7-苄基-4-氯-5,6-二苯基-7H-吡咯并-[2,3-d]嘧啶 | 173458-82-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 7-苄基-4-氯-5,6-二苯基-7H-吡咯并-[2,3-d]嘧啶
• 英文名称: 7-benzyl-4-chloro-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 7-benzyl-4-chloro-5,6-diphenylpyrrolo[2,3-d]pyrimidine
• CAS: 173458-82-7
• 化学式: C₂₅H₁₈ClN₃
• 分子量: 395.891
• InChiKey: CLNNUPXMPYFDLW-UHFFFAOYSA-N

物化性质

• 熔点：
  190-192°C
• 沸点：
  581.1±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  7-苄基-4-氯-5,6-二苯基-7H-吡咯并-[2,3-d]嘧啶 在 硫脲 作用下， 以 乙醇 为溶剂， 反应 8.0h， 生成 2-(7-benzyl-5,6-diphenyl-3H-pyrrolo[2,3-d]pyrimidin-4-ylidene)malononitrile
  参考文献：
  名称：

  吡咯并嘧啶类新型螺衍生物作为抗高血糖化合物的合成和评价。

  摘要：

  Pyrrolopyrimidin-4-ylidene-malononitriles IIa-d were prepared as important intermediates for preparation of a new series of spiro-pyrrolopyrimidines. These intermediates undergo cyclisation via reaction with acetylacetone, guanidine hydrochloride or hydrazine hydrate. Elemental and spectroscopic evidences for the structures of these compounds are presented. The final compounds have been monitored for in vivo antihyperglycemic activity, compared with Amaryl as standard drug. Among 12 tested compounds, both spiro (pyrano IIIb and pyrazlo Va) derivatives exhibit promising anti-hyperglycemic activity.

  DOI：

  10.1080/14756366.2018.1461854
• 作为产物：
  描述：

  2-氨基-1-苄基-4,5-二苯基-1H-吡咯-3-甲腈 在 三氯氧磷 作用下， 生成 7-苄基-4-氯-5,6-二苯基-7H-吡咯并-[2,3-d]嘧啶
  参考文献：
  名称：

  四氢嘧啶-2-硫酮和吡咯衍生物作为肺炎克雷伯菌和铜绿假单胞菌金属β-内酰胺酶抑制剂的合成和动力学测试

  摘要：

  越来越多的细菌病原体产生的金属β-内酰胺酶（MBL）促进了许多常用的β-内酰胺抗生素的水解。没有针对MBL的临床上有用的拮抗剂。合成了两组四氢嘧啶-2-硫酮和吡咯衍生物，并分析了它们对铜绿假单胞菌和肺炎克雷伯菌的IMP-1 MBL催化活性的抑制作用。测试的9种化合物（1a，3b，5c，6b，7a，8a，11c，13a和16a）显示出微摩尔抑制常数（K我值的范围从~20-80μ米）。化合物1c，2b和15a仅显示弱抑制作用。在计算机芯片上的对接来探讨的最强抑制剂的每种对映体的结合模式，5C（ķ我 = 19±9μ米），以及图7a（ķ我 = 21±10μ米），的最强抑制剂吡咯系列，在IMP-1的活动站点中。

  DOI：

  10.1111/j.1747-0285.2012.01440.x

文献信息

• Identification, SAR Studies, and X-ray Co-crystallographic Analysis of a Novel Furanopyrimidine Aurora Kinase A Inhibitor
  作者：Mohane Selvaraj Coumar、Ming-Tsung Tsai、Chang-Ying Chu、Biing-Jiun Uang、Wen-Hsing Lin、Chun-Yu Chang、Teng-Yuan Chang、Jiun-Shyang Leou、Chi-Huang Teng、Jian-Sung Wu、Ming-Yu Fang、Chun-Hwa Chen、John T.-A. Hsu、Su-Ying Wu、Yu-Sheng Chao、Hsing-Pang Hsieh

  DOI：10.1002/cmdc.200900339

  日期：2010.2.1

  simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in‐house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in‐house compound library collection prior to testing. Five

  本文中，我们揭示了一种通过内部化合物库的亚结构搜索来鉴定新的Aurora激酶A抑制剂的简单方法，以选择要测试的化合物。赋予Aurora激酶活性的片段和激酶抑制剂中最常报告的杂环用作子结构查询，以在测试前过滤内部化合物库的馆藏。五个新的系列的极光激酶抑制剂是通过这种策略识别与IC 50个值范围为约300Ñ中号至〜15μ中号，通过从~125 000化合物数据库仅测试133的化合物。最有效的化合物呋喃并嘧啶衍生物与IC的结构活性关系研究和X射线共晶体分析50的309的n值中号朝向极光激酶A，进行了。通过这些研究获得的知识可能有助于将来设计有效的Aurora激酶抑制剂。
• Synthesis and Kinetic Testing of Tetrahydropyrimidine-2-thione and Pyrrole Derivatives as Inhibitors of the Metallo-β-lactamase from<i>Klebsiella pneumonia</i>and<i>Pseudomonas aeruginosa</i>
  作者：Waleed M. Hussein、Samar S. Fatahala、Zainab M. Mohamed、Ross P. McGeary、Gerhard Schenk、David L. Ollis、Mosaad S. Mohamed

  DOI：10.1111/j.1747-0285.2012.01440.x

  日期：2012.10

  5c, 6b, 7a, 8a, 11c, 13a, and 16a) showed micromolar inhibition constants (Ki values range from ∼20–80 μm). Compounds 1c, 2b, and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (Ki = 19 ± 9 μm), as well as 7a (Ki = 21 ± 10 μm), the strongest inhibitor of the pyrrole series, in the active site of IMP‐1.

  越来越多的细菌病原体产生的金属β-内酰胺酶（MBL）促进了许多常用的β-内酰胺抗生素的水解。没有针对MBL的临床上有用的拮抗剂。合成了两组四氢嘧啶-2-硫酮和吡咯衍生物，并分析了它们对铜绿假单胞菌和肺炎克雷伯菌的IMP-1 MBL催化活性的抑制作用。测试的9种化合物（1a，3b，5c，6b，7a，8a，11c，13a和16a）显示出微摩尔抑制常数（K我值的范围从~20-80μ米）。化合物1c，2b和15a仅显示弱抑制作用。在计算机芯片上的对接来探讨的最强抑制剂的每种对映体的结合模式，5C（ķ我 = 19±9μ米），以及图7a（ķ我 = 21±10μ米），的最强抑制剂吡咯系列，在IMP-1的活动站点中。
• Synthesis and Biological Evaluation of Some Pyrrolo[2,3-d]pyrimidines
  作者：Aymn E. Rashad、Mosaad S. Mohamed、Magdy E. A. Zaki、Samar S. Fatahala

  DOI：10.1002/ardp.200600055

  日期：2006.12

  Pyrrolo[2,3‐d]pyrimidine and tetrazolopyrimidine derivatives 2a, b–5a, b were prepared. Also, acyclic and cyclic C‐nucleosides 7a, b–12a, b were prepared by treating compound 6 with some aldoses. All prepared products were tested for antiviral activity against hepatitis‐A virus (HAV, MBB‐cell culture adapted strain) and herpes simplex virus type‐1 (HSV‐1). Plaque reduction infectivity assay was used

  制备了吡咯并[2,3-d]嘧啶和四唑并嘧啶衍生物2a、b-5a、b。此外，通过用一些醛糖处理化合物 6 制备了无环和环状 C-核苷 7a、b-12a、b。测试所有制备的产品对甲型肝炎病毒（HAV，MBB 细胞培养适应株）和单纯疱疹病毒 1 型（HSV-1）的抗病毒活性。噬斑减少感染性测定用于确定由于用测试化合物处理而导致的病毒计数减少。化合物 2a 对 HAV 的作用最高，而化合物 11b 对 HSV-1 病毒的作用最高。
• Structure-Based Design of Novel Chk1 Inhibitors:  Insights into Hydrogen Bonding and Protein−Ligand Affinity
  作者：Nicolas Foloppe、Lisa M. Fisher、Rob Howes、Peter Kierstan、Andrew Potter、Alan G. S. Robertson、Allan E. Surgenor

  DOI：10.1021/jm049022c

  日期：2005.6.1

  We report the discovery, synthesis, and crystallographic binding mode of novel furanopyrimidine and pyrrolopyrimidine inhibitors of the Chk1 kinase, an oncology target. These inhibitors are synthetically tractable and inhibit Chk1 by competing for its ATP site. A chronological account allows an objective comparison of modeled compound docking modes to the subsequently obtained crystal structures. The comparison provides insights regarding the interpretation of modeling results, in relationship to the multiple reasonable docking modes which may be obtained in a kinase-ATP site. The crystal structures were used to guide medicinal chemistry efforts. This led to a thorough characterization of a pair of ligand-protein complexes which differ by a single hydrogen bond. An analysis indicates that this hydrogen bond is expected to contribute a fraction of the 10-fold change in binding affinity, adding a valuable observation to the debate about the energetic role of hydrogen bonding in molecular recognition.
• 4-(Phenylamino)pyrrolopyrimidines:  Potent and Selective, ATP Site Directed Inhibitors of the EGF-Receptor Protein Tyrosine Kinase
  作者：Peter M. Traxler、Pascal Furet、Helmut Mett、Elisabeth Buchdunger、Thomas Meyer、Nicholas Lydon

  DOI：10.1021/jm960118j

  日期：1996.1.1

  Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of the EGF-R protein tyro sine kinase (PTK), 4(phenylamino)-7H-pyrrolo[2,3-d]pyrimidines have been identified as a novel class of potent EGF-R protein tyrosine kinase inhibitors. In an interactive process, this class of compounds was then optimized. 13, 14, 28, 36, 37, and 44, the most potent compounds of this series, inhibited the EGF-R PTK with IC50 values in the low nanomolar range. High selectivity toward a panel of nonreceptor tyrosine kinases (c-Src, v-Abl) and serine/threonine kinases (PKC alpha, PKA) was observed. Kinetic analysis revealed competitive type kinetics relative to ATP. In cells, EGF-stimulated cellular tyrosine phosphorylation was inhibited by compounds 13, 36, 37, and 44 at IC50 values between 0.1 and 0.4 mu M, whereas PDGF-induced tyrosine phosphorylation was not affected by concentrations up to 10 M. In addition, these compounds were able to selectively inhibit c-fos mRNA expression in EGF-dependent cell lines with IC50 values between 0.1 and 2 mu M, but did not affect c-fos mRNA induction in response to PDGF or PMA (IC50 > 100 mu M) Proliferation of the EGF-dependent MK cell line was inhibited with similar IC50 values. From SAR studies, a binding mode for 4-(phenylamino)-7H-pyrrolo [2,3-d]pyrimidines as well as for the structurally related 4-(phenylamino)quinazolines at the ATP-binding site of the EGF-R tyrosine kinase is proposed. 4-(Phenylamino)-7H-pyrrolo [2,3-d]pyrimidines therefore represent a new class of highly potent tyrosine kinase inhibitors which preferentially inhibit the EGF-mediated signal transduction pathway and, ha ire the potential for further evaluation as anticancer agents.