methyl-[(1,2,3,4-tetrahydro-9-yl)acridine]carboxylate | 55618-86-5

• 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: methyl-[(1,2,3,4-tetrahydro-9-yl)acridine]carboxylate
• 英文别名: methyl 1,2,3,4-tetrahydroacridine-9-carboxylate；1,2,3,4-tetrahydro-acridine-9-carboxylic acid methyl ester；1,2,3,4-Tetrahydro-acridin-9-carbonsaeure-methylester
• CAS: 55618-86-5
• 化学式: C₁₅H₁₅NO₂
• mdl: MFCD00435229
• 分子量: 241.29
• InChiKey: UIINMWIYQHIFQH-UHFFFAOYSA-N

物化性质

• 熔点：
  167-168 °C
• 沸点：
  418.3±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  methyl-[(1,2,3,4-tetrahydro-9-yl)acridine]carboxylate 在 potassium tert-butylate 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.5h， 生成 8-(1,2,3,4-tetrahydro-9-acridine-9-yl)oct-7-enenitrile
  参考文献：
  名称：

  Development of Molecular Probes for the Identification of Extra Interaction Sites in the Mid-Gorge and Peripheral Sites of Butyrylcholinesterase (BuChE). Rational Design of Novel, Selective, and Highly Potent BuChE Inhibitors

  摘要：

  Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis of the investigation of the active site gorge topology of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) and by using flexible docking procedures, molecular modeling studies formulated the hypothesis of extra interaction sites in the active gorge of hBuChE, namely, a mid-gorge interaction site and a peripheral interaction site. The design strategy led to novel BuChE inhibitors, balancing potency and selectivity. Among the compounds identified, the heterobivalent ligand 4m, containing an amide nitrogen and a sulfur atom at the 8-membered tether level, is one of the most potent and selective BuChE inhibitors described to date. The novel inhibitors, bearing postulated key features, validated the hypothesis of the presence of extra interaction sites within the hBuChE active site gorge.

  DOI：

  10.1021/jm049510k
• 作为产物：
  描述：

  重氮甲烷 、 1,2,3,4-四氢丫啶-9-羧酸 以 甲醇 为溶剂， 反应 2.0h， 以96%的产率得到methyl-[(1,2,3,4-tetrahydro-9-yl)acridine]carboxylate
  参考文献：
  名称：

  Development of Molecular Probes for the Identification of Extra Interaction Sites in the Mid-Gorge and Peripheral Sites of Butyrylcholinesterase (BuChE). Rational Design of Novel, Selective, and Highly Potent BuChE Inhibitors

  摘要：

  Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis of the investigation of the active site gorge topology of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) and by using flexible docking procedures, molecular modeling studies formulated the hypothesis of extra interaction sites in the active gorge of hBuChE, namely, a mid-gorge interaction site and a peripheral interaction site. The design strategy led to novel BuChE inhibitors, balancing potency and selectivity. Among the compounds identified, the heterobivalent ligand 4m, containing an amide nitrogen and a sulfur atom at the 8-membered tether level, is one of the most potent and selective BuChE inhibitors described to date. The novel inhibitors, bearing postulated key features, validated the hypothesis of the presence of extra interaction sites within the hBuChE active site gorge.

  DOI：

  10.1021/jm049510k

文献信息

• Quinoline-4-methyl esters as human nonpancreatic secretory phospholipase A2 inhibitors
  作者：Yiran Wu、Zheng Chen、Ying Liu、Lanlan Yu、Lu Zhou、Suijia Yang、Luhua Lai

  DOI：10.1016/j.bmc.2011.04.039

  日期：2011.6

  A series of novel fused heterocycle methyl esters were designed and synthesized as human nonpancreatic secretory phospholipase A2 (hnps-PLA2) competitive inhibitors. Among the 22 synthesized compounds, 17 quinoline-4-methyl esters displayed hnps-PLA2 inhibition activity in the in vitro bioassay. The IC50 value for the best compound 3o was 1.5 μM. The structure-inhibition–activity relationships of the

  设计并合成了一系列新颖的稠合杂环甲基酯作为人非胰腺分泌型磷脂酶A 2（hnps-PLA 2）竞争性抑制剂。在22种合成化合物中，有17种喹啉-4-甲酯在体外生物测定中显示出hnps-PLA 2抑制活性。最佳化合物3o的IC 50值为1.5μM。使用分子对接研究了化合物的结构-抑制-活性关系。
• Metal-free C(sp³)–H functionalization (C–C and C–N bond formation) of 1,2,3,4-tetrahydroacridines using deep eutectic solvents as catalyst and reaction medium
  作者：Thangellapally Shirisha、Subir Majhi、Sridhar Balasubramanian、Dhurke Kashinath

  DOI：10.1039/d3ob01752d

  日期：——

  Herein, we report a metal-free and efficient method for the C(sp3)–H functionalization of 1,2,3,4-tetrahydroacridines at the C4-position by the addition of azodicarboxylates (C–N bond) and maleimides (C–C bond) using deep eutectic solvents (DESs) at 80 °C. The C4-functionalized 1,2,3,4-tetrahydroacridines were achieved with high atom efficiency, precise regioselectivity, and yields ranging from 70–96%

  在此，我们报告了一种无金属且有效的方法，通过添加偶氮二羧酸酯（C-N键）和马来酰亚胺，在C4位上对1,2,3,4-四氢吖啶进行C(sp 3 )-H官能化（ C-C 键）在 80 °C 下使用低共熔溶剂 (DES)。 C4 官能化的 1,2,3,4-四氢吖啶具有高原子效率、精确的区域选择性和 70-96% 的产率。所开发方法的实用性已通过克级合成得到证明。还计算了所开发方法的绿色指标，发现这些指标接近理想值。
• Borsche, Justus Liebigs Annalen der Chemie, 1910, vol. 377, p. 119
  作者：Borsche

  DOI：——

  日期：——
• ABRAMOCHKIN EH. S.; KONSHIN M. E.; KADYRMATOVA T. P., XIMIYA EHLEMENTOORGAN. SOEDIN.11, 1V, V, V1 GRUPP PERIODICH. SISTEMY. 161+
  作者：ABRAMOCHKIN EH. S.、 KONSHIN M. E.、 KADYRMATOVA T. P.

  DOI：——

  日期：——
• ABRAMOCHKIN EH. S.; KONSHIN M. E., NAUCH. TR. PERM. FARMATSEVT. IN-T, 1980, HO 14, 17-20
  作者：ABRAMOCHKIN EH. S.、 KONSHIN M. E.

  DOI：——

  日期：——