5,6,7,8-四氢-2-苯基-6-(苯基甲基)-吡啶并[4,3-d]嘧啶-4(3h)-酮 | 1047-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 5,6,7,8-四氢-2-苯基-6-(苯基甲基)-吡啶并[4,3-d]嘧啶-4(3h)-酮
• 英文名称: 6-benzyl-2-phenyl-5,6,7,8-tetrahydro-3H-pyrido<4,3-d>pyrimidin-4-one
• 英文别名: 6-benzyl-2-phenyl-3,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidin-4-one；6-Benzyl-2-phenyl-5,6,7,8-tetrahydro-3H-pyrido[4,3-d]pyrimidin-4-one；6-benzyl-2-phenyl-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one
• CAS: 1047-48-9
• 化学式: C₂₀H₁₉N₃O
• mdl: MFCD06779866
• 分子量: 317.39
• InChiKey: DDSHIPPHMFBBSN-UHFFFAOYSA-N

物化性质

• 熔点：
  245 °C
• 沸点：
  491.5±55.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  44.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5,6,7,8-四氢-2-苯基-6-(苯基甲基)-吡啶并[4,3-d]嘧啶-4(3h)-酮 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 24.0h， 生成 6-[(1R,2R)-2-hydroxycyclohexyl]-2-phenyl-1,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one
  参考文献：
  名称：

  饱和杂环，第172部分†。2,6-二取代的5,6,7,8-四氢吡啶并[4,3- d ]嘧啶衍生物的合成

  摘要：

  通过将丙烯酸甲酯添加到苄胺或α-氨基吡啶上，合成标题化合物，得到相应的二酯，例如。12，然后由后者进行Dieckmann缩合，得到酮酯13，将其与am和胍3，14缩合。通过氢解除去苄基并随后将所得化合物5中6位的氮原子烷基化，同时改变C-2上的取代基，得到了许多具有潜在生物学作用的产物；其中一些具有止痛和抗炎作用。

  DOI：

  10.1002/jhet.5570270708
• 作为产物：
  描述：

  苄胺 在 sodium methylate 、 sodium ethanolate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 15.0h， 生成 5,6,7,8-四氢-2-苯基-6-(苯基甲基)-吡啶并[4,3-d]嘧啶-4(3h)-酮
  参考文献：
  名称：

  饱和杂环，第172部分†。2,6-二取代的5,6,7,8-四氢吡啶并[4,3- d ]嘧啶衍生物的合成

  摘要：

  通过将丙烯酸甲酯添加到苄胺或α-氨基吡啶上，合成标题化合物，得到相应的二酯，例如。12，然后由后者进行Dieckmann缩合，得到酮酯13，将其与am和胍3，14缩合。通过氢解除去苄基并随后将所得化合物5中6位的氮原子烷基化，同时改变C-2上的取代基，得到了许多具有潜在生物学作用的产物；其中一些具有止痛和抗炎作用。

  DOI：

  10.1002/jhet.5570270708

文献信息

• Tetrahydropyridine (THP) ring expansion under the action of activated terminal alkynes. The first synthesis and X-ray crystal structure of tetrahydropyrimido[4,5-d]azocines
  作者：Leonid G. Voskressensky、Tatiana N. Borisova、Innokenti S. Kostenev、Larisa N. Kulikova、Alexey V. Varlamov

  DOI：10.1016/j.tetlet.2005.11.136

  日期：2006.2

  Tetrahydropyridopyrimidines (THPPm) 1–3 underwent tandem cleavage–cyclization piperidine ring enlargement under the action of terminal activated alkynes to produce tetrahydropyrimido[4,5-d]azocines 4–7 in good preparative yields. The latter compounds are representatives of a new heterocyclic system.

  Tetrahydropyridopyrimidines（THPPm）1 - 3后行串联切割环化终端而激活炔以产生四氢嘧啶并[4,5-的作用下哌啶环放大d ] azocines 4 - 7中制备好的产率。后一种化合物是新杂环系统的代表。
• Transformations of tetrahydrobenzo[b][1,6]naphthyridines and tetrahydropyrido[4,3-b]pyrimidines under the action of dimethyl acetylene dicarboxylate
  作者：Leonid G. Voskressensky、Tatiana N. Borisova、Innokenti S. Kostenev、Ilia V. Vorobiev、Alexey V. Varlamov

  DOI：10.1016/j.tetlet.2005.02.001

  日期：2005.3

  6]naphthyridines 3, 4 undergo addition of DMAD, followed by a Stevens rearrangement of the intermediate ylide to yield methyl dioates 8 and 9. An alternative transformation sequence starts with migration of the dimethyl butenedioate anion to the carbon of the CN group, followed by the addition of 1 mol of water, to provide succinates 10 and 11. In contrast, tetrahydropyrido[4,3-b]pyrimidines 5–7 undergo a tandem

  10 Cyanotetrahydrobenzo [ b ] [1,6]萘啶3，4进行加成DMAD，随后通过中间叶立德的史蒂文斯重排，得到甲基dioates 8和9。替代的转化顺序以丁烯二酸二甲酯的阴离子向CN基团的碳迁移开始，然后加入1摩尔水，以生成琥珀酸酯10和11。相反，四氢吡啶并[4,3- b ]嘧啶5 – 7经历一分子溶剂的串联裂解过程。生成的烯胺很容易被强酸裂解，得到二氢嘧啶基乙胺，而该胺几乎不能通过其他合成方法获得。
• QUINAZOLINE DERIVATIVES AS MEDICAMENTS
  申请人：DUGAR Sundeep

  公开号：US20070293500A1

  公开（公告）日：2007-12-20

  Quinazoline derivatives and their pharmaceutically acceptable salts are inhibitors of TGFβ activity and are used to treat conditions characterized by enhanced TGFβ activity.

  喹唑啉衍生物及其药学上可接受的盐是TGFβ活性的抑制剂，用于治疗TGFβ活性增强的疾病。
• Structure-based design, synthesis and evaluation in vitro of arylnaphthyridinones, arylpyridopyrimidinones and their tetrahydro derivatives as inhibitors of the tankyrases
  作者：Katerina Kumpan、Amit Nathubhai、Chenlu Zhang、Pauline J. Wood、Matthew D. Lloyd、Andrew S. Thompson、Teemu Haikarainen、Lari Lehtiö、Michael D. Threadgill

  DOI：10.1016/j.bmc.2015.05.005

  日期：2015.7

  The tankyrases are members of the PARP superfamily; they poly(ADP-ribosyl) ate their target proteins using NAD(+) as a source of electrophilic ADP-ribosyl units. The three principal protein substrates of the tankyrases (TRF1, NuMA and axin) are involved in replication of cancer cells; thus inhibitors of the tankyrases may have anticancer activity. Using structure-based drug design and by analogy with known 3-arylisoquinolin-1-one and 2-arylquinazolin-4-one inhibitors, series of arylnaphthyridinones, arylpyridinopyrimidinones and their tetrahydro-derivatives were synthesised and evaluated in vitro. 7-Aryl-1,6-naphthyridin-5-ones, 3-aryl-2,6-naphthyridin-1-ones and 3-aryl-2,7-naphthyridin-1-ones were prepared by acid-catalysed cyclisation of the corresponding arylethynylpyridinenitriles or reaction of bromopyridinecarboxylic acids with beta-diketones, followed by treatment with NH3. The 7-aryl-1,6-naphthyridin-5-ones were methylated at 1-N and reduced to 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones. Cu-catalysed reaction of benzamidines with bromopyridinecarboxylic acids furnished 2-arylpyrido[2,3-d]pyrimidin-4-ones. Condensation of benzamidines with methyl 1-benzyl-4-oxopiperidine-3-carboxylate and deprotection gave 2-aryl-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidin-4-ones, aza analogues of the known inhibitor XAV939. Introduction of the ring-N in the arylnaphthyridinones and the arylpyridopyrimidinones caused > 1000-fold loss in activity, compared with their carbocyclic isoquinolinone and quinazolinone analogues. However, the 7-aryl-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-ones showed excellent inhibition of the tankyrases, with some examples having IC50 = 2 nM. One compound (7-(4-bromophenyl)-1-methyl-1,2,3,4-tetrahydro-1,6-naphthyridin-5-one) showed 70-fold selectivity for inhibition of tankyrase-2 versus tankyrase-1. The mode of binding was explored through crystal structures of inhibitors in complex with tankyrase-2. (C) 2015 Elsevier Ltd. All rights reserved.
• Huber, Imre; Fueloep, Ferenc; Lazar, Janos, Journal of the Chemical Society. Perkin transactions I, 1992, # 1, p. 157 - 162
  作者：Huber, Imre、Fueloep, Ferenc、Lazar, Janos、Bernath, Gabor、Toth, Gabor

  DOI：——

  日期：——