4-(M-氯苯胺)-5,6-二甲基-7h-吡咯并[2,3-d]嘧啶 | 173458-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 中文名称: 4-(M-氯苯胺)-5,6-二甲基-7h-吡咯并[2,3-d]嘧啶
• 英文名称: 4-(3-chlorophenylamino)-5,6-dimethyl-7H-pyrrolo-[2,3-d]pyrimidine
• 英文别名: CGP 59326；CGP59326；4-(m-chloroanilino)-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidine；CGP-59326；4-(3-Chlorophenylamino)-5,6-dimethyl-7H-pyrrolo(2,3-d)pyrimidine；N-(3-chlorophenyl)-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine
• CAS: 173458-56-5
• 化学式: C₁₄H₁₃ClN₄
• 分子量: 272.737
• InChiKey: WXJDWBDGDSXEFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  53.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 4-(M-氯苯胺)-5,6-二甲基-7h-吡咯并[2,3-d]嘧啶 以 乙醇 为溶剂， 反应 0.75h， 以90%的产率得到4-(3-chlorophenylamino)-5,6-dimethyl-7H-pyrrolo-[2,3-d]pyrimidine methylsulfonic acid salt
  参考文献：
  名称：

  通过 Dakin-West 反应和 Dimroth 重排大规模合成吡咯并[2,3-d]嘧啶

  摘要：

  吡咯并[2,3-d]嘧啶作为药物活性化合物已被广泛研究。在本文中，我们提出了一种从廉价丙氨酸和丙二腈开始的 4-(3-氯苯基氨基)-5,6-二甲基-7H-吡咯并[2,3-d]嘧啶的短而有效的合成方法。据我们所知，Dakin-West 反应在工厂规模上的首次应用是通过精心设计避免二氧化碳不受控制释放的改进程序来证明的。嘧啶环的形成是在简单的一锅反应中实现的，然后是同样简单的异构化反应。整个合成过程既不需要色谱，也不需要萃取，不需要废物处理，也不需要特殊设备，是一个非常生态和经济的过程。

  DOI：

  10.1021/op010041v
• 作为产物：
  描述：

  N,N'-二-(3-氯苯基)甲脒 以 乙醇 、 水 、 乙二醇 为溶剂， 反应 22.0h， 生成 4-(M-氯苯胺)-5,6-二甲基-7h-吡咯并[2,3-d]嘧啶
  参考文献：
  名称：

  通过 Dakin-West 反应和 Dimroth 重排大规模合成吡咯并[2,3-d]嘧啶

  摘要：

  吡咯并[2,3-d]嘧啶作为药物活性化合物已被广泛研究。在本文中，我们提出了一种从廉价丙氨酸和丙二腈开始的 4-(3-氯苯基氨基)-5,6-二甲基-7H-吡咯并[2,3-d]嘧啶的短而有效的合成方法。据我们所知，Dakin-West 反应在工厂规模上的首次应用是通过精心设计避免二氧化碳不受控制释放的改进程序来证明的。嘧啶环的形成是在简单的一锅反应中实现的，然后是同样简单的异构化反应。整个合成过程既不需要色谱，也不需要萃取，不需要废物处理，也不需要特殊设备，是一个非常生态和经济的过程。

  DOI：

  10.1021/op010041v

文献信息

• Broad Spectrum Chemistry as Practised by Novartis Process Research
  作者：Stuart J. Mickel、Reto Fischer、Wolfgang Marterer

  DOI：10.2533/000942904777677533

  日期：——

  Three actual examples from the current product palette within Novartis Process Research will demonstrate the some of the variety and challenges encountered in modern chemical development.

  三个来自诺华过程研究当前产品系列的实际例子将展示现代化学开发中遇到的一些多样性和挑战。
• 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.

  本发明涉及以下化合物在治疗肿瘤疾病和其他增殖性疾病（如牛皮癣）中的使用，以及该类型的新化合物。该化合物是式I的化合物 其中n为0至5，当n不为0时，R是卤素，烷基，三氟甲基和烷氧基中的一个或多个取代基；R1和R2各自独立地为烷基或苯基，该苯基未取代或通过卤素，三氟甲基，烷基或烷氧基取代，也可以R1和R2中的一个为氢，或R1和R2共同形成一个有2至5个碳原子的烷基链，该链未取代或通过烷基取代；或其盐。式I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EGF。
• Three hybrid assay system
  申请人：GPC Biotech AG

  公开号：EP1975620A2

  公开（公告）日：2008-10-01

  The invention provides compositions and methods for isolating ligand binding polypeptides for a user-specified ligand, and for isolating small molecule ligands for a user-specified target polypeptide using an improved class of hypbrid ligand compounds.

  本发明提供了用于分离用户指定配体的配体结合多肽的组合物和方法，以及使用改良的低杂合配体化合物分离用户指定目标多肽的小分子配体的组合物和方法。
• Dynamic superparamagnetic markers
  申请人：——

  公开号：US20030201208A1

  公开（公告）日：2003-10-30

  The invention relates to the use of dynamic magnetic fields (DM fields) or DM-field generators for identifying and/or sorting cells, cell components or pathogens, the use of said fields or field generators in the purification of liquids from pathogens, methods or processes for the treatment of infected cells or tumor cells, the use of super-paramagnetically labelled active substances for the preparation of a composition for use in a process for the treatment of infected cells or tumor cells, comprising treatment with a DM field or DM field generator, as well as the combination of super-paramagnetically labelled active substances or superparamagnetically labelled beads with a generator of a DM field. FIG. 3 shows, as example, a microscope ( 12 ) under which a super-paramagnetically labelled sample ( 15 ) is exposed to a DM alternating field by a field generator ( 11 ) and thus the moved labelled objects (e.g. cells) are put into movement and thus become specifically identifiable.

  本发明涉及利用动态磁场（DM场）或DM场发生器识别和/或分选细胞、细胞成分或病原体，利用所述磁场或磁场发生器净化液体中的病原体，治疗受感染细胞或肿瘤细胞的方法或工艺、使用超准磁标记活性物质制备用于治疗受感染细胞或肿瘤细胞过程的组合物，包括使用 DM 场或 DM 场发生器进行处理，以及将超准磁标记活性物质或超准磁标记珠与 DM 场发生器结合使用。图 3 3 举例说明了显微镜 ( 12 )，在该显微镜下，超准磁标记样品( 15 ) 被一个磁场发生器 ( 11 从而使被移动的标记物体（如细胞）处于运动状态，并因此变得可以具体识别。
• 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.