2,3-dihydro-1-<(1,2,3,6-tetrahydro-1-methyl-4-pyridyl)carbonyl>-1H-indole | 141474-75-1

• 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: 2,3-dihydro-1-<(1,2,3,6-tetrahydro-1-methyl-4-pyridyl)carbonyl>-1H-indole
• 英文别名: 2,3-dihydroindol-1-yl-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)methanone
• CAS: 141474-75-1
• 化学式: C₁₅H₁₈N₂O
• 分子量: 242.321
• InChiKey: CJPWMECBMXFGOO-UHFFFAOYSA-N

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：
  0.4
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-1-<(1,2,3,6-tetrahydro-1-methyl-4-pyridyl)carbonyl>-1H-indole 在 N,N-二异丙基乙胺 作用下， 以 甲苯 为溶剂， 反应 29.0h， 生成 cis-4,5,7a,8,9,10,11,11a-octahydro-7-oxo-7H-indolo<1,7-bc><2,6>naphthyridine-10-carbamic acid ethyl ester
  参考文献：
  名称：

  (+)-cis-4,5,7a,8,9,10,11,11a-Octahydro-7H-10-methylindolo[1,7-bc][2,6]- naphthyridine: A 5-HT2C/2B Receptor Antagonist with Low 5-HT2A Receptor Affinity

  摘要：

  The indolonaphthyridine 8 is described as a selective 5-HT2C/2B vs 5-HT2A receptor antagonist. The compound was synthesized in seven steps starting from indoline and isonicotinic acid chloride. The key step is a photocyclization of the indolinyl tetrahydropyridinocarbamic acid ethyl ester 4 to the cis-octahydroindolo[1,7-bc][2,6]naphthyrdinecarbamic acid ethyl ester 5. The synthesis was accomplished by reduction with aluminum hydride and racemic resolution. The indolonaphthyridine 8 exerted the binding profile of a selective 5-HT2C receptor ligand (pK(D) 7.8) and behaved as an antagonist on the 5-HT-induced accumulation of inositol phosphates in pig choroid plexus cells (pK(B) 7.13). Compound 8 dose-dependently inhibited the ACTH response to MK-212 in rats and the MK-212-induced hypophagic effect with an ID50 value of 0.3 mg/kg sc. Compound 8 acted as a 5-HT2B receptor antagonist at the rat stomach fundus with a pK(B) value of 7.34.

  DOI：

  10.1021/jm00001a007
• 作为产物：
  描述：

  4-<(2,3-dihydro-1H-indol-1-yl)carbonyl>-1-methylpyridinium iodide 在 sodium hydroxide 、 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以67%的产率得到2,3-dihydro-1-<(1,2,3,6-tetrahydro-1-methyl-4-pyridyl)carbonyl>-1H-indole
  参考文献：
  名称：

  (+)-cis-4,5,7a,8,9,10,11,11a-Octahydro-7H-10-methylindolo[1,7-bc][2,6]- naphthyridine: A 5-HT2C/2B Receptor Antagonist with Low 5-HT2A Receptor Affinity

  摘要：

  The indolonaphthyridine 8 is described as a selective 5-HT2C/2B vs 5-HT2A receptor antagonist. The compound was synthesized in seven steps starting from indoline and isonicotinic acid chloride. The key step is a photocyclization of the indolinyl tetrahydropyridinocarbamic acid ethyl ester 4 to the cis-octahydroindolo[1,7-bc][2,6]naphthyrdinecarbamic acid ethyl ester 5. The synthesis was accomplished by reduction with aluminum hydride and racemic resolution. The indolonaphthyridine 8 exerted the binding profile of a selective 5-HT2C receptor ligand (pK(D) 7.8) and behaved as an antagonist on the 5-HT-induced accumulation of inositol phosphates in pig choroid plexus cells (pK(B) 7.13). Compound 8 dose-dependently inhibited the ACTH response to MK-212 in rats and the MK-212-induced hypophagic effect with an ID50 value of 0.3 mg/kg sc. Compound 8 acted as a 5-HT2B receptor antagonist at the rat stomach fundus with a pK(B) value of 7.34.

  DOI：

  10.1021/jm00001a007

文献信息

• Indolonaphthyridine
  申请人：SANDOZ LTD.

  公开号：EP0473550A1

  公开（公告）日：1992-03-04

  Indolonaphthyridine der Formel I, worin R₁, R₂, R₃, R₄, R₅, X und Y wie in der Beschreibung definiert sind, ihre Herstellung und Anwendung als Therapeutika.

  式 I 的吲哚萘啶、 其中 R₁、R₂、R₃、R₄、R₅、X 和 Y 如说明中定义，其制备和用作治疗。
• (+)-cis-4,5,7a,8,9,10,11,11a-Octahydro-7H-10-methylindolo[1,7-bc][2,6]- naphthyridine: A 5-HT2C/2B Receptor Antagonist with Low 5-HT2A Receptor Affinity
  作者：Joachim Nozulak、Hans O. Kalkman、Philipp Floerscheim、Daniel Hoyer、Philipp Schoeffter、Hans R. Buerki

  DOI：10.1021/jm00001a007

  日期：1995.1

  The indolonaphthyridine 8 is described as a selective 5-HT2C/2B vs 5-HT2A receptor antagonist. The compound was synthesized in seven steps starting from indoline and isonicotinic acid chloride. The key step is a photocyclization of the indolinyl tetrahydropyridinocarbamic acid ethyl ester 4 to the cis-octahydroindolo[1,7-bc][2,6]naphthyrdinecarbamic acid ethyl ester 5. The synthesis was accomplished by reduction with aluminum hydride and racemic resolution. The indolonaphthyridine 8 exerted the binding profile of a selective 5-HT2C receptor ligand (pK(D) 7.8) and behaved as an antagonist on the 5-HT-induced accumulation of inositol phosphates in pig choroid plexus cells (pK(B) 7.13). Compound 8 dose-dependently inhibited the ACTH response to MK-212 in rats and the MK-212-induced hypophagic effect with an ID50 value of 0.3 mg/kg sc. Compound 8 acted as a 5-HT2B receptor antagonist at the rat stomach fundus with a pK(B) value of 7.34.