N-(1-Methanesulfonyl-piperidin-4-yl)-guanidine | 1057323-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-(1-Methanesulfonyl-piperidin-4-yl)-guanidine
• 英文别名: N-(1-Methanesulfonyl-piperidin-4-yl)guanidine；2-(1-methylsulfonylpiperidin-4-yl)guanidine
• CAS: 1057323-20-2
• 化学式: C₇H₁₆N₄O₂S
• 分子量: 220.296
• InChiKey: OWRMQSGKIUDABE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(1-Methanesulfonyl-piperidin-4-yl)-guanidine 、 2-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-3-phenylamino-acrylonitrile 在 sodium methylate 作用下， 以 乙醇 为溶剂， 生成 5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)-2-N-(1-methylsulfonylpiperidin-4-yl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Identification and SAR of novel diaminopyrimidines. Part 2: The discovery of RO-51, a potent and selective, dual P2X3/P2X2/3 antagonist for the treatment of pain

  摘要：

  The purinoceptor subtypes P2X(3) and P2X(2/3) have been shown to play a pivotal role in models of various pain conditions. Identification of a potent and selective dual P2X(3)/P2X(2/3) diaminopyrimidine antagonist RO-4 prompted subsequent optimization of the template. This paper describes the SAR and optimization of the diaminopyrimidine ring and particularly the substitution of the 2-amino group. The discovery of the highly potent and drug-like dual P2X(3)/P2X(2/3) antagonist RO-51 is presented. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.097

文献信息

• Diaminopyrimidines as P2X3 and P2X2/3 antagonists
  申请人：Broka Allen Chris

  公开号：US20050209260A1

  公开（公告）日：2005-09-22

  Compounds and methods for treating diseases mediated by a P2X 3 and/or a P2X 2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein D, X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein.

  用于治疗由P2X3和/或P2X2/3受体拮抗剂介导的疾病的治疗化合物和方法，该方法包括向有需要的受试者施用有效量的式I化合物：或其药学上可接受的盐、溶剂化物或前药，其中D、X、Y、R1、R2、R3、R4、R5、R6、R7和R8如本文所定义。
• Methods of using diaminopyrimidine P2X3 and P2X2/3 receptor modulators for treatment of respiratory and gastrointestinal diseases
  申请人：Broka Allen Chris

  公开号：US20070049609A1

  公开（公告）日：2007-03-01

  Methods for treating respiratory and gastrointestinal diseases mediated by a P2X 3 and/or a P2X 2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein D, X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein.

  用于治疗由P2X3和/或P2X2/3受体拮抗剂介导的呼吸系统和胃肠道疾病的方法，包括向有此需要的受试者施用有效量的式(I)化合物：或其药学上可接受的盐，其中D、X、Y、R1、R2、R3、R4、R5、R6、R7和R8如本文所定义。
• [EN] N-(1-(METHYLSULFONYL)PIPERIDIN-4-YL)-4,5-DI HYDRO-1H-IMIDAZO[4,5-H]QUINAZOLIN-8-AMINE DERIVATIVES AND RELATED COMPOUNDS AS CYCLIN-DEPENDENT KINASE 2 (CDK2) INHIBITORS FOR TREATING CANCER<br/>[FR] DÉRIVÉS DE N-(1-(MÉTHYLSULFONYL)PIPÉRIDIN-4-YL)-4,5-DI HYDRO-1H-IMIDAZO[4,5-H]QUINAZOLIN-8-AMINE ET COMPOSÉS APPARENTÉS UTILISÉS EN TANT QU'INHIBITEURS DE KINASE 2 DÉPENDANTE DES CYCLINES (CDK2) POUR LE TRAITEMENT DU CANCER
  申请人：INCYTE CORP

  公开号：WO2020223469A1

  公开（公告）日：2020-11-05

  The present application provid es tricyclic amine compounds of formula (I) as inhibitors of cyclin-dependent kinase 2 (CDK2) for treating cancer. Preferred compounds are N-(1-(methylsulfonyl)piperidin-4- yl)-4,5-dihydro-lH-imidazo[4,5-h]quinazolin-8-amine and the corresponding 6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine, 6,8- dihydropyrazolo[4',3':4,5]pyrano[3,2-d]pyrimidin-2-amine and 1,4- dihydroimidazo[4',5': 4,5]pyrano[3,2-d]pyrimidin-8-amine derivatives of formulae (IVa) to (IVd). The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 128 to 166; examples 1 to 32, A and B1 to B10; table 1). Exemplary compound are e.g.: N-(1-(ethylsulfonyl)piperidin-4-yl)-l,2-dimethyl-4,5-dihydro-1H- imidazo[4,5-h]quinazolin-8-amine (example 1) 8-Methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydro-5H- pyrazolo[3,4-h]quinazolin-2-amine (example 9) 8-Methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8- dihydropyrazolo[4',3':4,5]pyrano[3,2-d]pyrimidin-2-amine (example 10) 1-cyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-l,4- dihydroimidazo[4',5':4,5]pyrano [3,2-d]pyrimidin-8-amine (example 26).

  本申请提供了化学式(I)的三环胺化合物作为cyclin-dependent kinase 2 (CDK2)的抑制剂，用于治疗癌症。首选化合物为N-(1-(甲磺酰基)哌啶-4-基)-4,5-二氢-1H-咪唑并[4,5-h]喹唑啉-8-胺以及相应的6,8-二氢-5H-吡唑并[3,4-h]喹唑啉-2-胺、6,8-二氢吡唑并[4',3':4,5]吡喃[3,2-d]嘧啶-2-胺和1,4-二氢咪唑并[4',5':4,5]吡喃[3,2-d]嘧啶-8-胺的衍生物，化学式为(IVa)到(IVd)。本说明揭示了示例化合物的合成和表征以及其药理学数据（例如，第128至166页；示例1至32，A和B1至B10；表1）。示例化合物包括：N-(1-(乙磺酰基)哌啶-4-基)-1,2-二甲基-4,5-二氢-1H-咪唑并[4,5-h]喹唑啉-8-胺（示例1）、8-甲基-N-(1-(甲磺酰基)哌啶-4-基)-6,8-二氢-5H-吡唑并[3,4-h]喹唑啉-2-胺（示例9）、8-甲基-N-(1-(甲磺酰基)哌啶-4-基)-6,8-二氢吡唑并[4',3':4,5]吡喃[3,2-d]嘧啶-2-胺（示例10）、1-环丙基-N-(1-(甲磺酰基)哌啶-4-基)-1,4-二氢咪唑并[4',5':4,5]吡喃[3,2-d]嘧啶-8-胺（示例26）。
• DIAMINOPYRIMIDINES AS P2X3 AND P2X2/3 ANTAGONISTS
  申请人：Broka Chris Allen

  公开号：US20110077242A1

  公开（公告）日：2011-03-31

  Compounds and methods for treating diseases mediated by a P2X 3 and/or a P2X 2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein D, X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein.

  本发明涉及化合物和方法，用于治疗由P2X3和/或P2X2/3受体拮抗剂介导的疾病，其中所述方法包括向需要该治疗的受体中施用化合物I式的有效量，或其药学上可接受的盐、溶剂或前药，其中D、X、Y、R1、R2、R3、R4、R5、R6、R7和R8如本文所定义。
• METHODS OF USING DIAMINOPYRIMIDINE AS P2X3 AND P2X2/3 RECEPTOR MODULATORS FOR TREATMENT OF RESPIRATORY AND GASTROINTESTINAL DISEASES
  申请人：Broka Chris Allen

  公开号：US20120122859A1

  公开（公告）日：2012-05-17

  Methods for treating respiratory and gastrointestinal diseases mediated by a P2X 3 and/or a P2X 2/3 receptor antagonist, the methods comprising administering to a subject in need thereof an effective amount of a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein D, X, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined herein.

  治疗由P2X3和/或P2X2/3受体拮抗剂介导的呼吸道和胃肠道疾病的方法，包括向需要治疗的个体施用式(I)的化合物的有效量或其药学上可接受的盐，其中D、X、Y、R1、R2、R3、R4、R5、R6、R7和R8如此定义。