3-chloro-1-methyl-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile | 17012-31-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-chloro-1-methyl-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile
• 英文别名: 3-Chlor-4-cyan-1-methyl-5,6,7,8-tetrahydroisochinolin；3-Chloro-4-cyano-1-methyl-5,6,7,8-tetrahydroisoquinoline
• CAS: 17012-31-6
• 化学式: C₁₁H₁₁ClN₂
• mdl: MFCD01957409
• 分子量: 206.675
• InChiKey: FYNCNVGZPPZNPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-1-methyl-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile 在 sodium methylate 作用下， 以 N-甲基乙酰胺 、 甲醇 、 水 为溶剂， 生成 4-cyano-3-methoxy-1-methyl-5,6,7,8-tetrahydroisoquinoline
  参考文献：
  名称：

  Herbicidal cyclohexane-1,3-dione derivatives

  摘要：

  公式为##STR1##的化合物，其中：R.sup.5是双环芳基或含氮杂芳基环系统，如萘基、喹啉基、异喹啉基或四氢异喹啉基，可选择性地被各种基团取代；R.sup.4和R.sup.1最好是氢，但也可以是其他基团，R.sup.2和R.sup.3选自烷基、卤代烷基、烯基、卤代烯基和炔基，在对许多广叶作物具有高度杀草活性的同时，对一些小粒谷物具有良好的选择性。描述了制备公式I化合物的方法，制备公式I化合物的中间体以及公式I化合物的除草性能。

  公开号：

  US04640708A1
• 作为产物：
  描述：

  4-cyano-3-methoxy-1-methyl-5,6,7,8-tetrahydroisoquinoline 在 N,N-二甲基甲酰胺 、 三氯氧磷 作用下， 以70%的产率得到3-chloro-1-methyl-5,6,7,8-tetrahydroisoquinoline-4-carbonitrile
  参考文献：
  名称：

  A Novel Transformation of 3-Alkoxyisoquinolines to 3-Chloroisoquinolines and an Unusual Decyanation of 1,3-Dialkoxy-4-cyano-5,6,7,8-tetrahydroisoquinolines Under Vilsmeier-Haack Conditions

  摘要：

  DOI：

  10.1055/s-1984-30954

文献信息

• Development of dual inhibitors targeting pyruvate dehydrogenase kinases and human lactate dehydrogenase A: High-throughput virtual screening, synthesis and biological validation
  作者：Sichuan Xiang、Ding Huang、Qiaolin He、Jie Li、Kin Yip Tam、Shao-Lin Zhang、Yun He

  DOI：10.1016/j.ejmech.2020.112579

  日期：2020.10

  Pyruvate dehydrogenase kinases (PDKs) and lactate dehydrogenase A (LDHA) play crucial roles in promotion of glycolysis, thus the inhibition of both enzymes is considered a promising strategy for developing of anticancer therapeutics. Herein, we describe the first discovery of series novel dual inhibitors targeting PDKs and LDHA. We identified 6 hits from a library database containing 485465 compounds through

  大多数癌细胞具有从氧化磷酸化到细胞质糖酵解的葡萄糖代谢改变的特征。丙酮酸脱氢酶激酶（PDKs）和乳酸脱氢酶A（LDHA）在促进糖酵解中起关键作用，因此抑制这两种酶被认为是开发抗癌治疗剂的有希望的策略。在这里，我们描述了针对PDK和LDHA的系列新型双重抑制剂的首次发现。通过高通量虚拟筛选分析，我们从包含485465种化合物的数据库数据库中鉴定了6个匹配项。领先的优化方法使我们能够发现两种化合物，即20e和20k，它们分别抑制了IC 50值为0.8和1.6μM的PDK，并抑制了IC 50的LDHA。值分别为0.15和0.7μM。同时，这两种化合物降低了A549细胞的增殖，EC 50值为13.2和15.7μM。此外，20e和20k减少了乳酸的形成，增加了氧气的消耗，表明这两种化合物调节了癌细胞中的葡萄糖代谢途径。
• Herbicidal cyclohexane-1,3-dione-5-isoquinoline derivatives
  申请人：ICI Australia Limited

  公开号：US04680400A1

  公开（公告）日：1987-07-14

  The invention concerns novel compounds of the formula I ##STR1## wherein: A, B, D and E are selected from CH, N and N-Z wherein Z is selected from oxygen and the group YAn wherein Y is selected from alkyl and benzyl and An is an anion, and provided that no more than three of A, B, D and E are selected from N and N-Z and no more than one of A, B, D and E is selected from N-Z; W is a saturated or unsaturated C.sub.2 to C.sub.5 hydrocarbon chain; X and X.sup.1 are independently selected from halogen, nitro, cyano, alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, alkenyl, alkenyloxy, alkynyl, alkynyloxy, acyloxy, alkoxycarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, sulfamoyl, substituted sulfamoyl, alkanoyloxy, benzyloxy, substituted benzyloxy, amino, substituted amino and the groups formyl and alkanoyl and the oxime, imine and Schiff base derivatives thereof, or two of X.sup.1 on the same carbon atom may form an oxo group; R.sup.1 is selected from hydrogen, alkyl, alkenyl, alkynyl, substituted alkyl, alkylsulfonyl, arylsulfonyl, acyl and an inorganic or organic cation; R.sup.2 is selected from alkyl, substituted alkyl, alkenyl, haloalkenyl, alkynyl and haloalkynyl; R.sup.3 is selected from alkyl, fluoroalkyl, alkenyl, alkynyl, and phenyl; R.sup.4 is selected from hydrogen, halogen, alkyl, cyano and alkoxycarbonyl; n is 0 or an integer chosen from 1 to 3; and n.sup.1 is 0 or an integer chosen from 1 to 5. The compounds of the invention show herbicidal properties and plant growth regulating properties and in further embodiments the invention provides processes for the preparation of compounds of formula I, intermediates useful in the preparation of the compounds of formula I, compositions containing as active ingredient a compound of formula I, and herbicidal and plant growth regulating processes utilizing compounds of formula I.

  本发明涉及化合物I的新型化合物，其化学式为：##STR1##其中：A、B、D和E选择自CH、N和N-Z，其中Z选择自氧和YAn基团，其中Y选择自烷基和苯甲基，An是阴离子，并且保证A、B、D和E中最多只有三个选择自N和N-Z，最多只有一个选择自N-Z；W是饱和或不饱和的C.sub.2至C.sub.5烃基链；X和X.sup.1独立选择自卤素、硝基、氰基、烷基、取代烷基、羟基、烷氧基、取代烷氧基、烯基、烯氧基、炔基、炔氧基、酰氧基、烷氧羰基、烷基硫基、烷基亚磺酰基、烷基磺酰基、磺酰胺基、取代磺酰胺基、烷酰氧基、苄氧基、取代苄氧基、氨基、取代氨基和甲酰基和烷酰基及其氧肟、亚胺和席夫碱衍生物，或X.sup.1中的两个在同一碳原子上可以形成氧代基；R.sup.1选择自氢、烷基、烯基、炔基、取代烷基、烷基磺酰基、芳基磺酰基、酰基和无机或有机阳离子；R.sup.2选择自烷基、取代烷基、烯基、卤代烯基、炔基和卤代炔基；R.sup.3选择自烷基、氟烷基、烯基、炔基和苯基；R.sup.4选择自氢、卤素、烷基、氰基和烷氧羰基；n为0或从1到3选择的整数；n.sup.1为0或从1到5选择的整数。本发明的化合物具有除草和植物生长调节性能，在进一步实施中，本发明提供了制备化合物I的工艺、制备化合物I的中间体、含有化合物I作为活性成分的组合物以及利用化合物I进行除草和植物生长调节的过程。
• Synthesis and evaluation of pyrido-thieno-pyrimidines as potent and selective Cdc7 kinase inhibitors
  作者：Chunlin Zhao、Christian Tovar、Xuefeng Yin、Qui Xu、Ivan T. Todorov、Lyubomir T. Vassilev、Li Chen

  DOI：10.1016/j.bmcl.2008.11.093

  日期：2009.1

  Cdc7 kinase plays a critical role in the regulation of DNA replication in eukaryotic cells and has been proposed as a target for cancer therapy. We have identified a class of Cdc7/Dbf4 inhibitors with a pyrido-thieno-pyrimidine core structure. Synthesis of a focused pyrido-thieno-pyrimidine library yielded potent and selective Cdc7 inhibitors with antiproliferative activity against cancer cells in vitro. Their synthesis and SAR data are presented herein. (C) 2008 Elsevier Ltd. All rights reserved.
• ——
  作者：E. G. Paronikyan、S. N. Sirakanyan、A. S. Noravyan、R. G. Paronikyan、I. A. Dzhagatspanyan

  DOI：10.1023/a:1010438307254

  日期：——
• KASTURI, T. R.;JOIS, H. R. Y.;MATHEW, L., SYNTHESIS, BRD, 1984, N 9, 743-746
  作者：KASTURI, T. R.、JOIS, H. R. Y.、MATHEW, L.

  DOI：——

  日期：——