7-benzyl-5,6-diphenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one | 173458-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 7-benzyl-5,6-diphenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
• 英文别名: 7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol；7-benzyl-5,6-diphenyl-3H-pyrrolo[2,3-d]pyrimidin-4-one
• CAS: 173458-79-2
• 化学式: C₂₅H₁₉N₃O
• 分子量: 377.445
• InChiKey: YAVXBOZEZAKCCF-UHFFFAOYSA-N

物化性质

• 熔点：
  220-222 °C(Solv: ethanol (64-17-5))
• 沸点：
  611.2±55.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 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：
  46.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-benzyl-5,6-diphenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 在 三氯氧磷 作用下， 反应 3.0h， 以46%的产率得到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：

  新型呋喃嘧啶极光激酶A抑制剂的鉴定，SAR研究和X射线共晶体分析

  摘要：

  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。

  DOI：

  10.1002/cmdc.200900339
• 作为产物：
  描述：

  甲酸 、 2-氨基-1-苄基-4,5-二苯基-1H-吡咯-3-甲腈 反应 6.0h， 以62%的产率得到7-benzyl-5,6-diphenyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  新型呋喃嘧啶极光激酶A抑制剂的鉴定，SAR研究和X射线共晶体分析

  摘要：

  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。

  DOI：

  10.1002/cmdc.200900339

文献信息

• 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。
• Pyrrolopyrimidine derivatives having pharmacological activity
  申请人：Novartis Corporation

  公开号：US05686457A1

  公开（公告）日：1997-11-11

  The invention relates to the use of the compounds mentioned below in the therapeutic treatment of tumour diseases and other proliferative diseases, such as psoriasis, and to novel compounds of that type. The compounds are compounds of formula I ##STR1## wherein n is from 0 to 5 and, when n is not 0, R is one or more substituents selected from halogen, alkyl, trifluoromethyl and alkoxy; and R.sub.1 and R.sub.2 are each independently of the other alkyl, or phenyl that is unsubstituted or substituted by halogen, trifluoromethyl, alkyl or by alkoxy, it also being possible for one of the two radicals R.sub.1 and R.sub.2 to be hydrogen, or R.sub.1 and R.sub.2 together form an alkylene chain having from 2 to 5 carbon atoms that is unsubstituted or substituted by alkyl; or salts thereof. Compounds of formula I inhibit protein kinases, for example the tyrosine protein kinase of the receptor for the epidermal growth factor, EGF.

  该发明涉及以下化合物在治疗肿瘤疾病和其他增生性疾病（如牛皮癣）中的使用，以及该类新化合物。这些化合物是具有以下结构的化合物：其中n为0至5，当n不为0时，R是来自卤素、烷基、三氟甲基和烷氧基中的一个或多个取代基；R1和R2各自独立于另一个是烷基或苯基，该苯基未取代或被卤素、三氟甲基、烷基或烷氧基取代，也可能是两个基团R1和R2中的一个是氢，或者R1和R2一起形成一个具有2至5个碳原子的烷基链，该链未取代或被烷基取代；或其盐。具有该结构的化合物抑制蛋白激酶，例如表皮生长因子受体的酪氨酸蛋白激酶。
• Davoodnia; Bakavoli; Khashi, Asian Journal of Chemistry, 2010, vol. 22, # 6, p. 4625 - 4628
  作者：Davoodnia、Bakavoli、Khashi、Moloudi、Tavakoli-Hoseini

  DOI：——

  日期：——
• 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.
• Synthesis and evaluation of novel spiro derivatives for pyrrolopyrimidines as anti-hyperglycemia promising compounds
  作者：Samar Said Fatahala、Shahenda Mahgub、Heba Taha、Rania Helmy Abd-El Hameed

  DOI：10.1080/14756366.2018.1461854

  日期：2018.1.1

  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.