4-(3,4-二氢-2(1h)-异喹啉)环己酮 | 166398-23-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 4-(3,4-二氢-2(1h)-异喹啉)环己酮
• 中文别名: 4-(3,4-二氢-2(1H)-异喹啉基)环己酮
• 英文名称: 4-[2-(1,2,3,4-tetrahydroisoquinolinyl)]cyclohexanone
• 英文别名: 4-(Tetrahydroisoquinolin-2yl)cyclohexanone；4-(3,4-dihydroisoquinolin-2(1H)-yl)cyclohexanone；4-(3,4-dihydro-1H-isoquinolin-2-yl)cyclohexan-1-one
• CAS: 166398-23-8
• 化学式: C₁₅H₁₉NO
• 分子量: 229.322
• InChiKey: BYRHPLCFXPSWTK-UHFFFAOYSA-N

物化性质

• 沸点：
  365.4±42.0 °C(Predicted)
• 密度：
  1.124

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 5'-甲烷磺酰氨基-2'-羟基苯乙酮 、 4-(3,4-二氢-2(1h)-异喹啉)环己酮 以 甲醇 为溶剂， 生成 N-[4'-(3,4-dihydro-2(1H)-isoquinolinyl)-3,4-dihydro-4-hydroxyspiro[2H-1-benzopyran-2,1 '-cyclohexan]-6-yl]methanesulfonamide
  参考文献：
  名称：

  Spirocycles

  摘要：

  通式为：##STR1## 或其药用可接受的盐、水合物或晶体形式的对映体、顺反异构体或其混合物是三类抗心律失常药物。

  公开号：

  US05403846A1
• 作为产物：
  描述：

  8-(Tetrahydroisoquinolin-2-yl)-1,4-dioxaspiro[4,5]decane 在 盐酸 作用下， 以 丙酮 为溶剂， 生成 4-(3,4-二氢-2(1h)-异喹啉)环己酮
  参考文献：
  名称：

  On the Bioactive Conformation of NAN-190 (1) and MP3022 (2), 5-HT_1A Receptor Antagonists

  摘要：

  Structural modifications of 1, a postsynaptic 5-HT1A receptor antagonist, provided its flexible (8, 12) and rigid (7, 9, 11, 13) analogues; Compounds 7, 8, 9, and 11 showed high 5-HT1A receptor affinity (K-i = 4-72 nM). They acted as 6-HT1A postsynaptic receptor antagonists, since, like 1, they inhibited the behavioral syndrome, i.e., flat body posture (FBP) and forepaw treading (FT), in reserpine-pretreated rats as well as the lower lip retraction (LLR) in rats, both induced by 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), a 5-HT1A receptor agonist. Compound 12, which demonstrated high 6-HT1A receptor affinity (K-i = 50 nM), revealed properties of a partial 5-HT1A receptor agonist: it induced LLR and, at the same time, inhibited FT in rats. Compound 13 (K-i = 1600 nM) was not tested in a behavioral study. Restriction of the conformational freedom in 2, a full 5-HT1A receptor antagonist, yielded compound 14 with high 5-HT1A receptor affinity (K-i = 47 nM) and partial agonist properties at postsynaptic 5-HT1A receptors in the above tests in vivo; i.e., it induced LLR and inhibited FBP and FT in rats. New constrained analogues of 1 and 2 (compounds 7 and 14, respectively) were also synthesized to recognize a bioactive conformation of those 5-HT1A receptor antagonists. On the basis of in vitro and in vivo investigations, binding and functional properties of compound 7 were found to reflect those of 1 at 5-HT1A receptors. On the other hand, compound 14, a rigid analogue of 2, showed a different activity in vivo in comparison with the parent compound. PM3 and MM calculations revealed the existence of three! low-energy conformers of 7 and six of 14, all of them belonging to the extended family of conformations. The optimized structures of both analogues had a different angle between aromatic planes of terminal fragments; moreover, the heteroaromatic system of those molecules occupied various space regions. Our present study provides support to the hypothesis that the bioactive conformation of 1, responsible for its postsynaptic 5-HT1A receptor antagonism, is an extended linear structure represented by 7.

  DOI：

  10.1021/jm991045h

文献信息

• US5403846A
  申请人：——

  公开号：US5403846A

  公开（公告）日：1995-04-04
• [EN] NOVEL SPIROCYCLES<br/>[FR] NOUVEAUX SPIROCYCLES
  申请人：MERCK & CO., INC.

  公开号：WO1995014469A1

  公开（公告）日：1995-06-01

  (EN) Compounds of general structural formula (I) or a pharmaceutically acceptable salt, hydrate or crystal form enantiomer, diastereomer or mixtures thereof are Class III antiarrhythmic agents.(FR) L'invention concerne des composés présentant la formule générale suivante (I). Ces composés ou un sel pharmaceutiquement acceptable, un hydrate, une forme cristalline, un énantiomère, un diastéréomère ou un mélange de ces derniers sont des agents antiarythmiques de classe III.
• On the Bioactive Conformation of NAN-190 (1) and MP3022 (2), 5-HT_1A Receptor Antagonists
  作者：Maria H. Paluchowska、Maria J. Mokrosz、Andrzej Bojarski、Anna Wesołowska、Jolanta Borycz、Sijka Charakchieva-Minol、Ewa Chojnacka-Wójcik

  DOI：10.1021/jm991045h

  日期：1999.12.2

  Structural modifications of 1, a postsynaptic 5-HT1A receptor antagonist, provided its flexible (8, 12) and rigid (7, 9, 11, 13) analogues; Compounds 7, 8, 9, and 11 showed high 5-HT1A receptor affinity (K-i = 4-72 nM). They acted as 6-HT1A postsynaptic receptor antagonists, since, like 1, they inhibited the behavioral syndrome, i.e., flat body posture (FBP) and forepaw treading (FT), in reserpine-pretreated rats as well as the lower lip retraction (LLR) in rats, both induced by 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), a 5-HT1A receptor agonist. Compound 12, which demonstrated high 6-HT1A receptor affinity (K-i = 50 nM), revealed properties of a partial 5-HT1A receptor agonist: it induced LLR and, at the same time, inhibited FT in rats. Compound 13 (K-i = 1600 nM) was not tested in a behavioral study. Restriction of the conformational freedom in 2, a full 5-HT1A receptor antagonist, yielded compound 14 with high 5-HT1A receptor affinity (K-i = 47 nM) and partial agonist properties at postsynaptic 5-HT1A receptors in the above tests in vivo; i.e., it induced LLR and inhibited FBP and FT in rats. New constrained analogues of 1 and 2 (compounds 7 and 14, respectively) were also synthesized to recognize a bioactive conformation of those 5-HT1A receptor antagonists. On the basis of in vitro and in vivo investigations, binding and functional properties of compound 7 were found to reflect those of 1 at 5-HT1A receptors. On the other hand, compound 14, a rigid analogue of 2, showed a different activity in vivo in comparison with the parent compound. PM3 and MM calculations revealed the existence of three! low-energy conformers of 7 and six of 14, all of them belonging to the extended family of conformations. The optimized structures of both analogues had a different angle between aromatic planes of terminal fragments; moreover, the heteroaromatic system of those molecules occupied various space regions. Our present study provides support to the hypothesis that the bioactive conformation of 1, responsible for its postsynaptic 5-HT1A receptor antagonism, is an extended linear structure represented by 7.
• Spirocycles
  申请人：Merck & Co., Inc.

  公开号：US05403846A1

  公开（公告）日：1995-04-04

  Compounds of the general formula: ##STR1## or a pharmaceutically acceptable salt, hydrate or crystal form enantiomer, diastereomer or mixtures thereof are Class III antiarrhythmic agents.

  通式为：##STR1## 或其药用可接受的盐、水合物或晶体形式的对映体、顺反异构体或其混合物是三类抗心律失常药物。