1-chloro-6-methyl-3-(2-methylphenyl)isoquinoline | 220631-02-7

• 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: 1-chloro-6-methyl-3-(2-methylphenyl)isoquinoline
• 英文别名: 1-chloro-6-methyl-3-(o-tolyl)isoquinoline；1-chloro-6-methyl-3-o-tolylisoquinoline
• CAS: 220631-02-7
• 化学式: C₁₇H₁₄ClN
• 分子量: 267.758
• InChiKey: IHFHAALUMGLSQC-UHFFFAOYSA-N

物化性质

• 沸点：
  400.1±40.0 °C(Predicted)
• 密度：
  1.181±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-chloro-6-methyl-3-(2-methylphenyl)isoquinoline 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 66.0 ℃ 、620.53 kPa 条件下， 反应 78.0h， 生成 6-methyl-3-o-tolylisoquinolin-1-ylamine
  参考文献：
  名称：

  Molecular modeling of 3-arylisoquinoline antitumor agents active against A-549. A comparative molecular field analysis study

  摘要：

  A series of 58 3-arylisoquinoline antitumor agents were investigated for defining the pharmacophore model using comparative molecular field analysis (CoMFA) program. The studied compounds related to bioisostere of benzophenanthridine alkaloid were synthesized and evaluated for antitumor cytotoxicity against human lung tumor cell (A 549). In order to perform the systematic molecular modeling study of these compounds, the conformational search was carried out based on the single X-ray crystallographic structure of 7,8-dimethoxy-3-phenylisoquinolin-(2H)-one (2). Interestingly, two types of structures having different dihedral angles between the isoquinoline ring and 3-aryl ring were found in the crystals. Therefore, CoMFA was performed two different, overlapping ways. The alignments of the structures were based on the common isoquinoline ring and 3-aryl ring. The 3-D-quantitative structure-activity relationship study resulted in significant cross-validated, conventional r(2) values equal to 0.715 and 0.927, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00137-2
• 作为产物：
  描述：

  6-methyl-3-(o-tolyl)isoquinolin-1(2H)-one 在 三氯氧磷 作用下， 生成 1-chloro-6-methyl-3-(2-methylphenyl)isoquinoline
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents

  摘要：

  To investigate the structure-activity relationship of 7,8-dimethoxy-2-methyl-3-(4,5-methylenedioxy-2-vinylphenyl)isoquinolin-1(2H)-one 2, diverse substituted 3-arylisoquinolines were synthesized and tested in vitro antitumor activity against five human tumor cell lines. The results showed a broad antitumor spectrum for a series of 3-arylisoquinolines. (C) 1997 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(97)10190-1

文献信息

• Modification of 3-arylisoquinolines into 3,4-diarylisoquinolines and assessment of their cytotoxicity and topoisomerase inhibition
  作者：Daulat Bikram Khadka、Hyunjung Woo、Su Hui Yang、Chao Zhao、Yifeng Jin、Thanh Nguyen Le、Youngjoo Kwon、Won-Jea Cho

  DOI：10.1016/j.ejmech.2015.01.016

  日期：2015.3

  Isoquinolinamine derivatives had greater affinity for topo I than for topo II. Topo inhibition by 3,4-diarylisoquinolines was further supported by docking models showing intercalative and/or H-bond interactions between these compounds and the DNA/topo(s). An analysis of the correlation between the cytotoxicity and topo inhibition of these compounds indicated that the primary biological target of derivatives with

  受到单芳基异喹啉的初步成功的启发，并寻求寻找具有拓扑异构酶（拓扑）抑制活性的更有效和选择性的抗癌药，设计并合成了一系列二芳基异喹啉（3,4-二芳基异喹啉酮和3,4-二芳基异喹啉胺）。这些化合物的合成主要涉及锂化甲苯酰胺-苄腈的环加成，Suzuki偶联和亲核芳族取代反应。其中八种衍生物对人乳腺导管上皮肿瘤细胞（T47D），人前列腺癌细胞（DU145）和人结肠直肠腺癌细胞（HCT-15）有选择性毒性，但对正常人乳腺上皮细胞（MCF10A）没有影响。二芳基异喹啉化合物的拓扑抑制活性相对取决于它们的化学结构。3，4-二芳基异喹诺酮类通常不抑制topo I，而仅表现出对topo II的中等抑制作用。相反，几种3,4-二芳基异喹啉胺显示出优异的topo I抑制活性。异喹啉胺衍生物对topo I的亲和力大于对topo II的亲和力。对接模型进一步支持了3,4-二芳基异喹啉对拓扑的抑制作用，该模型显示了这些化合物与DNA
• Synthesis, in vitro and in vivo evaluation of 3-arylisoquinolinamines as potent antitumor agents
  作者：Su Hui Yang、Hue Thi My Van、Thanh Nguyen Le、Daulat Bikram Khadka、Suk Hee Cho、Kyung-Tae Lee、Hwa-Jin Chung、Sang Kook Lee、Chang-Ho Ahn、Young Bok Lee、Won-Jea Cho

  DOI：10.1016/j.bmcl.2010.06.132

  日期：2010.9

  In the search for potent water-soluble 3-arylisoquinolines, several 3-arylisoquinolinamines were designed and synthesized. Various substituted 3-arylisoquinolinamines exhibited strong cytotoxic activity against eight different human cancer cell lines. In particular, C-6 or C-7 dimethylamino-substituted 3-arylisoquinolinamines displayed stronger potency than the lead compound 7a. Interestingly, compounds 7b and 7c showed more effective activity against paclitaxel-resistant HCT-15 human colorectal cancer cell lines when compared to the original cytotoxic cancer drug, paclitaxel. We analyzed the cell cycle dynamics by flow cytometry and found that treatment of human HCT-15 cells with 3-arylisoquinolinamine 7b blocked or delayed the progression of cells from G0/G1 phase into S phase, and induced cell death. Treatment with compound 7b also significantly inhibited the growth of tumors and enhanced tumor regression in a paclitaxel-resistant HCT-15 xenograft model. (C) 2010 Elsevier Ltd. All rights reserved.
• Development of 3-aryl-1-isoquinolinamines as potent antitumor agents based on CoMFA
  作者：Su Hui Yang、Hue Thi My Van、Thanh Nguyen Le、Daulat Bikram Khadka、Suk Hee Cho、Kyung-Tae Lee、Eung-Seok Lee、Young Bok Lee、Chang-Ho Ahn、Won-Jea Cho

  DOI：10.1016/j.ejmech.2010.08.042

  日期：2010.11

  Various substituted 3-aryl-1-isoquinolinamines were designed and synthesized based on the previously constructed CoMFA model. Most of the synthesized compounds showed excellent potency in eight different human tumor cell lines as expected. In order to find the exact cytotoxic mechanism of these 3-aryl-1-isoquinolinamines, we analyzed the cell cycle dynamics by flow cytometry and found that 3-aryl-1-isoquinolinamine 6k-treated HeLa cells were arrested in G2/M phase, which is related to apoptosis. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives
  作者：Won-Jea Cho、Eui-Ki Kim、Myun-Ji Park、Sang-Un Choi、Chong-Ock Lee、Seung Hoon Cheon、Bo-Gil Choi、Byung-Ho Chung

  DOI：10.1016/s0968-0896(98)80019-9

  日期：1998.12

  In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r(2) as high as 0.721) was obtained through CoMFA, (C) 1998 Elsevier Science Ltd. All rights reserved.