4-chloro-5-(2-methoxyethyl)pyrrolo[3,2-d]pyrimidine | 919278-16-3

• 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: 4-chloro-5-(2-methoxyethyl)pyrrolo[3,2-d]pyrimidine
• 英文别名: 4-chloro-5-(2-methoxyethyl)-5H-pyrrolo[3,2-d]pyrimidine
• CAS: 919278-16-3
• 化学式: C₉H₁₀ClN₃O
• 分子量: 211.651
• InChiKey: JKCWKZMRCKHVFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-amino-2-chlorophenoxy)-N-(tert-butyl)-2-fluorobenzamide 、 4-chloro-5-(2-methoxyethyl)pyrrolo[3,2-d]pyrimidine 以 异丙醇 为溶剂， 生成 N-(tert-butyl)-5-(2-chloro-4-{[5-(2-methoxyethyl)-5H-pyrrolo[3,2-d]pyrimidin-4-yl]amino}phenoxy)-2-fluorobenzamide
  参考文献：
  名称：

  FUSED HETEROCYCLIC COMPOUND

  摘要：

  本发明提供了一种化合物，其表示为以下式子：其中，R1a是氢原子，R2a是一个C1-6烷基，被一个表示为—NR6a—CO—（CH2）n—SO2—的基团取代，该基团可选地卤代C1-4烷基，其中n是1至4的整数，R6a是氢原子或C1-4烷基，—（CH2）n—可选地被C1-4烷基取代，R3a是氢原子或C1-6烷基，R4a是卤原子或C1-6烷基，R5a是卤原子或C1-6烷基，Xa是氢原子或卤原子，或其盐。本发明的化合物具有卓越的酪氨酸激酶抑制作用，高度安全，并且作为药物产品完全令人满意。

  公开号：

  US20100216788A1
• 作为产物：
  描述：

  4-氯吡咯并[2,3-D]嘧啶 、 2-溴乙基甲基醚 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 以96%的产率得到4-chloro-5-(2-methoxyethyl)pyrrolo[3,2-d]pyrimidine
  参考文献：
  名称：

  WO2007/4749

  摘要：

  公开号：

文献信息

• N-Phenyl-N′-[4-(5H-pyrrolo[3,2-d]pyrimidin-4-yloxy)phenyl]ureas as novel inhibitors of VEGFR and FGFR kinases
  作者：Yuya Oguro、Naoki Miyamoto、Terufumi Takagi、Kengo Okada、Yoshiko Awazu、Hiroshi Miki、Akira Hori、Keiji Kamiyama、Shinichi Imamura

  DOI：10.1016/j.bmc.2010.08.042

  日期：2010.10.15

  co-crystal structure analysis of VEGFR2 and 1b. Among the compounds synthesized, urea derivative 11l having a piperazine moiety on the terminal benzene ring showed strong inhibitory activity against FGFR1 kinase as well as VEGFR2 kinase. A binding model of 11l complexed with VEGFR2 suggested that the piperazine moiety forms additional interactions with Ile1025 and His1026.

  我们最近报道了吡咯并[3,2- d ]嘧啶衍生物1a和1b作为血管内皮生长因子受体（VEGFR），血小板衍生生长因子受体（PDGFR）和Tie-2激酶的有效三重抑制剂的发现。为了鉴定对成纤维细胞生长因子受体（FGFR）激酶具有强抑制活性的化合物，使用VEGFR2和1b的共晶体结构分析进行了进一步修饰。在合成的化合物中，在末端苯环上具有哌嗪部分的尿素衍生物11l显示出对FGFR1激酶和VEGFR2激酶的强抑制活性。11l的绑定模型 与VEGFR2复合表明哌嗪部分与Ile1025和His1026形成额外的相互作用。
• Fused Heterocyclic Derivatives and Use Thereof
  申请人：Imamura Shinichi

  公开号：US20090137580A1

  公开（公告）日：2009-05-28

  The present invention provides a fused heterocyclic derivative showing a potent kinase inhibitory activity and use thereof. A compound represented by the formula: wherein ring A is an optionally substituted pyrrole ring, X is an optionally substituted CH, Y is an optionally substituted CH or nitrogen atom, Z is an optionally substituted divalent hydrocarbon group or optionally substituted divalent heterocyclic group, T is a single bond or an optionally substituted C 1-3 alkylene group, and U is an optionally substituted amido group, an optionally substituted sulfonamido group, an optionally substituted ureido group, an optionally substituted carbamoyl group or an optionally substituted thioureido group, or a salt thereof, and a pharmaceutical agent containing the compound or a prodrug thereof, which is a kinase (VEGFR, VEGFR2, PDGFR, TIE2) inhibitor, an angiogenesis inhibitor, an agent for the prophylaxis or treatment of cancer, an agent for inhibiting growth of cancer or an agent for suppressing metastasis of cancer.

  本发明提供了一种融合的杂环衍生物，具有强大的激酶抑制活性及其用途。该化合物由以下公式表示： 其中，环A是可选的取代吡咯环，X是可选的取代的CH，Y是可选的取代的CH或氮原子，Z是可选的取代的二价碳氢基团或可选的取代的二价杂环基团，T是单键或可选的取代的C1-3烷基团，U是可选的取代的酰胺基团、可选的取代的磺酰胺基团、可选的取代的脲基团、可选的取代的氨基甲酰基团或可选的取代的硫脲基团，或其盐，以及含有该化合物或其前药的药物制剂，该制剂是激酶(VEGFR、VEGFR2、PDGFR、TIE2)抑制剂、血管生成抑制剂、预防或治疗癌症的药物、抑制癌症生长的药物或抑制癌症转移的药物。
• Pyrropyrimidine compounds as MNKs inhibitors
  申请人：LIFEARC

  公开号：US10604524B2

  公开（公告）日：2020-03-31

  The present invention relates to compounds of formulae I, or pharmaceutically acceptable salts or esters thereof, wherein: R1 is selected from H and CO—NR8R9, wherein R8 and R9 are each independently selected from H, alkyl, cycloalkyl and mono or bicyclic heterocycloalkyl, wherein said alkyl group is optionally substituted by one or more R12 groups, and said heterocycloalkyl is optionally substituted by R10 or R12; or R8 and R9 are linked, together with the nitrogen to which they are attached, to form a heterocycloalkyl group optionally containing one or more additional heteroatoms, and optionally substituted by one or more groups select from R10 and (CH2)mR12; R2 is selected from H and alkyl, wherein said alkyl group is optionally substituted by one or more R12 groups; R3 is selected from alkyl, cycloalkyl and heterocycloalkyl, each of which may be optionally substituted by halo, OH or alkoxy; Z1, Z2, Z3 and Z4 are all C; R4, R5, R6 and R7 are each independently selected from H, alkyl, CN, NO2, OH, alkoxy, NHCO-alkyl, halo and haloalkyl; or Z1, Z3 and Z4 are all C, Z2 is N, R5 is absent and R4, R6 and R7 are as defined above; or Z1, Z3 and Z4 are all C, Z1 is N, R4 is absent and R5, R6 and R7 are as defined above; each R10 and R11 is independently alkyl; each R12 is independently selected from CO2R10, COOH, OH, alkoxy, haloalkyl, NH2, NHR10, NR10R11, heteroaryl and heterocycloalkyl; R13 is H or halo. Further aspects relate to pharmaceutical compositions and therapeutic uses of said compounds in the treatment of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, inappropriate cellular inflammatory responses, or neurodegenerative disorders, preferably tauopathies, even more preferably, Alzheimer's disease.

  本发明涉及式 I 的化合物或其药学上可接受的盐或酯，其中：R1选自H和CO-NR8R9，其中R8和R9各自独立地选自H、烷基、环烷基和单环或双环杂环烷基，其中所述烷基任选被一个或多个R12基团取代，所述杂环烷基任选被R10或R12取代；或 R8 和 R9 与所连接的氮相连，形成杂环烷基，该杂环烷基可选择含有一个或多个额外的杂原子，并可选择被一个或多个选自 R10 和 (CH2)mR12 的基团取代； R2 选自 H 和烷基，其中所述烷基可选择被一个或多个 R12 基团取代；R3选自烷基、环烷基和杂环烷基，其中每个环烷基可任选被卤代、OH或烷氧基取代；Z1、Z2、Z3和Z4均为C；R4、R5、R6和R7各自独立选自H、烷基、CN、NO2、OH、烷氧基、NHCO-烷基、卤代和卤代烷基；或Z1、Z3和Z4均为C，Z2为N，R5不存在，R4、R6和R7如上定义；或 Z1、Z3 和 Z4 均为 C，Z1 为 N，R4 不存在，R5、R6 和 R7 如上所定义；每个 R10 和 R11 独立为烷基；每个 R12 独立选自 CO2R10、COOH、OH、烷氧基、卤代烷基、NH2、NHR10、NR10R11、杂芳基和杂环烷基；R13 为 H 或卤代。进一步的方面涉及所述化合物的药物组合物和治疗用途，用于治疗细胞生长、增殖和/或存活失控的疾病、不适当的细胞免疫反应、不适当的细胞炎症反应或神经退行性疾病，优选牛磺酸病，更优选阿尔茨海默病。
• PYRROPYRIMIDINE COMPOUNDS AS MNKS INHIBITORS
  申请人：LifeArc

  公开号：EP3377494B1

  公开（公告）日：2021-03-03
• Pyrropyrimidine Compounds As MNKS Inhibitors
  申请人：LIFEARC

  公开号：US20180346469A1

  公开（公告）日：2018-12-06

  The present invention relates to compounds of formulae I, or pharmaceutically acceptable salts or esters thereof, wherein: R 1 is selected from H and CO—NR 8 R 9 , wherein R 8 and R 9 are each independently selected from H, alkyl, cycloalkyl and mono or bicyclic heterocycloalkyl, wherein said alkyl group is optionally substituted by one or more R 12 groups, and said heterocycloalkyl is optionally substituted by R 10 or R 12 ; or R 8 and R 9 are linked, together with the nitrogen to which they are attached, to form a heterocycloalkyl group optionally containing one or more additional heteroatoms, and optionally substituted by one or more groups select from R 10 and (CH 2 ) m R 12 ; R 2 is selected from H and alkyl, wherein said alkyl group is optionally substituted by one or more R 12 groups; R 3 is selected from alkyl, cycloalkyl and heterocycloalkyl, each of which may be optionally substituted by halo, OH or alkoxy; Z 1 , Z 2 , Z 3 and Z 4 are all C; R 4 , R 5 , R 6 and R 7 are each independently selected from H, alkyl, CN, NO 2 ,OH, alkoxy, NHCO-alkyl, halo and haloalkyl; or Z 1 , Z 3 and Z 4 are all C, Z 2 is N, R 5 is absent and R 4 , R 6 and R 7 are as defined above; or Z 1 , Z 3 and Z 4 are all C, Z 1 is N, R 4 is absent and R 5 , R 6 and R 7 are as defmed above; each R 10 and R11 is independently alkyl; each R 12 is independently selected from CO 2 R 10 , COOH, OH, alkoxy, haloalkyl, NH 2 , NHR 10 , NR 10 R 11 , heteroaryl and heterocycloalkyl; R 13 is H or halo. Further aspects relate to pharmaceutical compositions and therapeutic uses of said compounds in the treatment of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, inappropriate cellular inflammatory responses, or neurodegenerative disorders, preferably tauopathies, even more preferably, Alzheimer's disease.