[(3aS,4R,6R,6aR)-4-[[5-(1,3-benzothiazol-2-yl)-6-methyl-2-methylsulfonylpyrimidin-4-yl]amino]-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol | 1208987-84-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: [(3aS,4R,6R,6aR)-4-[[5-(1,3-benzothiazol-2-yl)-6-methyl-2-methylsulfonylpyrimidin-4-yl]amino]-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol
• CAS: 1208987-84-1
• 化学式: C₂₂H₂₆N₄O₅S₂
• 分子量: 490.604
• InChiKey: AWWSQRLGPRBDLD-FOZNTRSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  160
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [(3aS,4R,6R,6aR)-4-[[5-(1,3-benzothiazol-2-yl)-6-methyl-2-methylsulfonylpyrimidin-4-yl]amino]-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol 在 sodium azide 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.25h， 生成 4-N-[(3aS,4R,6R,6aR)-6-(aminomethyl)-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-5-(1,3-benzothiazol-2-yl)-6-methyl-2-N-(thiophen-2-ylmethyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
  [FR] DÉRIVÉS DE PYRIDINE ET PYRIMIDINE SUBSTITUÉES ET LEUR UTILISATION DANS LE TRAITEMENT D'INFECTIONS VIRALES

  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、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。

  公开号：

  WO2010022121A1
• 作为产物：
  描述：

  4-氯-5-碘-6-甲基-2-(甲硫基)嘧啶 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 甲烷磺酸 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 丙酮 为溶剂， 反应 2.0h， 生成 [(3aS,4R,6R,6aR)-4-[[5-(1,3-benzothiazol-2-yl)-6-methyl-2-methylsulfonylpyrimidin-4-yl]amino]-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]methanol
  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

• 5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors
  作者：Ashok Arasappan、Frank Bennett、Vinay Girijavallabhan、Yuhua Huang、Regina Huelgas、Carmen Alvarez、Lei Chen、Stephen Gavalas、Seong-Heon Kim、Aneta Kosinski、Patrick Pinto、Razia Rizvi、Randall Rossman、Bandarpalle Shankar、Ling Tong、Francisco Velazquez、Srikanth Venkatraman、Vishal A. Verma、Joseph Kozlowski、Neng-Yang Shih、John J. Piwinski、Malcolm MacCoss、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、Cheng Li、Robert Chase、Stephanie Curry、Hsueh-Cheng Huang、Xiao Tong、F. George Njoroge

  DOI：10.1016/j.bmcl.2012.03.036

  日期：2012.5

  Based on a previously identified HCV replication (replicase) inhibitor 1, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a methyl group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound 16 that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration. Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol. (C) 2012 Elsevier Ltd. All rights reserved.
• 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.
• US9433621B2
  申请人：——

  公开号：US9433621B2

  公开（公告）日：2016-09-06