哌啶-1-基[(3S)-1,2,3,4-四氢-3-异喹啉基]酮 | 256373-09-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 哌啶-1-基[(3S)-1,2,3,4-四氢-3-异喹啉基]酮
• 英文名称: Piperidin-1-yl [(3S)-1,2,3,4-tetrahydro-3-isoquinolyl] ketone
• 英文别名: (3S)-3-(Piperidin-1-ylcarbonyl)-1,2,3,4-tetrahydroisoquinoline；piperidin-1-yl-[(3S)-1,2,3,4-tetrahydroisoquinolin-3-yl]methanone
• CAS: 256373-09-8
• 化学式: C₁₅H₂₀N₂O
• mdl: MFCD17170941
• 分子量: 244.337
• InChiKey: ZCYXCLHBGPYIOE-AWEZNQCLSA-N

物化性质

• 沸点：
  438.2±45.0 °C(Predicted)
• 密度：
  1.125±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：
  0.533
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  哌啶-1-基[(3S)-1,2,3,4-四氢-3-异喹啉基]酮 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 84.0h， 生成 (S)-7-(4-([1,1'-biphenyl]-2-yl)piperazin-1-yl)-1-(3-(piperidine-1-carbonyl)-1,2,3,4-tetrahydroisoquinolin-2-yl)heptan-1-one
  参考文献：
  名称：

  Towards novel 5-HT7 versus 5-HT1A receptor ligands among LCAPs with cyclic amino acid amide fragments: Design, synthesis, and antidepressant properties. Part II

  摘要：

  A 26-membered library of novel long-chain arylpiperazines, which contained primary and tertiary amides of cyclic amino acids (proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxamide) in the terminal fragment was synthesized and biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors. Docking studies confirmed advantages of Tic-amide over Pro-amide fragment for interaction with 5-HT7 receptors. Selected compounds 32 and 28, which behaved as 5-HT(7)Rs antagonist and 5-HT1A partial agonist, respectively, produced antidepressant-like effects in the forced swim test in mice after acute treatment in doses of 10 mg/kg (32) and 1.25 mg/kg (28). Compound 32 reduced immobility in a manner similar to the selective 5-HT7 antagonist SB-269970. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.041
• 作为产物：
  描述：

  N-叔丁氧羰基-(S)-1,2,3,4-四氢异喹啉-3-羧酸 在 三乙基硅烷 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 copper dichloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 哌啶-1-基[(3S)-1,2,3,4-四氢-3-异喹啉基]酮
  参考文献：
  名称：

  构象约束的手性锂酰胺基对映体对4-叔丁基环己酮的对映选择性去质子

  摘要：

  已经制备了基于四氢异喹啉基序的构象刚性的手性锂酰胺，其在C1和C3处带有一系列取代基。在4-叔丁基环己酮的不对称去质子反应中测试了这些碱。尽管1-取代的四氢异喹啉具有较低的对映选择性，但发现在HMPA存在下，在C3处含有氮杂环的手性碱可诱导较高的对映选择性（81％ee）。

  DOI：

  10.1039/a905947d

文献信息

• Enantioselective deprotonation of 4-tert-butylcyclohexanone by conformationally constrained chiral lithium amide bases
  作者：Varinder K. Aggarwal、Paul S. Humphries、Ashley Fenwick

  DOI：10.1039/a905947d

  日期：——

  Conformationally rigid chiral lithium amides based on a tetrahydroisoquinoline motif have been prepared bearing a range of substituents at C1 and C3. These bases were tested in the asymmetric deprotonation reaction of 4-tert-butylcyclohexanone. Although the 1-substituted tetrahydroisoquinolines gave low enantioselectivity, the chiral bases containing a nitrogen heterocycle at C3 were found to induce

  已经制备了基于四氢异喹啉基序的构象刚性的手性锂酰胺，其在C1和C3处带有一系列取代基。在4-叔丁基环己酮的不对称去质子反应中测试了这些碱。尽管1-取代的四氢异喹啉具有较低的对映选择性，但发现在HMPA存在下，在C3处含有氮杂环的手性碱可诱导较高的对映选择性（81％ee）。
• 3-Amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
  申请人：Ashton T Wallace

  公开号：US20060074087A1

  公开（公告）日：2006-04-06

  The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及3-氨基-4-苯基丁酸衍生物，它们是二肽基肽酶-IV酶（“DP-IV抑制剂”）的抑制剂，可用于治疗或预防二肽基肽酶-IV酶涉及的疾病，如糖尿病，特别是2型糖尿病。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗二肽基肽酶-IV酶涉及的这些疾病中使用这些化合物和组合物。
• 3-amino-4-phenylbutanoic acid derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
  申请人：Merck & Co., Inc.

  公开号：US07388019B2

  公开（公告）日：2008-06-17

  The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及3-氨基-4-苯基丁酸衍生物，其是二肽基肽酶IV酶（“DP-IV抑制剂”）的抑制剂，对于涉及二肽基肽酶IV酶的疾病，如糖尿病，尤其是2型糖尿病的治疗或预防有用。本发明还涉及包含这些化合物的制药组合物以及在涉及二肽基肽酶IV酶的这些疾病的预防或治疗中使用这些化合物和组合物。
• US7388019B2
  申请人：——

  公开号：US7388019B2

  公开（公告）日：2008-06-17
• Towards novel 5-HT7 versus 5-HT1A receptor ligands among LCAPs with cyclic amino acid amide fragments: Design, synthesis, and antidepressant properties. Part II
  作者：Vittorio Canale、Rafał Kurczab、Anna Partyka、Grzegorz Satała、Jagna Witek、Magdalena Jastrzębska-Więsek、Maciej Pawłowski、Andrzej J. Bojarski、Anna Wesołowska、Paweł Zajdel

  DOI：10.1016/j.ejmech.2014.12.041

  日期：2015.3

  A 26-membered library of novel long-chain arylpiperazines, which contained primary and tertiary amides of cyclic amino acids (proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxamide) in the terminal fragment was synthesized and biologically evaluated for binding affinity for 5-HT7 and 5-HT1A receptors. Docking studies confirmed advantages of Tic-amide over Pro-amide fragment for interaction with 5-HT7 receptors. Selected compounds 32 and 28, which behaved as 5-HT(7)Rs antagonist and 5-HT1A partial agonist, respectively, produced antidepressant-like effects in the forced swim test in mice after acute treatment in doses of 10 mg/kg (32) and 1.25 mg/kg (28). Compound 32 reduced immobility in a manner similar to the selective 5-HT7 antagonist SB-269970. (C) 2014 Elsevier Masson SAS. All rights reserved.