3-氯-6-(三氟甲基)喹喔啉-2-羧酸乙酯 | 194423-80-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 3-氯-6-(三氟甲基)喹喔啉-2-羧酸乙酯
• 英文名称: ethyl 3-chloro-6-(trifluoromethyl)quinoxaline-2-carboxylate
• 英文别名: Ethyl 3-chloro-6-(trifluoromethyl)quinoxaline-2-carboxylate
• CAS: 194423-80-8
• 化学式: C₁₂H₈ClF₃N₂O₂
• 分子量: 304.656
• InChiKey: PKAZXROSEIOTBH-UHFFFAOYSA-N

物化性质

• 沸点：
  340.1±37.0 °C(Predicted)
• 密度：
  1.451±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-氯-6-(三氟甲基)喹喔啉-2-羧酸乙酯 在 sodium hydroxide 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成
  参考文献：
  名称：

  喹喔啉化学。第十七部分。甲基[4-（取代的2-喹喔啉基氧基）苯基]乙酸甲酯和N-（[4-（取代的2-喹喔啉基氧基）苯基]乙酰基）谷氨酸乙酯的甲氨蝶呤类似物：合成和评价体外抗癌活性。

  摘要：

  在NCI上从本论文中描述的21种喹喔啉衍生物中选择了14种，以评估其体外抗癌活性。初步筛选显示，某些衍生物在10（-5）和10（-4）M浓度之间的各种肿瘤细胞系上均表现出中等至强的生长抑制活性。还记录了化合物9和13在10（-8）和10（-6）M之间的有趣选择性。

  DOI：

  10.1016/j.farmac.2003.11.014
• 作为产物：
  描述：

  酮基丙二酸二乙酯 在 N,N-二甲基甲酰胺 、 柠檬酸 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 3-氯-6-(三氟甲基)喹喔啉-2-羧酸乙酯
  参考文献：
  名称：

  新的喹喔啉衍生物作为双重Pim-1 / 2激酶抑制剂：设计，合成和生物学评价。

  摘要：

  已在多种血液学（例如多发性骨髓瘤或急性骨髓性白血病（AML））和实体（例如结直肠癌）肿瘤中发现了莫洛尼氏鼠白血病病毒（Pim）-1/2激酶过表达的前病毒整合位点，在癌症进展，转移和耐药中起关键作用，并且与不良预后有关。因此，这些激酶被认为是肿瘤学中令人关注的靶标。我们在此报告了新的喹喔啉衍生物作为双重Pim1 / 2抑制剂的设计，合成，结构-活性关系（SAR）和体外评估。两种铅化合物（5c和5e然后确定）为有效的亚微摩尔Pim-1和Pim-2抑制剂。这些分子还能够抑制两种人类细胞系MV4-11（AML）和HCT-116（结肠直肠癌）的生长，并表达高内源性的Pim-1 / 2激酶。

  DOI：

  10.3390/molecules26040867

文献信息

• TRI-SUBSTITUTED PYRIMIDINE COMPOUNDS AND THEIR USE AS PDE10 INHIBITORS
  申请人：Kawanishi Eiji

  公开号：US20110160206A1

  公开（公告）日：2011-06-30

  The present invention provides a tri-substituted pyrimidine compound having an excellent PDE10 inhibitory activity. The present invention relates to a tri-substituted pyrimidine compound represented by the following formula [I 0 ] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compound for PDE10 inhibitor, and a pharmaceutical composition comprising said compounds as an active ingredient: wherein: either one of X 1 and X 2 is N, and the other of X 1 and X 2 is CH; A is *-CH═CH—, *-C(Alk)=CH—, *-CH 2 —CH 2 — or *-O—CH 2 — (* is a bond with R 1 ); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R 1 is an optionally substituted quinoxalinyl or an optionally substituted quinolyl; Y 0 is mono- or di-substituted amino group, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种具有优异的PDE10抑制活性的三取代嘧啶化合物。本发明涉及一种由以下式[I0]表示的三取代嘧啶化合物或其药学上可接受的盐，以及制备该化合物的方法，以及将所述化合物用作PDE10抑制剂的用途，以及包含所述化合物作为活性成分的药物组合物：其中：X1和X2中的任一者为N，另一者为CH；A为*-CH═CH—，*-C(Alk)=CH—，*-CH2—CH2—或*-O—CH2—（*是与R1形成键）；Alk为较低的烷基基团；环B为可选择地取代的含氮脂肪杂环基团；R1为可选择地取代的喹唑啉基或可选择地取代的喝啉基；Y0为单取代或双取代的氨基团，或其药学上可接受的盐。
• Quinoxaline chemistry
  作者：Gabriella Vitale、Paola Corona、Mario Loriga、Giuseppe Paglietti

  DOI：10.1016/s0014-827x(98)00075-5

  日期：1998.8

  Thirty quinoxalines bearing a substituted phenoxy or hydroxybenzoylglutamate group on position 2, a carboethoxy or carboxy group on position 3 and a trifluoromethyl group on position 6 or 7 of the heterocycle were prepared in order to evaluate the in vitro anticancer activity. Screening over 21 compounds selected at the National Cancer Institute (Bethesda, MD) showed that only few derivatives exhibited a moderate growth inhibition activity on various tumor panel cell lines at 10(-4) molar concentration. The acid derivatives showed no growth inhibition activity. The results obtained in this series seem to indicate that in general carboxy or carboethoxy groups close to O-link with phenyl or benzoyl glutamates on position 2 are detrimental for anticancer activity. (C) 1998 Elsevier Science S.A. All rights reserved.
• Quinoxaline chemistry. Part 13: 3-carboxy-2-benzylamino-substituted quinoxalines and N-[4-[(3-carboxyquinoxalin-2-yl) aminomethyl]benzoyl]-l-glutamates: synthesis and evaluation of in vitro anticancer activity
  作者：Paola Corona、Gabriella Vitale、Mario Loriga、Giuseppe Paglietti

  DOI：10.1016/s0014-827x(99)00119-6

  日期：2000.2

  Among a new series of 28 3-carboxy or carbethoxy quinoxalines bearing a substituted benzylamino or N-[4-(aminomethyl)benzoyl]glutamate group on position 2 of the ring and various substituents at C-6, 7 positions, 21 were selected at the National Cancer Institute for evaluation of their in vitro anticancer activity. The results obtained seem to confirm that the carboxy or carbethoxy group on position 3 is not helpful, with a few exceptions, for the anticancer activity. (C) 2000 Elsevier Science S.A. All rights reserved.
• Loriga; Piras; Sanna, Il Farmaco, 1997, vol. 52, # 3, p. 157 - 166
  作者：Loriga、Piras、Sanna、Paglietti

  DOI：——

  日期：——
• Quinoxaline chemistry. Part 14. 4-(2-Quinoxalylamino)-phenylacetates and 4-(2-quinoxalylamino)-phenylacetyl-l-glutamates as analogues–homologues of classical antifolate agents. Synthesis and evaluation of in vitro anticancer activity
  作者：Sandra Piras、Mario Loriga、Giuseppe Paglietti

  DOI：10.1016/s0014-827x(01)01159-4

  日期：2002.1

  Among a new series of 26 4-(3-substituted-2-quinoxalylamino)phenylacetates and 4-(3-substituted-2-quinoxalylamino)-phenylacetyl-L-glutamates, eight were selected at NO for evaluation of their in vitro anticancer activity. The results obtained in comparison with the corresponding nor-compounds series seem to indicate that this type of homologation is not helpful. (C) 2002 Elsevier Science S.A. All rights reserved.