1-[3-(3-hydroxypropyl)-1H-indol-5-yl]-N-methylmethanesulfonamide | 151140-65-7

• 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: 1-[3-(3-hydroxypropyl)-1H-indol-5-yl]-N-methylmethanesulfonamide
• 英文别名: 3-(3-hydroxypropyl)-1H-indol-3-yl-N-methylmethanesulfonamide；C-[3-(3-hydroxypropyl)-1H-indol-5-yl]-N-methyl-methanesulfonamide；3-(3-hydroxypropyl)-N-methyl-1H-indole-5-methanesulfonamide；3-[5-(N-(Methyl)aminosulphonylmethyl)-1H-indol-3-yl]propan-1-ol
• CAS: 151140-65-7
• 化学式: C₁₃H₁₈N₂O₃S
• 分子量: 282.364
• InChiKey: XINMFEAHXJVBRG-UHFFFAOYSA-N

物化性质

• 沸点：
  543.0±60.0 °C(Predicted)
• 密度：
  1.335±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  90.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[3-(3-hydroxypropyl)-1H-indol-5-yl]-N-methylmethanesulfonamide 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 吡啶 、 丙酮 为溶剂， 反应 3.5h， 生成 avitriptan
  参考文献：
  名称：

  An Efficient Fischer Indole Synthesis of Avitriptan, a Potent 5-HT_1D Receptor Agonist

  摘要：

  An efficient synthesis of the antimigraine drug candidate avitriptan (1, BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazine 6 and 5-chlorovaleraldehyde, 20, to give the chloropropylindole 35, which is susceptible to acid-catalyzed degradation under the reaction conditions required for its formation. Sequential coupling of 35 with piperazine, 26, and 4-chloro-5-methoxypyrimidine, 24, gives the title compound in 40-45% overall yield. Significant improvements in the syntheses of the known starting materials, hydrazine 6, 5-chlorovaleraldehyde, 20, and 4-chloro-5-methoxypyrimidine, 24, were also achieved.

  DOI：

  10.1021/jo971368q
• 作为产物：
  描述：

  4-氨基苯基-N-甲基甲烷磺酰胺 在 盐酸 、 sodium hydroxide 、 磷酸 、 tin(ll) chloride 、 sodium nitrite 作用下， 反应 6.0h， 生成 1-[3-(3-hydroxypropyl)-1H-indol-5-yl]-N-methylmethanesulfonamide
  参考文献：
  名称：

  An Efficient Fischer Indole Synthesis of Avitriptan, a Potent 5-HT_1D Receptor Agonist

  摘要：

  An efficient synthesis of the antimigraine drug candidate avitriptan (1, BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazine 6 and 5-chlorovaleraldehyde, 20, to give the chloropropylindole 35, which is susceptible to acid-catalyzed degradation under the reaction conditions required for its formation. Sequential coupling of 35 with piperazine, 26, and 4-chloro-5-methoxypyrimidine, 24, gives the title compound in 40-45% overall yield. Significant improvements in the syntheses of the known starting materials, hydrazine 6, 5-chlorovaleraldehyde, 20, and 4-chloro-5-methoxypyrimidine, 24, were also achieved.

  DOI：

  10.1021/jo971368q

文献信息

• Indolylalkyl derivatives of pyrimidinylpiperazine for treating vascular
  申请人：Bristol-Myers Squibb Company

  公开号：US05300506A1

  公开（公告）日：1994-04-05

  A series of novel indol-3-ylalkyl derivatives of alkoxypyrimidinylpiperazines are disclosed as Formula I. ##STR1## These compounds are intended to be useful agents for alleviation of vascular headache on the basis of their potent affinity and agonist activity at 5-HT1D binding sites.

  一系列新颖的吲哚-3-基烷基衍生物的烷氧基嘧啶基哌嗪被披露为公式I。这些化合物旨在通过它们在5-HT1D结合位点的强亲和力和激动剂活性来缓解血管性头痛。
• INDOLYLALKYL DERIVATIVES OF PYRIMIDINYLPIPERAZINE AND METABOLITES THEREOF FOR TREATMENT OF ANXIETY, DEPRESSION, AND SEXUAL DYSFUNCTION
  申请人：KRAMER Stephen J.

  公开号：US20090281114A1

  公开（公告）日：2009-11-12

  The present invention relates to a method for alleviation, prevention, and treatment of anxiety, depression, and sexual dysfunction by administering certain indolylalkyl derivatives of pyrimidinylpiperazine or metabolites thereof. A preferred embodiment is of the following formula:

  本发明涉及通过给予某些吡咯啉基吡咯嗪的衍生物或其代谢物来缓解、预防和治疗焦虑、抑郁和性功能障碍的方法。一种首选实施例的化学式如下：
• Antimigraine 4-pyrimidinyl and pyridinyl derivatives of
  申请人：Bristol-Myers Squibb Company

  公开号：US05434154A1

  公开（公告）日：1995-07-18

  A series of novel alkoxypyridin-4-yl and alkoxypyrimidin-4-yl derivatives of indol-3-ylalkylpiperazines of Formula I are intended to be useful agents ##STR1## for alleviation of vascular headache on the basis of their potent affinity and agonist activity at 5-HT1D binding sites.

  一系列新颖的Formula I的吲哚-3-基烷基哌嗪的烷氧基吡啶-4-基和烷氧基吡啶-4-基衍生物旨在成为有用的药剂，用于缓解血管性头痛，基于它们在5-HT1D结合位点的强亲和力和激动剂活性。
• 3-[3-(Piperidin-1-yl)propyl]indoles as Highly Selective h5-HT_1D Receptor Agonists
  作者：Michael G. N. Russell、Victor G. Matassa、Roy R. Pengilley、Monique B. van Niel、Bindi Sohal、Alan P. Watt、Laure Hitzel、Margaret S. Beer、Josephine A. Stanton、Howard B. Broughton、José L. Castro

  DOI：10.1021/jm9910021

  日期：1999.12.2

  5-HT(1D/1B) receptor agonists are now entering the marketplace as treatments for migraine. This paper describes the development of selective h5-HT(1D) receptor agonists as potential antimigraine agents which may produce fewer side effects. A series of 3-[3-(piperidin-1-yl)propyl]indoles has been synthesized which has led to the identification of 80 (L-772,405), a high-affinity h5-HT(1D) receptor full agonist

  几种5-HT（1D / 1B）受体激动剂目前正作为偏头痛的治疗方法进入市场。本文介绍了选择性的h5-HT（1D）受体激动剂作为潜在的偏头痛药物的发展，它可能产生较少的副作用。合成了一系列3- [3-（哌啶-1-基）丙基]吲哚，该化合物导致鉴定出80（L-772,405），这是一种具有170的高亲和力h5-HT（1D）受体全激动剂对h5-HT（1D）受体的选择性是h5-HT（1B）受体的两倍。L-772,405在一系列其他5-羟色胺和非5-羟色胺受体上也表现出非常好的选择性，并且在大鼠皮下给药后具有出色的生物利用度。因此，它构成了描述偏头痛中h5-HT（1D）受体作用的有价值的工具。
• INDOL DERIVATIVES USEFUL FOR THE TREATMENT OF MIGRAINE, COMPOSITION AND UTILIZATION
  申请人：VITA-INVEST, S.A.

  公开号：EP0714896A1

  公开（公告）日：1996-06-05

  Indole derivatives having the Formula (I) wherein R₁ is H, alkyl or acyl group; R₂ is H, halogen or alkyl, hydroxy, alkoxy; ciano, carboxamide, carboxyl, alkoxicarbonyl, phenyl, phenyloxy or a group -(CH₂)n-R₆, (n=1-3), and R₆ is a group ciano, nitro, phenyl, carboxyl, -CO₂R₇; -CONR₇R₈; -SO₂NR₇R₈; -COR₇; -SO₂R₇, R₇ and R₈ being H or alkyl; R₇ and R₈, together with N, can form a cycle of 4-7 links; R₃, R₄ and R₅ are H, halogen or a group alkyl, phenyl, substituted phenyl, hydroxy, alcoxy, phenyloxy or benziloxy; NR₁₁R₁₂ is H or a group ciano, nitro, carboxyl, alcoxycarbonyl, carboxamido or a group R₃; A is an alkyliden group -(CH₂)-m, (m = 1-5), or alkenyl group; B is a piperazinoring (a), aminopyrrolidinoring (b); pyrrolidinamino ring (c); piperidinoring (d) or ethylendiamino -NR₉-CH₂-CH₂-NR₁₀-, R₉ and R₁₀ being H or an alkyl group. The compounds are useful for the treatment of migraine.

  吲哚衍生物具有以下式（I）其中R₁为H、烷基或酰基；R₂为H、卤素或烷基、羟基、烷氧基；氰基、羧酰胺基、羧基、烷氧基羰基、苯基、苯氧基或一个基团-(CH₂)n-R₆，（n=1-3），且R₆为一个基团氰基、硝基、苯基、羧基、-CO₂R₇；-CONR₇R₈；-SO₂NR₇R₈；-COR₇；-SO₂R₇，R₇和R₈为H或烷基；R₇和R₈，与N一起，可形成一个4-7个连接的环；R₃、R₄和R₅为H、卤素或一个烷基、苯基、取代苯基、羟基、烷氧基、苯氧基或苄氧基基团；NR₁₁R₁₂为H或一个基团氰基、硝基、羧基、烷氧羰基、羧酰胺基或一个基团R₃；A为一个烷基亚甲基基团-(CH₂)-m，（m=1-5），或烯基基团；B为哌嗪环（a）、氨基吡咯啉环（b）；吡咯啉氨基环（c）；哌啶环（d）或乙二胺-NR₉-CH₂-CH₂-NR₁₀-，R₉和R₁₀为H或一个烷基基团。这些化合物可用于治疗偏头痛。