(1S,3S)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | 41565-89-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (1S,3S)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline
• CAS: 41565-89-3
• 化学式: C₁₁H₁₅N
• 分子量: 161.247
• InChiKey: OASVVFGGGPJVPM-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (1S,3S)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline 在 硫酸 、 potassium nitrate 作用下， 生成 trans-1,3-dimethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  1,3-二甲基-7-取代的1,2,3,4-四氢异喹啉作为探针检测四氢异喹啉在苯乙醇胺N-甲基转移酶活性位点的结合方向。

  摘要：

  为了确定肾上腺素（Epi）在中枢神经系统中的功能，我们针对了催化Epi的生物合成最后一步的酶，即苯乙醇胺N-甲基转移酶（PNMT; EC 2.1.1.28）。1,2,3,4-四氢异喹啉（THIQs）是该酶的抑制剂，但对α2-肾上腺素受体也表现出亲和力。为了进一步了解THIQs在PNMT活性位点上的结合方式，并试图进一步提高THIQ型抑制剂相对于α2-肾上腺素受体的选择性，一系列顺式和反式1,3-二甲基-7取代-THIQ合成。对这些化合物的评估表明，基于7位取代基的亲脂性，THIQs在PNMT活性位点以两种不同的方向结合。然而，

  DOI：

  10.1016/s0968-0896(99)00031-0
• 作为产物：
  描述：

  (1S)-1-methyl-N-[(S)-1-phenylethyl]-2-phenylsulfanylethylamine 在 sodium hydroxide 、 sodium tetrahydroborate 、 sodium periodate 、 乙酸酐 、 三氟乙酸 、 nickel dichloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 苯 为溶剂， 反应 46.17h， 生成 (1S,3S)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Toda, Jun; Matsumoto, Shinobu; Saitoh, Toshiaki, Chemical and pharmaceutical bulletin, 2000, vol. 48, # 1, p. 91 - 98

  摘要：

  DOI：

文献信息

• Super Acid-Induced Pummerer-Type Cyclization Reaction: Improvement in the Synthesis of Chiral 1,3-Dimethyl-1,2,3,4-tetrahydroisoquinolines
  作者：Toshiaki Saitoh、Kentaro Shikiya、Yoshie Horiguchi、Takehiro Sano

  DOI：10.1248/cpb.51.667

  日期：——

  Improved synthesis of four stereoisomeric chiral 1,3-dimethyl-1,2,3,4-tetrahydroisoquinolines (1a, b, ent-1a, b) was achieved via the super acid-induced cyclization of chiral N-[1-methyl-2-(phenylsulfinyl)ethyl]-N-(1-phenylethyl)formamides (4a, b, ent-4a, b) using the Pummerer-type cyclization reaction as a key step. The cyclization leading to the isoquinoline ring proceeded in a quantitative manner

  通过超强酸诱导的手性N- [1-甲基-使用Pummerer型环化反应作为关键步骤，制得2-（苯亚磺酰基）乙基] -N-（1-苯乙基）甲酰胺（4a，b，ent-4a，b）。当使用三氟甲烷磺酸（TFSA）作为过酸时，导致异喹啉环的环化以定量方式进行，尽管4-苯硫基TIQ衍生物（5）的Friedel-Crafts型烷基化以苯为溶剂伴随着环化得到4-苯基-TIQ（7）。当使用大量过量的TFSA时，仅形成副产物（7）。
• Conformational Analysis. 50. <i>C</i>-Methyl-1,2,3,4-tetrahydroisoquinolines
  作者：Edward M. Olefirowicz、Ernest L. Eliel

  DOI：10.1021/jo971257r

  日期：1997.12.1

  Conformational equilibria in 1-, 3-, and 4-methyl-1,2,3,4-tetrahydroisoquinolines (THIQs) and the diastereomeric pairs of their 1,3- and 1,4-dimethyl homologs have been determined by measurement of H-3/H-4(trans) coupling constants and have been confirmed by molecular mechanics [MMP2(85]) calculations. The experimental -Delta G degrees values (a --> e) for the monomethyl compounds (computed values in parentheses) in kcal mol(-1) are Me-1, 0.56 (0.46); Me-3, 1.63 (1.53); and Me-4, -0.32 (-0.22). Agreement of experimental and calculated values is very goad as is the additivity of values for the dimethyl compounds (Table 1). Values for the corresponding hydrochlorides are Me-1, 0.19 (-0.34); Me-3, 1.15 (1.46); and Me-4, 0.35 (0.10) kcal mol(-1). The less than satisfactory agreement of experimental with computed data here is probably due to neglect of solvation. The very small or negative Delta G degrees values for Me-1 and Me-4 were ascribed not only to the pseudoaxial (rather than axial) nature of Me(ax) and the absence of a syn-axial hydrogen on the side of the benzene ring but also to a peri interaction with H(8) and H(5), respectively, destabilizing equatorial methyl at positions 1 and 4. This was confirmed by comparing computed conformational energy values with values at corresponding positions in Delta(3,4)-tetrahydropyridines (THPs). While Delta G degrees in the two series is the same for Me-3 (THIQ numbering), that for Me-1 and Me-4 is considerably smaller in the THIQ than in the THP series which latter is devoid of peri hydrogens.
• GAPDH CASCADE INHIBITOR COMPOUNDS AND METHODS OF USE AND TREATMENT OF STRESS INDUCED DISORDERS INCLUDING MENTAL ILLNESS
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US20170087145A1

  公开（公告）日：2017-03-30

  In DN-DISC1 mice, a mouse model for major mental illnesses, the model that expresses pathological phenotypes relevant to schizophrenia, mood disorders, and addiction simultaneously, the inventors of the present invention found pronounced levels of oxidative stress in the prefrontal cortex, but not in the striatum. These mice also displayed greater amounts of GAPDH-Siah1 binding, a protein-protein interaction that is activated under exposure to oxidative stress. The present inventors investigated the role of oxidative stress in other organ systems. As detailed herein, the inventors found that GAPDH-Siah1 binding was increased in mouse models of cardiac failure. It was also found, that certain novel analogs of deprenyl, significantly inhibited GAPDH-Siah1 binding in cardiac tissue. Thus, with experimental data provided herein, it is clear that this GAPDH-Siah1 binding cascade is a crucial mechanism involved in major mental illness, such as schizophrenia, mood disorders, and addiction, as well as in stress-associated diseases involving other organs where GAPDH is expressed. The present invention provides compounds and composition comprising analogs of deprenyl and their use in the inhibition of nuclear GAPDH-Siah1 binding and the activation of p300 and MEF2. Also provided herein are methods of prevention and treatment of stress induced disorders of the body, including, for example, major mental illness, such as schizophrenia, mood disorders, and addiction, as well as in stress-associated diseases involving other organs, such as cardiac hypertrophy, in vivo, comprising administering to a mammal a therapeutically effective amount of analogs of deprenyl.
• 1,3-Dimethyl-7-substituted-1,2,3,4-tetrahydroisoquinolines as probes for the binding orientation of tetrahydroisoquinoline at the active site of phenylethanolamine N-methyltransferase[1]
  作者：Gary L. Grunewald、Timothy M. Caldwell、Qifang Li、Kevin R. Criscione

  DOI：10.1016/s0968-0896(99)00031-0

  日期：1999.5

  in the biosynthesis of Epi, phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28). 1,2,3,4-Tetrahydroisoquinolines (THIQs) are inhibitors of this enzyme, but also display affinity for the alpha2-adrenoceptor. To gain further understanding about how THIQs bind at the PNMT active site and in an attempt to further increase the selectivity of THIQ-type inhibitors versus the alpha2-adrenoceptor, a series

  为了确定肾上腺素（Epi）在中枢神经系统中的功能，我们针对了催化Epi的生物合成最后一步的酶，即苯乙醇胺N-甲基转移酶（PNMT; EC 2.1.1.28）。1,2,3,4-四氢异喹啉（THIQs）是该酶的抑制剂，但对α2-肾上腺素受体也表现出亲和力。为了进一步了解THIQs在PNMT活性位点上的结合方式，并试图进一步提高THIQ型抑制剂相对于α2-肾上腺素受体的选择性，一系列顺式和反式1,3-二甲基-7取代-THIQ合成。对这些化合物的评估表明，基于7位取代基的亲脂性，THIQs在PNMT活性位点以两种不同的方向结合。然而，
• Toda, Jun; Matsumoto, Shinobu; Saitoh, Toshiaki, Chemical and pharmaceutical bulletin, 2000, vol. 48, # 1, p. 91 - 98
  作者：Toda, Jun、Matsumoto, Shinobu、Saitoh, Toshiaki、Sano, Takehiro

  DOI：——

  日期：——