1-methyl-N-(3-pyridyl)-5,6,7,8-tetrahydro-1H-pyrrolo<2,3-g>quinoline-5-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-methyl-N-(3-pyridyl)-5,6,7,8-tetrahydro-1H-pyrrolo<2,3-g>quinoline-5-carboxamide
• 英文别名: 1-methyl-N-pyridin-3-yl-7,8-dihydro-6H-pyrrolo[2,3-g]quinoline-5-carboxamide
• 化学式: C₁₈H₁₈N₄O
• 分子量: 306.367
• InChiKey: ITVMJNOYTVOMMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  6-氨基喹啉 在 吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 nickel dichloride 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 128.33h， 生成 1-methyl-N-(3-pyridyl)-5,6,7,8-tetrahydro-1H-pyrrolo<2,3-g>quinoline-5-carboxamide
  参考文献：
  名称：

  5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: A Novel 5-HT2C/5-HT2B Receptor Antagonist with Improved Affinity, Selectivity, and Oral Activity

  摘要：

  The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pK(I) 8.0) and 5-HT2B receptors (pA(2) 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pK(I) <6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pK(B) 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.

  DOI：

  10.1021/jm00014a004

文献信息

• CONDENSED INDOLE DERIVATIVES AS 5HT 2C? AND 5HT 2B? ANTAGONISTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0656003A1

  公开（公告）日：1995-06-07
• [EN] CONDENSED INDOLE DERIVATIVES AS 5HT2C AND 5HT2B ANTAGONISTS<br/>[FR] DERIVES D'INDOLE CONDENSES UTILISES COMME ANTAGONISTES DES RECEPTEURS 5HT2C et 5HT2B
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1994004533A1

  公开（公告）日：1994-03-03

  (EN) Compounds of formula (I) or a salt thereof wherein: P represents a quinoline or isoquinoline residue, or a 5- or 6-membered aromatic heterocyclic ring containing up to three heteroatoms selected from nitrogen, oxygen or sulphur; R1 is hydrogen or C1-6 alkyl; R2, R3, R10 and R11 are independently hydrogen or C1-6 alkyl, or R10 and R11 together form a bond, or R2 and R10 or R3 and R11 together form a C2-6 alkylene chain; R4 is hydrogen, C1-6 alkyl, halogen, NR8R9 or OR12, where R8, R9 and R12 are independently hydrogen or C1-6 alkyl; R5 is hydrogen or C1-6 alkyl; R7 is hydrogen, C1-6 alkyl, OR12 or halogen, where R12 is hydrogen or C1-6 alkyl; n is 2 or 3; and the groups R13 and R14 are independently hydrogen or C1-6 alkyl, are 5HT2C/5HT2B receptor antagonists and are of potential use in the treatment of CNS disorders such as anxiety.(FR) Composés de formule (I) ou leur sel, formule dans laquelle P représente un résidu quinoléine ou isoquinoléine, ou bien un composé hétérocyclique aromatique pentagonal ou hexagonal renfermant jusqu'à 3 hétéroatomes choisis parmi azote, oxygène ou soufre; R1 est hydrogène ou alkyle C1-6; R2, R3, R10 et R11 sont indépendamment hydrogène ou alkyle C1-6, ou bien R10 et R11 forment ensemble une liaison, ou encore R2 et R10 ou R3 et R11 forment ensemble une chaîne alkylène C2-6; R4 est hydrogène, alkyle C1-6, halogène, NR8R9 ou OR12, où R8, R9 et R12 sont indépendamment hydrogène ou alkyle C1-6; R5 est hydrogène ou alkyle C1-6; R7 est hydrogène, alkyle C1-6, OR12 ou bien halogène, où R12 est hydrogène ou alkyle C1-6; n vaut 2 ou 3; et les groupes R13 et R14 sont indépendamment hydrogène ou alkyle C1-6. Ces composés sont des antagonistes des récepteurs 5HT2C/5HT2B et sont d'une utilisation potentielle dans le traitement des troubles du système nerveux central, tels que l'anxiété.
• 5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: A Novel 5-HT2C/5-HT2B Receptor Antagonist with Improved Affinity, Selectivity, and Oral Activity
  作者：Ian T. Forbes、Peter Ham、Deborah H. Booth、Roger T. Martin、Mervyn Thompson、Gordon S. Baxter、Thomas P. Blackburn、Alison Glen、Guy A. Kennett、Martyn D. Wood

  DOI：10.1021/jm00014a004

  日期：1995.7

  The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pK(I) 8.0) and 5-HT2B receptors (pA(2) 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pK(I) <6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pK(B) 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.