4-chloro-5-isopropyl-pyrrolo[3,2-d]pyrimidine | 919278-25-4

• 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-isopropyl-pyrrolo[3,2-d]pyrimidine
• 英文别名: 4-Chloro-5-isopropyl-5H-pyrrolo[3,2-d]pyrimidine；4-chloro-5-propan-2-ylpyrrolo[3,2-d]pyrimidine
• CAS: 919278-25-4
• 化学式: C₉H₁₀ClN₃
• 分子量: 195.651
• InChiKey: QTMDSMZZOKWMBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-chloro-5-isopropyl-pyrrolo[3,2-d]pyrimidine 、 trans-dimethylcyclohexane-1,4-diamine 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 10.0h， 以26%的产率得到trans-N,N-dimethyl-N'-(5-isopropyl-pyrrolo[3,2-d]pyrimidin-4-yl)-1,4-cyclohexanediamine
  参考文献：
  名称：

  Optimization of permeability in a series of pyrrolotriazine inhibitors of IRAK4

  摘要：

  We have developed a series of orally efficacious IRAK4 inhibitors, based on a scaffold hopping strategy and using rational structure based design. Efforts to tackle low permeability and high efflux in our previously reported pyrrolopyrimidine series (Scott et al., 2017) led to the identification of pyrrolotriazines which contained one less formal hydrogen bond donor and were intrinsically more lipophilic. Further optimisation of substituents on this pyrrolotriazine core culminated with the discovery of 30 as a promising in vivo probe to assess the potential of IRAK4 inhibition for the treatment of MyD88 mutant DLBCL in combination with a BTK inhibitor. When tested in an ABC-DLBCL model with a dual MyD88/CD79 mutation (OCI-LY10), 30 demonstrated tumour regressions in combination with ibrutinib. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.01.008
• 作为产物：
  描述：

  2-碘代丙烷 、 4-氯吡咯并[2,3-D]嘧啶 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 以75%的产率得到4-chloro-5-isopropyl-pyrrolo[3,2-d]pyrimidine
  参考文献：
  名称：

  WO2007/4749

  摘要：

  公开号：

文献信息

• FUSED HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2103620A1

  公开（公告）日：2009-09-23

  The present invention provides a fused heterocyclic compound having a tyrosine kinase inhibitory action, which is represented by the formula: wherein R1 is a hydrogen atom, a halogen atom, or an optionally substituted group bonded via a carbon atom, a nitrogen atom or an oxygen atom; R2 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom or a sulfur atom, or R1 and R2, or R2 and R3 are optionally bonded to each other to form an optionally substituted ring structure; R3 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3 is optionally bonded to the carbon atom on ring A to form an optionally substituted ring structure; ring A is an optionally substituted benzene ring; and ring B is (i) an optionally substituted fused ring, or (ii) a pyridine ring having optionally substituted carbamoyl (the pyridine ring is optionally further substituted).

  本发明提供了一种具有酪氨酸激酶抑制作用的融合杂环化合物，其化学式如下： 其中 R1是氢原子、卤素原子或通过碳原子、氮原子或氧原子键合的可选择取代基； R2是氢原子，或通过碳原子或硫原子键合的可选择取代基，或 R1和R2，或R2和R3可选择键合在一起形成可选择取代的环结构； R3是氢原子或可选择取代的脂肪烃基，或 R3可选择键合到环A上的碳原子上形成可选择取代的环结构； 环A是可选择取代的苯环；环B是 (i) 可选择取代的融合环，或 (ii) 具有可选择取代的氨基甲酰基的吡啶环（吡啶环可进一步取代）。
• 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。
• FUSED HETEROCYCLIC DERIVATIVES AND USE THEREOF
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1904498A1

  公开（公告）日：2008-04-02
• PYRROPYRIMIDINE COMPOUNDS AS MNKS INHIBITORS
  申请人：LifeArc

  公开号：EP3377494B1

  公开（公告）日：2021-03-03