1-[(E)-[(2-chloro-4-fluorophenyl)methylidene]amino]guanidine | 1620237-99-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[(E)-[(2-chloro-4-fluorophenyl)methylidene]amino]guanidine
• 英文别名: (E)-2-(2-chloro-4-fluorobenzylidene)hydrazine-1-carboximidamide；2-[(E)-(2-chloro-4-fluorophenyl)methylideneamino]guanidine
• CAS: 1620237-99-1
• 化学式: C₈H₈ClFN₄
• 分子量: 214.63
• InChiKey: IPLZFWUFKJMOKS-YIXHJXPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  3

文献信息

• [EN] BENZYLIDENEGUANIDINE DERIVATIVES AND THERAPEUTIC USE FOR THE TREATMENT OF PROTEIN MISFOLDING DISEASES<br/>[FR] DÉRIVÉS DE BENZYLIDÈNEGUANIDINE ET LEUR UTILISATION THÉRAPEUTIQUE POUR LE TRAITEMENT DE MALADIES LIÉES À UN MAUVAIS REPLIEMENT DE PROTÉINES
  申请人：MEDICAL RES COUNCIL

  公开号：WO2014108520A1

  公开（公告）日：2014-07-17

  The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein:R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7,OR7and NR8R9; R7, R8and R9 are each independently selected from alkyl, cycloalkyl, aralkyl,cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2,COO-alkyl,aralkyl,SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy;X and Z are each independently CR11, and Y is selected from CR11and N; and R11is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

  本发明涉及一种具有以下结构的化合物（I），或其亪式和/或药用可接受的盐，其中：R1为烷基，Cl，F或Br；R2为H或F；R3从H和烷基中选择；R4从H和C（O）R6中选择；R5为H；或R4和R5连接形成一个杂环基团，该基团可以选择性地用一个或多个R10基团取代；R6从R7，OR7和NR8R9中选择；R7，R8和R9分别独立选择自烷基，环烷基，芳基，环烯基，杂环烷基和芳基，每个基团可以选择性地用一个或多个R10基团取代；每个R10独立选择自卤素，OH，CN，NO2，COO-烷基，芳基，SO2-烷基，SO2-芳基，COOH，CO-烷基，CO-芳基，NH2，NH-烷基，N（烷基）2，CF3，烷基和烷氧基；X和Z各自独立为CR11，Y从CR11和N中选择；R11为H或F；用于治疗与蛋白质错误折叠应激相关的疾病，特别是与错误折叠蛋白质积累相关的疾病。
• [EN] METHODS FOR SELECTING PHOSPHATASE SELECTIVE AND NON-SELECTIVE PHOSPHATASE INHIBITORS<br/>[FR] PROCÉDÉS DE SÉLECTION D'INHIBITEURS SÉLECTIFS ET NON SÉLECTIFS DES PHOSPHATASE
  申请人：MEDICAL RES COUNCIL

  公开号：WO2016162688A1

  公开（公告）日：2016-10-13

  The present invention discloses a method to discover selective inhibitors of phosphatases. Thus the invention provides a method for screening a test compound to determine whether the compound binds a holophosphatase selectively or non-selectively comprising: i) providing a first holophosphatase wherein said holophosphatase is captured/immobilised; ii) testing a test compound for its ability to bind to the first holophosphatase; iii) providing a second holophosphatase wherein said second holophosphatase is captured/immobilised; iv) testing the same test compound for its ability to bind to the second holophosphatase; v) comparing the binding of the test compound to said first holophosphatase with the binding to said second phosphatase wherein a compound that binds a holophosphatase selectively will bind to said first holophosphatase but not said second holophosphatase; or will bind to said second holophosphatase but not said first; or wherein a compound that binds a holophosphatase non-selectively will bind to both said first holophosphatase and said second holophosphatase.

  本发明揭示了一种发现磷酸酶选择性抑制剂的方法。因此，本发明提供了一种筛选测试化合物的方法，以确定该化合物是否选择性或非选择性地结合全磷酸酶，包括：i）提供第一全磷酸酶，其中所述全磷酸酶被捕获/固定；ii）测试测试化合物结合第一全磷酸酶的能力；iii）提供第二全磷酸酶，其中所述第二全磷酸酶被捕获/固定；iv）测试相同的测试化合物结合第二全磷酸酶的能力；v）将测试化合物与第一全磷酸酶和第二全磷酸酶的结合进行比较，其中选择性地结合全磷酸酶的化合物将结合第一全磷酸酶而不结合第二全磷酸酶；或将结合第二全磷酸酶而不结合第一全磷酸酶；或选择性地结合全磷酸酶的化合物将同时结合第一全磷酸酶和第二全磷酸酶。
• Benzylideneguanidine Derivatives and Therapeutic Use for the Treatment of Protein Misfolding Diseases
  申请人：GUEDAT Philippe

  公开号：US20160046589A1

  公开（公告）日：2016-02-18

  The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R 1 is alkyl, Cl, F or Br; R 2 is H or F; R 3 is selected from H and alkyl; R 4 is selected from H and C(O)R 6 ; R 5 is H; or R 4 and R 5 are linked to form a heterocyclic group which is optionally substituted with one or more R 10 groups; R 6 is selected from R 7 , OR 7 and NR 8 R 9 ; R 7 , R 8 and R 9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R 10 groups; each R 10 is independently selected from halogen, OH, CN, NO 2 , COO-alkyl, aralkyl, SO 2 -alkyl, SO 2 -aryl, COOH, CO-alkyl, CO-aryl, NH 2 , NH-alkyl, N(alkyl) 2 , CF 3 , alkyl and alkoxy; X and Z are each independently CR 11 , and Y is selected from CR 11 and N; and R 11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

  本发明涉及式（I）的化合物，或其互变异构体和/或药学上可接受的盐，其中：R1为烷基，氯，氟或溴；R2为氢或氟；R3选自氢和烷基；R4选自氢和C（O）R6；R5为氢；或R4和R5连接形成一个杂环基团，该杂环基团可选地被一个或多个R10基团取代；R6选自R7，OR7和NR8R9；R7，R8和R9各自独立地选自烷基，环烷基，芳基烷基，环烯基，杂环基和芳基，每个基团可选地被一个或多个R10基团取代；每个R10各自独立地选自卤素，羟基，氰基，硝基，COO-烷基，芳基烷基，SO2-烷基，SO2-芳基，COOH，CO-烷基，CO-芳基，NH2，NH-烷基，N（烷基）2，CF3，烷基和烷氧基；X和Z各自独立地为CR11，Y选自CR11和N；R11为氢或氟；用于治疗与蛋白质错折应激相关的疾病，特别是与错折蛋白的积累相关的疾病。
• Benzylideneguanidine derivatives and therapeutic use for the treatment of protein misfolding diseases
  申请人：Medical Research Council

  公开号：US10100020B2

  公开（公告）日：2018-10-16

  The present invention relates to a compound of formula (I), or a tautomer and/or a pharmaceutically acceptable salt thereof, wherein: R1 is alkyl, Cl, F or Br; R2 is H or F; R3 is selected from H and alkyl; R4 is selected from H and C(O)R6; R5 is H; or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups; R6 is selected from R7, OR7 and NR8R9; R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups; each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy; X and Z are each independently CR11, and Y is selected from CR11 and N; and R11 is H or F; for use in treating a disorder associated with protein misfolding stress and in particular associated with accumulation of misfolded proteins.

  本发明涉及式(I)化合物或其同系物和/或药学上可接受的盐，其中：R1 是烷基、Cl、F 或 Br；R2 是 H 或 F；R3 选自 H 和烷基；R4 选自 H 和 C(O)R6；R5 是 H；或 R4 和 R5 连接形成杂环基团，该杂环基团任选被一个或多个 R10 基团取代；R6选自R7、OR7和NR8R9；R7、R8和R9各自独立地选自烷基、环烷基、芳基、环烯基、杂环烯基和芳基，其中每个基团都可选择被一个或多个R10基团取代；每个 R10 独立地选自卤素、OH、CN、NO2、COO-烷基、芳基、SO2-烷基、SO2-芳基、COOH、CO-烷基、CO-芳基、NH2、NH-烷基、N(烷基)2、CF3、烷基和烷氧基；X 和 Z 各自独立地为 CR11，Y 选自 CR11 和 N；R11 为 H 或 F；用于治疗与蛋白质错误折叠应激有关的疾病，特别是与错误折叠蛋白质的积累有关的疾病。
• Inhibitors and their uses
  申请人：MEDICAL RESEARCH COUNCIL

  公开号：US11154519B2

  公开（公告）日：2021-10-26

  The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

  本发明涉及PPP1 R15A和PPP1 R15B的抑制剂及其在治疗中的用途，特别是在治疗通过抑制PPP1 R15A和PPP1 R15B而减轻的疾病状态中的用途，例如与错误折叠蛋白的积累或蛋白抑制紊乱有关的疾病。本发明的化合物包括具有式 IA 的化合物或其药学上可接受的盐，其中 R1a、R3a、R5a、Xa 和 Ya 如本文所定义。