2-benzyl-7-methoxy-1,2,3,4-tetrahydroisoquinoline | 404848-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2-benzyl-7-methoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-benzyl-7-methoxy-3,4-dihydro-1H-isoquinoline
• CAS: 404848-24-4
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: BJFUCBWZWBOECG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-benzyl-7-methoxy-1,2,3,4-tetrahydroisoquinoline 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 (l)-2-benzyl-7-hydroxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists

  摘要：

  SCH 58261 is a reported adenosine A(2A) receptor antagonist which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A(1) receptor and does not demonstrate oral activity. Quinoline analogs have improved upon the selectivity and pharmacokinetics of SCH 58261, but were difficult to handle due to poor aqueous solubility. We report the design and synthesis of fused heterocyclic analogs of SCH 58261 with aqueous solubility as well as improved A(2A) receptor binding selectivity and pharmacokinetic properties. In particular, the tetrahydronaphthyridine 4s has excellent A(2A) receptor in vitro binding affinity and selectivity, is active orally in a rat in vivo model of Parkinson's Disease, and has aqueous solubility of 100 mu M at physiological pH. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.069
• 作为产物：
  描述：

  1,2,3,4-四氢-7-甲氧基异喹啉盐酸盐 、 溴甲苯 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 2-benzyl-7-methoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists

  摘要：

  SCH 58261 is a reported adenosine A(2A) receptor antagonist which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A(1) receptor and does not demonstrate oral activity. Quinoline analogs have improved upon the selectivity and pharmacokinetics of SCH 58261, but were difficult to handle due to poor aqueous solubility. We report the design and synthesis of fused heterocyclic analogs of SCH 58261 with aqueous solubility as well as improved A(2A) receptor binding selectivity and pharmacokinetic properties. In particular, the tetrahydronaphthyridine 4s has excellent A(2A) receptor in vitro binding affinity and selectivity, is active orally in a rat in vivo model of Parkinson's Disease, and has aqueous solubility of 100 mu M at physiological pH. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.069

文献信息

• 2-Substituted-1,2,3,4-tetrahydroisoquinolines and chiral 3-carboxyl analogues from N-benzotriazolylmethyl-N-phenethylamines
  作者：Alan R Katritzky、Hai-Ying He、Rong Jiang、Qiuhe Long

  DOI：10.1016/s0957-4166(01)00418-9

  日期：2001.9

  N-Benzotriazolylmethyl-N-phenethylamines 5a-5c and 11a-11c cyclize in the presence of aluminum chloride to produce 1,2.3,4-tetrahydroisoquinolines 6a-6c and 12a-12c (70-89%) via electrophilic attack of a transient iminium cation X on the tethered phenyl ring. The Bt group in 2-benzotriazolylmethyl-1,2,3,4-tetrahydroisoquinolines 6a-6b was replaced (i) with hydrogen by sodium borohydride to afford N-methyl-1,2,3,4-tetrahydroisoquinolines 7a-7b or (ii) by nucleophiles, such as Grignard reagents, a silyl enol ether or triethyl phosphite, to furnish novel N-substituted-1,2,3,4-tetrahydroisoquinolines 13a-13c, 14 or 15, respectively. Optically active 3-substituted-1,2,3,4-tetrahydroisoquinolines 12a-12c were similarly prepared in high yields without racemization. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists
  作者：Unmesh Shah、Claire M. Lankin、Craig D. Boyle、Samuel Chackalamannil、William J. Greenlee、Bernard R. Neustadt、Mary E. Cohen-Williams、Guy A. Higgins、Kwokei Ng、Geoffrey B. Varty、Hongtao Zhang、Jean E. Lachowicz

  DOI：10.1016/j.bmcl.2008.05.069

  日期：2008.7

  SCH 58261 is a reported adenosine A(2A) receptor antagonist which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A(1) receptor and does not demonstrate oral activity. Quinoline analogs have improved upon the selectivity and pharmacokinetics of SCH 58261, but were difficult to handle due to poor aqueous solubility. We report the design and synthesis of fused heterocyclic analogs of SCH 58261 with aqueous solubility as well as improved A(2A) receptor binding selectivity and pharmacokinetic properties. In particular, the tetrahydronaphthyridine 4s has excellent A(2A) receptor in vitro binding affinity and selectivity, is active orally in a rat in vivo model of Parkinson's Disease, and has aqueous solubility of 100 mu M at physiological pH. (C) 2008 Elsevier Ltd. All rights reserved.