2,4-dichloro-N,N-diethyl-1,8-naphthyridine-3-carboxamide | 126567-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2,4-dichloro-N,N-diethyl-1,8-naphthyridine-3-carboxamide
• 英文别名: 1,8-Naphthyridine-3-carboxamide, 2,4-dichloro-N,N-diethyl-
• CAS: 126567-71-3
• 化学式: C₁₃H₁₃Cl₂N₃O
• 分子量: 298.172
• InChiKey: XKMALZUOFIFIJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,4-dichloro-N,N-diethyl-1,8-naphthyridine-3-carboxamide 在 diphenyl ether-biphenyl eutectic 作用下， 以 乙二醇 为溶剂， 反应 24.33h， 生成 1-Isopropyl-5-phenylamino-2,3,9,9b-tetraaza-cyclopenta[a]naphthalene-4-carboxylic acid diethylamide
  参考文献：
  名称：

  1,8-Naphthyridines V. Novel N-substituted 5-amino-N,N-diethyl-9-isopropyl [1,2,4]triazolo[4,3-a] [1,8]naphthyridine-6-carboxamides, as potent anti-inflammatory and/or analgesic agents completely devoid of acute gastrolesivity

  摘要：

  Most N,N-disubstituted 5-amino-N,N-diethyl-9-isopropyl [1,2,4]triazolo[4,3-alpha] [1,8]naphthyridine-6-carboxamides 9 (compounds 9a, c-i) and the N-monosubstituted one 8c were obtained by treating with excess amine the corresponding 5-chloroderivative 7a, which was in turn prepared by cyclocondensation of the 2,4-dichloro-N,N-diethyl-1,8-naphthyridine-3-carboxamide (4a) with isobutyrohydrazide. Compounds 8a,b and 9b,j-m were obtained according with the methods shown in Scheme 1. The above now synthesized compounds, along with the previously described 8d and 8e, were tested for their anti-inflammatory, analgesic and antipyretic properties, and most compounds also for their effect on spontaneous mice locomotor activity and their acute gastrolesivity in rats. Several compounds showed potent anti-inflammatory and/or analgesic activities, and all the compounds tested proved to be completely lacking in acute gastrolesivity. In many cases compounds 8 and 9 produced hypothermic effect, usually at high doses. On the whole, the N-monosubstituted 5-aminoderivatives 8 appeared to be more potent anti-inflammatory agents than the corresponding N,N-disubstituted 9, whereas these latter compounds exhibited higher analgesic activity. (C) 2004 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.09.022
• 作为产物：
  描述：

  4-chloro-N,N-diethyl-1,2-dihydro-2-oxo-1,8-naphthyridine-3-carboxamide 在 三氯氧磷 作用下， 反应 0.5h， 以90.5%的产率得到2,4-dichloro-N,N-diethyl-1,8-naphthyridine-3-carboxamide
  参考文献：
  名称：

  Di Braccio; Roma; Balbi, Il Farmaco, 1989, vol. 44, # 9, p. 865 - 881

  摘要：

  DOI：

文献信息

• 1,8-Naphthyridines VI. Synthesis and anti-inflammatory activity of 5-(alkylamino)-N,N-diethyl[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides with a new substitution pattern on the triazole ring
  作者：Mario Di Braccio、Giancarlo Grossi、Giorgio Roma、Daniela Piras、Francesca Mattioli、Marzia Gosmar

  DOI：10.1016/j.ejmech.2007.04.016

  日期：2008.3

  in which the 9-alkyl substituent was replaced by an ester or amide group (compounds 3a-i), was prepared and tested (inhibition of carrageenan-induced paw edema in the rat). Also two 5-(N-alkyl,N-acylamino) derivatives (compounds 4a,b) were synthesized and evaluated for the same purpose. Even though the general trend for these new [1,2,4]triazolo[4,3-a][1,8]naphthyridine derivatives was a decrease

  基于9-烷基-N，N-二烷基-5-（烷基氨基）[1,2,4]三唑并[4,3-a] [1,8]萘啶-显示的良好的抗炎特性。制备并测试了6碳基乙酰胺1的一系列类似物，其中9-烷基取代基被酯或酰胺基取代（化合物3a-i）（抑制角叉菜胶诱发的爪水肿）。鼠）。还合成了两种5-（N-烷基，N-酰基氨基）衍生物（化合物4a，b），并出于相同目的对其进行了评估。尽管这些新的[1,2,4]三唑并[4,3-a] [1,8]萘啶衍生物的总体趋势是与化合物1相比活性降低，但一些新合成的化合物仍显示出良好的抗-发炎的特性。
• 1,8-Naphthyridines VIII. Novel 5-aminoimidazo[1,2-a] [1,8]naphthyridine-6-carboxamide and 5-amino[1,2,4]triazolo[4,3-a] [1,8]naphthyridine-6-carboxamide derivatives showing potent analgesic or anti-inflammatory activity, respectively, and completely devoid of acute gastrolesivity
  作者：Giorgio Roma、Mario Di Braccio、Giancarlo Grossi、Daniela Piras、Vigilio Ballabeni、Massimiliano Tognolini、Simona Bertoni、Elisabetta Barocelli

  DOI：10.1016/j.ejmech.2009.10.020

  日期：2010.1

  interesting pharmacological properties shown by the 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamide derivatives 1, previously described by us, we have now prepared the 5-aminoimidazo[1,2-a][1,8]naphthyridine-6-carboxamide derivatives 2a–o (a new structural class) whose tricyclic system is isosteric to that of compounds 1. Both compounds 2 and some new properly substituted compounds 1 (1f–k) now

  根据我们先前描述的5-氨基[1,2,4]三唑并[4,3- a ] [1,8]萘啶-6-羧酰胺衍生物1所显示的非常有趣的药理特性，我们有现在制备了5-氨基咪唑并[1,2- a ] [1,8]萘啶-6-羧酰胺衍生物2a - o（一种新的结构分类），其三环系统与化合物1的体系等排。化合物2和现在合成的一些新的适当取代的化合物1（1f - k）均已在体内进行了镇痛和抗炎活性测试：总体而言，化合物2具有明显的镇痛作用，而许多化合物1则显示出非常有效的抗炎活性，与稀少的镇痛活性相关。在大鼠中（200 mg kg -1口服剂量），所有有效化合物均被证明完全没有急性胃病（胃功能损害）。
• 1,8-Naphthyridines IX. Potent anti-inflammatory and/or analgesic activity of a new group of substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides, of some their Mannich base derivatives and of one novel substituted 5-amino-10-oxo-10H-pyrimido[1,2-a][1,8]naphthyridine-6-carboxamide derivative
  作者：Mario Di Braccio、Giancarlo Grossi、Silvana Alfei、Vigilio Ballabeni、Massimiliano Tognolini、Lisa Flammini、Carmine Giorgio、Simona Bertoni、Elisabetta Barocelli

  DOI：10.1016/j.ejmech.2014.08.069

  日期：2014.10

  A new group of 5-(alkylamino)-9-isopropyl[1,2,4]triazolo[4,3-a][1,8]naphthyridine derivatives bearing a CONHR group at the 6-position (1c-g), designed to obtain new effective analgesic and/or anti-inflammatory agents, were synthesized and tested along with three new 9-alkyl-5-(4-alkyl-1-piperazinyl)-N,N-diethyl [1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides (2b-d). Besides, a new class of analogues of compounds 1 and 2, bearing a Mannich base moiety at the 9-position (12a-d), as well as the novel N,N-diethyl-5-(isobutylamino)-8-methyl-10-oxo-10H-pyrimido[1,2-a][1,8]naphthyridine-6-carboxamide (15) were prepared and tested. Compounds 1c-g exhibited very interesting anti-inflammatory properties in rats, whereas compounds 2b-d and 15 proved to be endowed with prevalent analgesic activity frequently associated with sedative effects in mice. On the contrary, the Mannich bases 12a-d resulted inactive. The most effective (80% inhibition of oedema) and potent (threshold dose 1.6 mg kg(-1) with 31% inhibition of oedema) anti-inflammatory compound 1d did not show gastrolesive effects following 100 mg kg(-1) oral administration in rats. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 1,8-Naphthyridines VII. New substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides and their isosteric analogues, exhibiting notable anti-inflammatory and/or analgesic activities, but no acute gastrolesivity
  作者：Giorgio Roma、Giancarlo Grossi、Mario Di Braccio、Daniela Piras、Vigilio Ballabeni、Massimiliano Tognolini、Simona Bertoni、Elisabetta Barocelli

  DOI：10.1016/j.ejmech.2007.10.010

  日期：2008.8

  The [1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamide derivatives 5-amino (2) or 5-alkoxy (3) substituted and the 5-amino[1,2,4] triazolo[4,3-a]quinoline-4-carboxamide derivatives (4), designed to obtain new effective analgesic and/or anti-inflammatory agents were synthesized. Ten compounds 2 and 4 showed an interesting analgesic activity: the most potent ones are 2j (36% inhibition, P < 0.05) and 4b (77% inhibition, P < 0.01) at 6.25 and 25 mg kg(-1) doses, respectively. Compounds 2i-I and 4c showed notable anti-inflammatory properties: the most potent ones are 2i (68% inhibition, P < 0.01) and 21 (42% inhibition, P < 0.05) at 12.5 and 6.25 mg kg(-1) doses, respectively. The replacement in compounds 2 of the N-substituted 5-amino substituents with similar alkoxy groups usually afforded less active compounds 3. (c) 2007 Elsevier Masson SAS. All rights reserved.
• Di Braccio; Roma; Ghia, Il Farmaco, 1994, vol. 49, # 1, p. 25 - 32
  作者：Di Braccio、Roma、Ghia、Mattioli

  DOI：——

  日期：——