(1R,2R)-2-(2-amino-5-fluorophenoxy)cyclohexan-1-ol | 1332632-92-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (1R,2R)-2-(2-amino-5-fluorophenoxy)cyclohexan-1-ol
• 英文别名: (1R,2R)-2-(2-amino-5-fluorophenoxy)cyclohexanol；(R,R)-4-fluoro-2-(2-hydroxycyclohexyloxy)-aniline；(R,R)-4-Fluoro-2-(2-Hydroxycyclohexyloxy)-anilin
• CAS: 1332632-92-4
• 化学式: C₁₂H₁₆FNO₂
• 分子量: 225.263
• InChiKey: YBNJJTJCWYDBCZ-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-(2-amino-5-fluorophenoxy)cyclohexan-1-ol 、 N-[3-(dimethylamino)propyl]-7-methylsulfanylthiazolo[5,4-d]pyrimidine-2-carboxamide 在 三氟乙酸 作用下， 以 异丙醇 为溶剂， 反应 0.75h， 以26%的产率得到N-[3-(dimethylamino)propyl]-7-[4-fluoro-2-[(1R,2R)-2-hydroxycyclohexoxy]anilino]thiazolo[5,4-d]pyrimidine-2-carboxamide
  参考文献：
  名称：

  [EN] FUSED THIAZOLOPYRIMIDINE DERIVATIVES AS MNKS INHIBITORS
  [FR] UTILISATION DE DÉRIVÉS THIAZOLOPYRIMIDINE FUSIONNÉS COMME INHIBITEURS DE MNSK

  摘要：

  本发明涉及公式I和H的化合物，或其药用盐或酯。该发明的进一步方面涉及药物组合物以及所述化合物在治疗未受控制的细胞生长、增殖和/或存活、不当的细胞免疫反应、不当的细胞炎症反应或神经退行性疾病，更好地说是tau病变疾病，甚至更好地说是阿尔茨海默病的治疗用途。

  公开号：

  WO2017085484A1
• 作为产物：
  描述：

  (1R,2R)-2-(5-fluoro-2-nitrophenoxy)cyclohexan-1-ol 在 5%-palladium/activated carbon 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 5.0h， 生成 (1R,2R)-2-(2-amino-5-fluorophenoxy)cyclohexan-1-ol
  参考文献：
  名称：

  [EN] 4 - [CYCLOALKYLOXY (HETERO) ARYLAMINO] THIENO [2, 3 - D] PYRIMIDINES HAVING MNKL/ MNK2 INHIBITING ACTIVITY FOR PHARMACEUTICAL COMPOSITIONS
  [FR] 4-[CYCLOALKYLOXY(HÉTÉRO)ARYLAMINO]THIÉNO[2,3-D]PYRIMIDINES AYANT UNE ACTIVITÉ D'INHIBITION DE MNK1/MNK2 POUR DES COMPOSITIONS PHARMACEUTIQUES

  摘要：

  本发明涉及一种新型噻吩嘧啶化合物，其一般式为（I），包括这些化合物的药物组合物以及它们在预防和/或治疗可能受到Mnk1和/或Mnk2（Mnk2a或Mnk2b）的激酶活性抑制影响的疾病中的治疗用途。

  公开号：

  WO2011104334A1

文献信息

• CYCLOALKYL CONTAINING THIENOPYRIMIDINES FOR PHARMACEUTICAL COMPOSITIONS
  申请人：LEHMANN-LINTZ Thorsten

  公开号：US20110217311A1

  公开（公告）日：2011-09-08

  The present invention relates to novel thienopyrimidine compounds of general formula pharmaceutical compositions comprising these compounds and their therapeutic use for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2 a or Mnk2 b ) and/or variants thereof.

  本发明涉及新型噻吩并嘧啶化合物，其一般公式，包含这些化合物的药物组合物，以及它们在预防和/或治疗可通过抑制Mnk1和/或Mnk2（Mnk2a或Mnk2b）及其变体的激酶活性而影响的疾病中的治疗用途。
• [EN] PYRROPYRIMIDINE COMPOUNDS AS MNKS INHIBITORS<br/>[FR] COMPOSÉS DE PYRROPYRIMIDINE EN TANT QU'INHIBITEURS DE MNKS
  申请人：MEDICAL RES COUNCIL TECH

  公开号：WO2017085483A1

  公开（公告）日：2017-05-26

  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 Ζ1, Z3 and Z4 are ail 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.

  本发明涉及以下式I的化合物，或其药学上可接受的盐或酯，其中：R1从H和CO-NR8R9中选择，其中R8和R9各自独立地从H、烷基、环烷基和单环或双环杂环烷基中选择，其中所述烷基基团可以选择性地被一个或多个R12基团取代，所述杂环烷基可以选择性地被R10或R12取代；或R8和R9与它们连接，连同它们附着的氮一起形成一个可能含有一个或多个额外杂原子的杂环烷基基团，并且可以选择性地被一个或多个基团选择自R10和(CH2)mR12；R2从H和烷基中选择，其中所述烷基基团可以选择性地被一个或多个R12基团取代；R3从烷基、环烷基和杂环烷基中选择，每个都可以选择性地被卤、OH或烷氧基取代；Z1、Z2、Z3和Z4都是C；R4、R5、R6和R7各自独立地从H、烷基、CN、NO2、OH、烷氧基、NHCO-烷基、卤和卤代烷基中选择；或Ζ1、Z3和Z4都是C，Z2是N，R5不存在，R4、R6和R7如上所定义；或Z1、Z3和Z4都是C，Z1是N，R4不存在，R5、R6和R7如上所定义；每个R10和R11独立地是烷基；每个R12独立地从CO2R10、COOH、OH、烷氧基、卤代烷基、NH2、NHR10、NR10R11、杂芳基和杂环烷基中选择；R13是H或卤。进一步方面涉及所述化合物在治疗细胞生长、增殖和/或存活失控的疾病、不当的细胞免疫反应、不当的细胞炎症反应或神经退行性疾病，优选是tau病变，甚至更优选是阿尔茨海默病中的药物组合物和治疗用途。
• Cycloalkyl containing thienopyrimidines for pharmaceutical compositions
  申请人：Lehmann-Lintz Thorsten

  公开号：US08754079B2

  公开（公告）日：2014-06-17

  The present invention relates to novel thienopyrimidine compounds of general formula pharmaceutical compositions comprising these compounds and their therapeutic use for the prophylaxis and/or treatment of diseases which can be influenced by the inhibition of the kinase activity of Mnk1 and/or Mnk2 (Mnk2a or Mnk2b) and/or variants thereof.

  本发明涉及一种新型噻唑嘧啶化合物，其一般式如下，以及含有这些化合物的药物组成物，并且这些化合物的治疗用途为预防和/或治疗可以受到Mnk1和/或Mnk2（Mnk2a或Mnk2b）及/或其变体激酶活性抑制影响的疾病。
• 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 thiazolopyrimidine derivatives as MNKS inhibitors
  申请人：LIFEARC

  公开号：US10669284B2

  公开（公告）日：2020-06-02

  The present invention relates to compounds of formulae I and H, or pharmaceutically acceptable salts or esters thereof. Further aspects of the invention 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 和 H 的化合物或其药学上可接受的盐或酯。本发明的其他方面涉及所述化合物在治疗细胞生长、增殖和/或存活失控疾病、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）中的药物组合物和治疗用途。