9-chloro-4-methylacridine-5-dimethylaminoethylcarboxamide | 253277-91-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 9-chloro-4-methylacridine-5-dimethylaminoethylcarboxamide
• 英文别名: 9-chloro-5-methylacridan-4-dimethylaminoethylcarboxamide；4-Acridinecarboxamide, 9-chloro-N-[2-(dimethylamino)ethyl]-5-methyl-；9-chloro-N-[2-(dimethylamino)ethyl]-5-methylacridine-4-carboxamide
• CAS: 253277-91-7
• 化学式: C₁₉H₂₀ClN₃O
• 分子量: 341.84
• InChiKey: UAHKUFNIIVPMQV-UHFFFAOYSA-N

物化性质

• 沸点：
  578.8±40.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  9-chloro-4-methylacridine-5-dimethylaminoethylcarboxamide 在 氨 作用下， 以 various solvent(s) 为溶剂， 反应 0.25h， 生成 4-Acridinecarboxamide, 9-amino-N-[2-(dimethylamino)ethyl]-5-methyl-
  参考文献：
  名称：

  Potential antitumor agents. 46. Structure-activity relationships for acridine monosubstituted derivatives of the antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide

  摘要：

  A series of monosubstituted derivatives of the new antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide has been prepared, bearing methyl, methoxy, and chloro groups at available acridine positions. The physicochemical properties and antitumor activity of these compounds varied more with the position than with the nature of the substituent groups. The highest levels of both in vitro and in vivo antileukemic activity were shown by 5-substituted derivatives, while 7- and 8-substituted derivatives possessed the highest selectivity toward the HCT-8 human colon carcinoma line compared to the L1210 mouse leukemia line in vitro.

  DOI：

  10.1021/jm00154a008
• 作为产物：
  描述：

  9,10-dihydro-5-methyl-9-oxo-4-acridinecarboxylic acid 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 9-chloro-4-methylacridine-5-dimethylaminoethylcarboxamide
  参考文献：
  名称：

  Potential antitumor agents. 46. Structure-activity relationships for acridine monosubstituted derivatives of the antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide

  摘要：

  A series of monosubstituted derivatives of the new antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide has been prepared, bearing methyl, methoxy, and chloro groups at available acridine positions. The physicochemical properties and antitumor activity of these compounds varied more with the position than with the nature of the substituent groups. The highest levels of both in vitro and in vivo antileukemic activity were shown by 5-substituted derivatives, while 7- and 8-substituted derivatives possessed the highest selectivity toward the HCT-8 human colon carcinoma line compared to the L1210 mouse leukemia line in vitro.

  DOI：

  10.1021/jm00154a008

文献信息

• 5-(9-ACRIDINYLAMINO)-TOLUIDINE COMPOUNDS
  申请人：——

  公开号：US20040198765A1

  公开（公告）日：2004-10-07

  This invention relates to 9-anilinoacridine compounds, and more particularly to their synthesis and their use in pharmaceutical compositions for treating diseases.

  这项发明涉及9-苯胺基吖啶化合物，更具体地涉及它们的合成以及它们在制备治疗疾病的药物组合物中的应用。
• 9-anilinoacridine alkylating agents
  申请人：Su Tsann-Long

  公开号：US20080176889A1

  公开（公告）日：2008-07-24

  This invention relates to 9-anilinoacridine alkylating agents, their synthesis and their use in pharmaceutical compositions for treating diseases.

  这项发明涉及9-苯胺基吖啶烷基化剂，它们的合成以及它们在治疗疾病的药物组合物中的应用。
• Potent antitumor 9-anilinoacridines bearing an alkylating N-mustard residue on the anilino ring: synthesis and biological activity
  作者：Valeriy A. Bacherikov、Ting-Chao Chou、Hua-Jin Dong、Xiuguo Zhang、Ching-Huang Chen、Yi-Wen Lin、Tsong-Jen Tsai、Rong-Zau Lee、Leroy F. Liu、Tsann-Long Su

  DOI：10.1016/j.bmc.2005.03.057

  日期：2005.6

  A series of N-mustard derivatives of 9-anilinoacridine was synthesized for antitumor and structure-activity relationship studies. The alkylating N-mustard residue was linked to the C-3' or C-4' position of the anilino ring with an O-ethylene (O-C-2) O-butylene (O-C-4), and methylene (C-1) spacer. All of the new N-mustard derivatives exhibited significant cytotoxicity in inhibiting human lymphoblastic leukemic cells (CCRF-CEM) in culture. Of these agents, (3-(acridin-9-ylamino)-5-2-[bis(2-chloroethyl)amino]ethoxy}phenyl)methanol (10) was subjected to antitumor studies, resulting in an approximately 100-fold more potent effect than its parent analogue 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) in inhibiting the growth of human lymphoblastic leukemic cells (CCRF-CEM) in vitro. This agent did not exhibit cross-resistance against vinblastine-resistant (CCRF-CEM/VBL) or Taxol-resistant (CCRF-CEM/Taxol) cells. Remarkably, the therapeutic effect of 10 at a dose as low as one tenth of the Taxol therapeutic dose [i.e., 1-2 mg/kg (Q3D x 7) or 3 mg/kg (Q4D x 5); intravenous injection] on nude mice bearing human breast carcinoma MX-1 xenografts resulted in complete tumor remission in two out of three mice. Furthermore, 10 yielded xenograft tumor suppression of 81-96% using human T-cell acute lymphoblastic leukemia CCRF-CEM, colon carcinoma HCT-116, and ovarian adenocarcinoma SK-OV-3 tumor models. (c) 2005 Elsevier Ltd. All rights reserved.
• New analogues of AHMA as potential antitumor agents: synthesis and biological activity
  作者：Jang-Yang Chang、Chyun-Feng Lin、Wen-Yu Pan、Valeriy Bacherikov、Ting-Chao Chou、Ching-Huang Chen、Huajin Dong、Shu-Yun Cheng、Tsong-Jen Tasi、Yi-Wen Lin、Kuo-Tung Chen、Li-Tzong Chen、Tsann-Long Su

  DOI：10.1016/j.bmc.2003.09.001

  日期：2003.11

  A series of new analogues of 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA, 1) and AHMA-ethylcarbamate (2) were synthesized by introducing an O-alkylcarboxylic acid esters to the CH2OH function, displacing the CH2OH function with a dimethylaminocarboxamido group or with a methyl function introduced at the meta-, para- or ortho-position to the NH2 group to form 5-(9-acridinylamino)-m-toluidines (AMTs), 5-(9-acridinylamino)-p-toluidines (APTs) or 5-(9-acridinylamino)-o-toluidines (AOTs), respectively. The inhibitions of a variety of human tumor cell growth, interactions with DNA as well as inhibitory effect against topoisomerase 11 (Topo 11) of these new agents were studied. Among AMT, APT and AOT derivatives with dimethylaminoethylcarboxamido and Me at C4 and C5 of acridine moiety (i.e., 21c, 23c and 26c) were more cytotoxic than AHMA (1) and AHMA-ethylcarbamate (2), depending upon the tumor cell line tested. Detailed structure-activity relationships of the new analogues were studied. (C) 2003 Elsevier Ltd. All rights reserved.
• Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation
  作者：Valeriy A. Bacherikov、Ting-Chao Chou、Hua-Jin Dong、Ching-Huang Chen、Yi-Wen Lin、Tsong-Jen Tsai、Tsann-Long Su

  DOI：10.1016/j.bmcl.2004.06.080

  日期：2004.9

  A series of 9-anilinoacridine N-mustard derivatives, in which the alkylating N-mustard residue was linked to the C-3' or C-4' position of the anilino ring with an O-ethylene spacer, was synthesized and evaluated for cytotoxicity against human lymphoblastic leukemic cells (CCRF-CEM) in culture. The results showed that all of the new compounds exhibited potent cytotoxicity with IC50 values ranging from 0.002 to 0.7 muM, which were as potent or significantly more potent than 3-(9-acridinylamino)-5-hydroxy-methylaniline (AHMA). Compound 9 did not exhibit cross-resistance against both vinblastine-resistant (CCRF-CEM/VBL) and taxol-resistant (CCRF-CEM/taxol) cells. Additionally, compound 9 demonstrated potent antitumor effect in nude mice bearing human breast carcinoma MX-1 xenografts, resulting in complete tumor remission in two out of three mice at the maximal dose of 1-2 mg/kg (Q3Dx7) or 3 mg/kg (Q4Dx5) via intravenous injection. (C) 2004 Elsevier Ltd. All rights reserved.