4-(m-chloroanilino)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine | 173458-67-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-(m-chloroanilino)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: N-(3-Chlorophenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine-4-amine；N-(3-chlorophenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine
• CAS: 173458-67-8
• 化学式: C₂₄H₁₇ClN₄
• 分子量: 396.879
• InChiKey: UYXXIXVMSUKWBN-UHFFFAOYSA-N

物化性质

• 沸点：
  566.6±60.0 °C(Predicted)
• 密度：
  1.30±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：
  0.0
• 拓扑面积：
  53.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氨基-1-苄基-4,5-二苯基-1H-吡咯-3-甲腈 在 三氯化铝 、 三氯氧磷 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 26.5h， 生成 4-(m-chloroanilino)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidine
  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

文献信息

• Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
  申请人：Novartis AG

  公开号：EP0682027B1

  公开（公告）日：1997-10-15
• PYRROLOPYRIMIDINES FOR PHARMACEUTICAL COMPOSITIONS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2041137B1

  公开（公告）日：2011-09-28
• US6096749A
  申请人：——

  公开号：US6096749A

  公开（公告）日：2000-08-01
• [EN] MODULATORS OF THE EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) PATHWAY FOR USE IN THE TREATMENT OR PREVENTION OF SUBSTANCE ABUSE<br/>[FR] MODULATEURS DE LA VOIE DES RÉCEPTEURS DU FACTEUR DE CROISSANCE ÉPIDERMIQUE (EGFR) POUR UTILISATION DANS LE TRAITEMENT OU LA PRÉVENTION DE LA CONSOMMATION EXCESSIVE D'ALCOOL OU D'AUTRES DROGUES
  申请人：UNIV CALIFORNIA

  公开号：WO2009070328A1

  公开（公告）日：2009-06-04

  The present invention provides methods of using modulators of the epidermal growth factor receptor (EGFR) pathway for treatment or prevention of substance abuse such as alcohol abuse. The modulators include small molecule inhibitors such as Erlotinib (TARCEVA®, N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4- quinazolineamine) or a pharmaceutically acceptable salt, hydrate or prodrug thereof and Gefitinib [IRES S A®, N-(3 -chloro-4-fluoro-phenyl)-7-methoxy-6-(3 -morpholin-4- ylpropoxy)quinazolin-4-amine] or a pharmaceutically acceptable salt, hydrate or prodrug thereof and various macromolecular inhibitors of the EGFR pathway such as siRNAs and antibodies that target genes or proteins in the EGFR/ERK pathway such as one of the EGFR/ErbB protein or a homolog thereof.
• 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.