6-methyl-3-(o-tolyl)isoquinolin-1(2H)-one | 203628-08-4

• 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: 6-methyl-3-(o-tolyl)isoquinolin-1(2H)-one
• 英文别名: 6-methyl-3-(2-methylphenyl)-2H-isoquinolin-1-one
• CAS: 203628-08-4
• 化学式: C₁₇H₁₅NO
• 分子量: 249.312
• InChiKey: JFNDUQYQBKMAEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 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：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-methyl-3-(o-tolyl)isoquinolin-1(2H)-one 在 sodium tetrahydroborate 、 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.0h， 生成 4-hydroxymethyl-2,6-dimethyl-3-o-tolyl-2H-isoquinolin-1-one
  参考文献：
  名称：

  通过Vilsmeier-Haack反应合成12-氧代苯并[ c ]菲啶酮和4-取代的3-芳基异喹啉酮

  摘要：

  在3-芳基异喹啉酮上进行Vilsmeier-Haack反应后，得到了多种多样的4-甲酰基化的3-芳基异喹啉酮，这些衍生物进一步衍生为12-氧代苯并[ c ]菲啶酮，4-烷氧基甲基-3-芳基异喹啉酮，3-芳基-4-苯氧基甲基异喹啉酮，4-氨基甲基- 3-芳基喹诺酮和3-异喹啉基-2-苯基-丙烯腈的合成策略不同。

  DOI：

  10.1016/j.tet.2011.10.053
• 作为产物：
  描述：

  2,4-二甲基苯甲酰氯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 6-methyl-3-(o-tolyl)isoquinolin-1(2H)-one
  参考文献：
  名称：

  通过Vilsmeier-Haack反应合成12-氧代苯并[ c ]菲啶酮和4-取代的3-芳基异喹啉酮

  摘要：

  在3-芳基异喹啉酮上进行Vilsmeier-Haack反应后，得到了多种多样的4-甲酰基化的3-芳基异喹啉酮，这些衍生物进一步衍生为12-氧代苯并[ c ]菲啶酮，4-烷氧基甲基-3-芳基异喹啉酮，3-芳基-4-苯氧基甲基异喹啉酮，4-氨基甲基- 3-芳基喹诺酮和3-异喹啉基-2-苯基-丙烯腈的合成策略不同。

  DOI：

  10.1016/j.tet.2011.10.053

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
• 신규한 디아릴이소퀴놀론 또는 디아릴이소퀴놀린 화합물 및 이를 포함하는 약제학적 조성물
  申请人：INDUSTRY FOUNDATION OF CHONNAM NATIONAL UNIVERSITY 전남대학교산학협력단(220040365775) BRN ▼409-82-11942

  公开号：KR20170049742A

  公开（公告）日：2017-05-11

  본 발명은 신규한 디아릴이소퀴놀론(diarylisoquinolones) 또는 디아릴이소퀴놀린(diarylisoquinolines) 화합물에 관한 것이다. 본 발명의 화합물은 암세포인 인간 유관 상피암 세포주(T47D), 인간 전립선암 세포주(DU145) 및 인간 직장 선암종 세포주(HCT-15)에서 선택적인 세포독성을 나타내고, 특히 기존의 topo 억제제인 CPT 및 에토포사이드(etoposide)과 비교하여 우수한 억제효과를 나타낸다. 또한, 본 발명의 화합물 중 3,4-디아릴이소퀴놀론은 topo Ⅱ에 대한 억제활성을 나타내고, 3,4-디아릴이소퀴놀린아민은 우수한 topo I 억제활성을 나타내며, 이를 이용하여 디아릴-치환된 이소퀴놀린을 항암제로 사용할 수 있음을 증명하였다.

  本发明涉及新型二芳基异喹诺酮（diarylisoquinolones）或二芳基异喹啉（diarylisoquinolines）化合物。本发明的化合物在人类乳腺上皮癌细胞系（T47D）、人类前列腺癌细胞系（DU145）以及人类结直肠癌细胞系（HCT-15）中表现出选择性的细胞毒性，并且与现有的拓扑异构酶抑制剂CPT和依托泊苷（etoposide）相比，显示出更优越的抑制效果。此外，本发明中的3,4-二芳基异喹诺酮表现出对拓扑异构酶II的抑制活性，而3,4-二芳基异喹啉酰胺则显示出优秀的拓扑异构酶I抑制活性，这证明了可以利用这些二芳基取代的异喹啉作为抗癌药物。
• 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.