyl or halogen, at the 4- or 5-position of the thiophene nucleus; Y represents a direct bond or a C.sub.1 -C.sub.3 alkylene group optionally substituted with hydroxyl: and Z represents amino, mono- or di-N-lower alkyl-substituted amino, or optionally N-lower alkyl-substituted pyrrolidine.

  提供了一种5-噻吩取代的色胺类似物，它们对5-HT.sub.D1受体表现出选择性，并因此显示出缓解偏头痛症状的潜力。这些类似物可以用以下一般化学式表示：##STR1## 其中X代表H、C.sub.1 -C.sub.4 烷基、C.sub.1 -C.sub.4 羟基烷基或卤素，位于噻吩核的4位或5位；Y代表直接键或可选择性地被羟基取代的C.sub.1 -C.sub.3 亚烷基；Z代表氨基、单或双-N-低级烷基取代的氨基，或可选择性地被N-低级烷基取代的吡咯烷。
• 5-alkyl indole compounds
  申请人：Allelix Biopharmaceuticals Inc.

  公开号：US05998462A1

  公开（公告）日：1999-12-07

  Described herein are compounds selective for the 5-HT.sub.1D -like receptor, which have the general formula: ##STR1## wherein: R.sup.1 is linear or branched loweralkyl; R.sup.2 is selected from a group of Formula II, III, IV and V: ##STR2## R.sup.3 is selected from H and loweralkyl; R.sup.4 is selected from H and loweralkyl; One of R.sup.5 and R.sup.6 is H and the other is independently selected from H, loweralkoxy, loweralkyl and hydroxy; and n is 1-3; or a salt, solvate or hydrate thereof. Also described is the use of these compounds as pharmaceuticals to treat indications where stimulation of the 5-HT.sub.1D -like receptor is implicated, such as migraine.

  本文描述了对5-HT.sub.1D-样受体具有选择性的化合物，其具有以下通用公式：其中：R.sup.1是线性或支链低碳烷基；R.sup.2选自公式II、III、IV和V的一组：R.sup.3选自H和低碳烷基；R.sup.4选自H和低碳烷基；R.sup.5和R.sup.6中的一个是H，另一个独立选自H、低碳氧基、低碳烷基和羟基；n为1-3；或其盐、溶剂合物或水合物。还描述了将这些化合物用作药物治疗刺激5-HT.sub.1D-样受体相关的适应症，如偏头痛。