4-hydroxy-5,6-tetramethylene-7-benzyl-pyrrolo[2,3-d]pyrimidine | 173458-78-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-hydroxy-5,6-tetramethylene-7-benzyl-pyrrolo[2,3-d]pyrimidine
• 英文别名: 3,5,6,7,8,9-Hexahydro-9-(phenylmethyl)-4H-pyrimido[4,5-b]indol-4-one；9-benzyl-5,6,7,8-tetrahydro-3H-pyrimido[4,5-b]indol-4-one
• CAS: 173458-78-1
• 化学式: C₁₇H₁₇N₃O
• 分子量: 279.341
• InChiKey: YRNFITOMSXLUBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  4-hydroxy-5,6-tetramethylene-7-benzyl-pyrrolo[2,3-d]pyrimidine 在 三氯化铝 、 三氯氧磷 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 21.5h， 生成 3-(6,7,8,9-Tetrahydro-5H-pyrimido[4,5-b]indol-4-ylamino)-benzoic acid
  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：

  甲酸 、 2-amino-1-benzyl-4,5,6,7-tetrahydro-1H-indole-3-carbonitrile 反应 5.0h， 生成 4-hydroxy-5,6-tetramethylene-7-benzyl-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

• 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。
• Pyrrolopyrimidinderivate mit antiproliferativer Wirkung
  申请人：Novartis AG

  公开号：EP0682027B1

  公开（公告）日：1997-10-15
• US6096749A
  申请人：——

  公开号：US6096749A

  公开（公告）日：2000-08-01
• US6140332A
  申请人：——

  公开号：US6140332A

  公开（公告）日：2000-10-31