1,2,3,4-四氢异喹啉-7-甲腈 | 149355-52-2

• 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: 1,2,3,4-四氢异喹啉-7-甲腈
• 中文别名: 1,2,3,4-四氢异喹啉-7-腈；1,2,3,4-四氢-7-异喹啉甲腈
• 英文名称: 7-cyano-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 1,2,3,4-tetrahydroisoquinoline-7-carbonitrile
• CAS: 149355-52-2
• 化学式: C₁₀H₁₀N₂
• mdl: MFCD03094745
• 分子量: 158.203
• InChiKey: LJFNUFCUPDECPC-UHFFFAOYSA-N

物化性质

• 沸点：
  301.5±42.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 安全说明：
  S22
• 危险类别码：
  R20/21/22
• 海关编码：
  2933499090
• 危险品运输编号：
  UN 3439
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302,H312,H319,H332

反应信息

• 作为反应物：
  描述：

  1,2,3,4-四氢异喹啉-7-甲腈 在 盐酸 作用下， 反应 9.0h， 以93%的产率得到7-异喹啉甲酸
  参考文献：
  名称：

  Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

  摘要：

  7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the aa-adrenoceptor. To design a selective (PNMT vs alpha(2)-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha(2)-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pK(i) = 0.599 pi - 0.0725MR + 1.55 sigma(m) + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha(2)-adrenoceptor (alpha(2) pK(i) = 0.599 pi - 0.0542MR - 0.951 sigma(m) + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha(2)-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position, These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha(2)-adrenoceptor affinity) inhibitors of PNMT.

  DOI：

  10.1021/jm980429p
• 作为产物：
  描述：

  7-硝基-1,2,3,4-四氢异喹啉盐酸盐 在 platinum(IV) oxide 盐酸 、 sodium hydroxide 、 O₄S^(2-)*2Ni⁽¹⁺⁾ 、 氢气 、 sodium nitrite 作用下， 以 乙醇 为溶剂， 50.0 ℃ 、344.73 kPa 条件下， 反应 7.25h， 生成 1,2,3,4-四氢异喹啉-7-甲腈
  参考文献：
  名称：

  Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Toward Inhibition of Phenylethanolamine N-Methyltransferase vs the α₂-Adrenoceptor^1a

  摘要：

  7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha(2)-adrenoceptor (PNMT K-i = 0.55 mu M, alpha(2) K-i = 100 mu M, selectivity [alpha(2) K-i/PNMT K-i] = 180). A diverse set of compounds was synthesized and evaluated to probe the role of the acidic hydrogen of the aminosulfonyl group of 1 in imparting this selectivity. Compounds were designed to investigate the effect on selectivity of the acidity of the NH group [the 7-N-methyl (compound 5) and 7-N-(p-chlorophenyl) (compound 4) derivatives of 1], the relative spatial position of the acidic hydrogen [7-(N-(methylsulfonyl)amino)-1,2,3,4-tetrahydroisoquinoline (6) and 7-((N-(methylsulfonyl)amino)methyl)-1,2,3,4-tetrahydroisoquinoline (8)], or the effect of the substitution of an acidic phenolic group for the aminosulfonyl moiety [1-(aminomethyl)-6-hydroxynaphthalene (23) and 8-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline (9)]. All of the compounds studied displayed lower affinity for PNMT than I, and nine of the eleven compounds studied showed increased, rather than the desired decreased, affinity for the alpha(2)-adrenoceptor. Specifically, compound 4, in which the aminosulfonyl NH group is more acidic than that in 1, showed greatly reduced selectivity on account of increased alpha(2)-adrenoceptor affinity as compared to 1 (PNMT K-i = 2.6 mu M, alpha(2) K-i = 6.3 mu M, selectivity = 2.4). Compound 8, in which the acidic NH group is in the same region of space as that in 1, although the aminosulfonyl group is reversed with respect to the aromatic ring, showed poor PNMT affinity and modest alpha(2)-adrenoceptor affinity (PNMT K-i = 330 mu M, alpha(2) K-i = 18 mu M, selectivity = 0.055). Compound 9, in which a phenolic group is in the same region of space as the acidic NH of 1, exhibited the best alpha(2)-adrenoceptor affinity of any of the compounds studied (PNMT K-i = 0.98 mu M, alpha(2) K-i = 0.078 mu M, selectivity = 0.080). Results from this study suggest that the selectivity of 1 is not solely due to the presence of an acidic hydrogen on the 7-aminosulfonyl group of 1 but is likely also dependent on some other property (e.g.electron-withdrawing character) of the aminosulfonyl group.

  DOI：

  10.1021/jm960235e

文献信息

• Multicyclic bis-amide MMP inhibitors
  申请人：Powers Timothy

  公开号：US20060173183A1

  公开（公告）日：2006-08-03

  The present invention relates generally to bis-amide group containing pharmaceutical agents, and in particular, to multicyclic bis-amide MMP-13 inhibitor compounds. More particularly, the present invention provides a new class of MMP-13 inhibiting compounds, containing a pyrimidinyl bis-amide group in combination with a heterocyclic moiety, that exhibit an increased potency and solubility in relation to currently known bis-amide group containing MMP-13 inhibitors.

  本发明总体涉及含有双酰胺基团的药物制剂，特别是多环双酰胺MMP-13抑制剂化合物。更具体地，本发明提供了一类新型的MMP-13抑制化合物，它们含有与杂环部分结合的嘧啶基双酰胺基团，与目前已知含双酰胺基团的MMP-13抑制剂相比，显示出增加的活性和溶解度。
• PYRAZOLOPYRIDINE COMPOUNDS AND USES THEREOF
  申请人：Incyte Corporation

  公开号：US20180072720A1

  公开（公告）日：2018-03-15

  Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

  揭示了化合物的公式（I），使用这些化合物抑制HPK1活性的方法以及包含这些化合物的药物组合物。这些化合物在治疗、预防或改善与HPK1活性相关的疾病或紊乱方面是有用的，如癌症。
• Synthesis, evaluation and CoMFA/CoMSIA study of nitrofuranyl methyl N-heterocycles as novel antitubercular agents
  作者：Apeng Wang、Yang Yang、Yangsheng Jun、Bin Wang、Kai Lv、Mingliang Liu、Huiyuan Guo、Yu Lu

  DOI：10.1016/j.bmc.2018.03.004

  日期：2018.5

  chemical series employing comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) techniques. The developed CoMFA and CoMSIA models display high external predictability (r2pred of 0.954 and 0.935, respectively) and good statistical robustness. More importantly, the newly designed compounds 16a and 16b (MIC: <0.016 μg/mL) based on the two models, as expected

  设计并合成了一系列基于IIIM-MCD-211结构的新型硝基呋喃基甲基N-杂环。化合物6d，8b和12a对MTB H37Rv菌株表现出优异的活性（MIC：0.031–0.062μg/ mL），与INH和IIIM-MCD-211大致相当。此外，利用比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）技术对上述化学系列进行了三维定量构效关系（3D-QSAR）研究。已开发的CoMFA和CoMSIA模型显示出较高的外部可预测性（r 2 pred分别为0.954和0.935）和良好的统计稳健性。更重要的是，如预期的那样，发现基于两种模型的新设计的化合物16a和16b（MIC：<0.016μg/ mL）比12a和IIIM-MCD-21更具活性。目前正在进行更有效的硝基呋喃基甲基N-杂环化合物作为抗结核病药物的设计和合成。
• PYRAZOLOPYRIDINE PYRAZOLOPYRIMIDINE AND RELATED COMPOUNDS
  申请人：Global Blood Therapeutics, Inc.

  公开号：US20150315198A1

  公开（公告）日：2015-11-05

  In one aspect this invention relates generally to compounds of Formula: and sub-formulas thereof, or a tautomer of each thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, where X 1 , L 1 , L 3 , and R 3 are described herein.

  在一个方面，这项发明通常涉及以下式的化合物： 及其亚式，或每个亚式的重排异构体，每个的药学上可接受的盐，或每个前述的药学上可接受的溶剂，其中X 1 ，L 1 ，L 3 和R 3 如本文所述。
• Substituted bis-amide metalloprotease inhibitors
  申请人：Sucholeiki Irving

  公开号：US20070155739A1

  公开（公告）日：2007-07-05

  This invention relates to substituted bis-amide pyrimidine compounds of Formula (I), which are useful for the treatment of metalloprotease mediated diseases, in particular MMP-13 related diseases.

  这项发明涉及Formula (I)的取代双酰胺嘧啶化合物，这些化合物对于治疗金属蛋白酶介导的疾病，特别是MMP-13相关疾病是有用的。