7-benzyl-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol | 173458-77-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 7-benzyl-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol
• 英文别名: 4-hydroxy-5,6-dimethyl-7-benzyl-pyrrolo[2,3-d]pyrimidine；7-benzyl-5,6-dimethyl-3H-pyrrolo[2,3-d]pyrimidin-4-one
• CAS: 173458-77-0
• 化学式: C₁₅H₁₅N₃O
• 分子量: 253.304
• InChiKey: CZWRTMRQPGTVBF-UHFFFAOYSA-N

物化性质

• 沸点：
  511.2±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)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 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-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol 在 三氯化铝 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 4.5h， 生成 4-氯-5,6-二甲基-7h-吡咯并[2,3-d]嘧啶
  参考文献：
  名称：

  4-(Phenylamino)pyrrolopyrimidines:  Potent and Selective, ATP Site Directed Inhibitors of the EGF-Receptor Protein Tyrosine Kinase

  摘要：

  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.

  DOI：

  10.1021/jm960118j
• 作为产物：
  描述：

  苄胺 在 盐酸 作用下， 以 甲苯 为溶剂， 反应 31.0h， 生成 7-benzyl-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol
  参考文献：
  名称：

  白介素1受体相关激酶4（IRAK4）的吡咯并嘧啶抑制剂的发现和优化，用于治疗突变型MYD88 L265P弥漫性大B细胞淋巴瘤。

  摘要：

  本文中，我们报告了使用X射线晶体结构和基于结构的设计来鉴定和优化我们的支架，优化了一系列白介素1受体相关激酶4（IRAK4）的吡咯并嘧啶抑制剂。化合物28表现出良好的理化和激酶选择性，并被认为是一种有前途的体内工具，可利用该工具探索IRAK4抑制作用在突变MYD88 L265P弥漫性大B细胞淋巴瘤（DLBCL）的治疗中的作用。化合物28已显示在体​​外高浓度下具有抑制NF-κB活化和ABC亚型ABC亚型生长的能力，但与低浓度下的BTK抑制剂联用则显示出更大的作用。在体内，化合物28和依鲁替尼的组合在ABC-DLBCL小鼠模型中导致肿瘤消退。

  DOI：

  10.1021/acs.jmedchem.7b01290

文献信息

• 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。
• SUBSTITUTED PYRROLO[2,3-d]PYRIMIDINES FOR THE TREATMENT OF CANCER AND PROLIFERATIVE DISORDERS
  申请人：Northwestern University

  公开号：US20160002252A1

  公开（公告）日：2016-01-07

  Disclosed are substituted pyrrolo[2,3-d]pyrimidine compounds. The disclosed compounds are shown to be useful in inhibiting the growth of cancer cell lines and treating cancer and cell proliferative disorders.

  公开了取代的吡咯并[2,3-d]嘧啶化合物。所公开的化合物被证明在抑制癌细胞系的生长和治疗癌症和细胞增殖性疾病方面是有用的。
• Pyrrolopyrimidines for pharmaceutical compositions
  申请人：DeveloGen Aktiengesellschaft

  公开号：EP1889847A1

  公开（公告）日：2008-02-20

  The present invention relates to novel pyrrolopyrimidine compounds of the general formula (1) and pharmaceutical compositions comprising said pyrrolopyrimidine compounds. Moreover, the present invention relates to the use of the pyrrolopyrimidine compounds of the invention for the production of pharmaceutical compositions for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.

  本发明涉及通式（1）的新型吡咯并嘧啶化合物 以及包含所述吡咯并嘧啶化合物的药物组合物。此外，本发明还涉及使用本发明的吡咯并嘧啶化合物生产药物组合物，用于预防和/或治疗可受 Mnk1 和/或 Mnk2（Mnk2a 或 Mnk2b）和/或其变体的激酶活性抑制影响的疾病。
• Rapid and Efficient, Microwave-Assisted, Base-Catalyzed Synthesis of Some Novel 2,7-Disubstituted Pyrrolopyrimidinones
  作者：Murty Deverakonda、Raghu Prasad Mailavaram、Pran Kishore Deb、Narsaiah Banda、Girija Sastry Vedula

  DOI：10.1080/00397911.2011.576324

  日期：2012.11

  A rapid synthesis of a series of new 5,6-dimethyl-7-phenyl-2-alkyl-3,7-dihydro-4-H-pyrrolo[2,3-d]pyrimidinones and 5,6-dimethyl-7-benzyl-2-alkyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidinones was accomplished in good yields using microwave irradiation under base catalysis.
• WO2008/6547
  申请人：——

  公开号：——

  公开（公告）日：——