(1R,2S,3R,5R)-3-[(2-amino-6-chloro-5-ethynylpyrimidin-4-yl)amino]-5-(hydroxymethyl)cyclopentane-1,2-diol | 1208109-02-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (1R,2S,3R,5R)-3-[(2-amino-6-chloro-5-ethynylpyrimidin-4-yl)amino]-5-(hydroxymethyl)cyclopentane-1,2-diol
• CAS: 1208109-02-7
• 化学式: C₁₂H₁₅ClN₄O₃
• 分子量: 298.729
• InChiKey: HUJKYDSVFKXINH-YYNOVJQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  125
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,2S,3R,5R)-3-[(2-amino-6-chloro-5-ethynylpyrimidin-4-yl)amino]-5-(hydroxymethyl)cyclopentane-1,2-diol 在 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  Pyridofuran substituted pyrimidine derivatives as HCV replication (replicase) inhibitors

  摘要：

  Introduction of nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzofuran inhibitor 2, resulted in the discovery of the more potent pyridofuran analogue 5. Subsequent introduction of small alkyl and alkoxy ligands into the pyridine ring resulted in further improvements in replicon potency. Replacement of the 4-chloro moiety on the pyrimidine core with a methyl group, and concomitant monoalkylation of the C-2 amino moiety resulted in the identification of several inhibitors with desirable characteristics. Inhibitor 41, from the monosubstituted pyridofuran and inhibitor 50 from the disubstituted series displayed excellent potency, selectivity (GAPDH/MTS CC50) and PK parameters in all species studied, while the selectivity in the thymidine incorporation assay (DNA.CC50) was low. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.021
• 作为产物：
  描述：

  (1R,2S,3R,5R)-3-[(2-amino-6-chloro-5-iodopyrimidin-4-yl)amino]-5-(hydroxymethyl)cyclopentane-1,2-diol 在 Tetraethylammonium fluoride dihydrate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 20.17h， 生成 (1R,2S,3R,5R)-3-[(2-amino-6-chloro-5-ethynylpyrimidin-4-yl)amino]-5-(hydroxymethyl)cyclopentane-1,2-diol
  参考文献：
  名称：

  Substituted pyridine and pyrimidine derivatives and their use in treating viral infections

  摘要：

  本发明提供了式(I)的化合物：以及所述化合物的互变异构体、异构体和酯，以及所述化合物的药学上可接受的盐、溶剂化合物和前药，其中R、R1、X、Y、Z、R2、R3、R4、R5、R6、R7、R8、R9、R18、R19和n中的每个都是独立选择并如本文所定义。还提供了包含这些化合物的组合物。本发明的化合物作为HCV的抑制剂是有效的，并且在治疗或预防病毒感染和与病毒相关的疾病或紊乱方面，单独或与其他治疗剂一起使用是有用的。

  公开号：

  US09433621B2

文献信息

• [EN] SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS<br/>[FR] DÉRIVÉS DE PYRIDINE ET PYRIMIDINE SUBSTITUÉES ET LEUR UTILISATION DANS LE TRAITEMENT D'INFECTIONS VIRALES
  申请人：SCHERING CORP

  公开号：WO2010022121A1

  公开（公告）日：2010-02-25

  The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.

  本发明提供了式(I)的化合物：以及所述化合物的互变异构体、同分异构体和酯，以及所述化合物的药学上可接受的盐、溶剂化合物和前药，其中R、R1、X、Y、Z、R2、R3、R4、R5、R6、R7、R8、R9、R18、R19和n中的每个均独立选择并如本文所定义。还提供了包含这些化合物的组合物。本发明的化合物作为HCV的抑制剂是有效的，并且在治疗或预防病毒感染和与病毒相关的疾病或紊乱方面，单独或与其他治疗剂一起使用是有用的。
• [EN] ETHYNYL-SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS<br/>[FR] DÉRIVÉS DE PYRIDINE ET DE PYRIMIDINE À SUBSTITUTION ÉTHYLYLE ET LEUR UTILISATION DANS LE TRAITEMENT D'INFECTIONS VIRALES
  申请人：SCHERING CORP

  公开号：WO2010022125A1

  公开（公告）日：2010-02-25

  The present invention provides compounds of Formula (I): (Chemical formula should be inserted here as it appears on abstract in paper form) (I) and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein wherein each of R, R1, X, Y, Z, R2, R3, R4, R5, R6, R7, R8, R9, R18, R19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing dieases or disorders such as viral infections and virus-related disorders.

  本发明提供了化合物的公式(I)：(化学式应按照纸质摘要中的形式插入) (I)及其互变异构体、同分异构体和酯，以及所述化合物的药用可接受的盐、溶剂化合物和前药，其中R、R1、X、Y、Z、R2、R3、R4、R5、R6、R7、R8、R9、R18、R19和n中的每个均独立选择并按照此处定义。还提供了包含这些化合物的组合物。本发明的化合物作为HCV的抑制剂是有效的，并且单独或与其他治疗剂一起，在治疗或预防病毒感染和与病毒相关的疾病或疾病方面是有用的。
• Novel substituted pyrimidines as HCV replication (replicase) inhibitors
  作者：Cecil D. Kwong、Jeremy L. Clark、Anita T. Fowler、Feng Geng、Hollis S. Kezar、Abhijit Roychowdhury、Robert C. Reynolds、Joseph A. Maddry、Subramaniam Ananthan、John A. Secrist、Neng-Yang Shih、John J. Piwinski、Cheng Li、Boris Feld、Hsueh-Cheng Huang、Xiao Tong、F. George Njoroge、Ashok Arasappan

  DOI：10.1016/j.bmcl.2011.11.091

  日期：2012.1

  Compound I was identified as a HCV replication inhibitor from screening/early SAR triage. Potency improvement was achieved via modulation of substituent on the 5-azo linkage. Due to potential toxicological concern, the 5-azo linkage was replaced with 5-alkenyl or 5-alkynyl moiety. Analogs containing the 5-alkynyl linkage were found to be potent inhibitors of HCV replication. Further evaluation identified compounds 53 and 63 with good overall profile, in terms of replicon potency, selectivity and in vivo characteristics. Initial target engagement studies suggest that these novel carbanucleoside-like derivatives may inhibit the HCV replication complex (replicase). (C) 2011 Elsevier Ltd. All rights reserved.
• SUBSTITUTED PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2536410B1

  公开（公告）日：2015-09-23
• SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
  申请人：Arasappan Ashok

  公开号：US20110318305A1

  公开（公告）日：2011-12-29

  The present invention provides compounds of Formula (I): and tautomers, isomers, and esters of said compounds, and pharmaceutically acceptable salts, solvates, and prodrugs of said compounds, wherein each of R, R 1 , X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 18 , R 19 and n is selected independently and as defined herein. Compositions comprising such compounds are also provided. The compounds of the invention are effective as inhibitors of HCV, and are useful, alone and together with other therapeutic agents, in treating or preventing diseases or disorders such as viral infections and virus-related disorders.