(1R,2S,3R,5S)-3-[[2-[cyclopropylmethyl(methyl)amino]-6-methyl-5-(4-methylthiazolo[4,5-c]pyridin-2-yl)pyrimidin-4-yl]amino]-5-(1-hydroxy-1-methyl-ethyl)cyclopentane-1,2-diol | 1332380-87-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1R,2S,3R,5S)-3-[[2-[cyclopropylmethyl(methyl)amino]-6-methyl-5-(4-methylthiazolo[4,5-c]pyridin-2-yl)pyrimidin-4-yl]amino]-5-(1-hydroxy-1-methyl-ethyl)cyclopentane-1,2-diol
• 英文别名: (1R,2S,3R,5S)-3-[[2-[cyclopropylmethyl(methyl)amino]-6-methyl-5-(4-methyl-[1,3]thiazolo[4,5-c]pyridin-2-yl)pyrimidin-4-yl]amino]-5-(2-hydroxypropan-2-yl)cyclopentane-1,2-diol
• CAS: 1332380-87-6
• 化学式: C₂₅H₃₄N₆O₃S
• 分子量: 498.649
• InChiKey: MEPOBBUMLQAOKH-HDIOYNLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-[(3aS,4R,6S,6aR)-4-[(5-iodo-6-methyl-2-methylsulfanylpyrimidin-4-yl)amino]-2,2-dimethyl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]propan-2-ol 在 盐酸 、 copper(l) iodide 、 四(三苯基膦)钯 、 caesium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 (1R,2S,3R,5S)-3-[[2-[cyclopropylmethyl(methyl)amino]-6-methyl-5-(4-methylthiazolo[4,5-c]pyridin-2-yl)pyrimidin-4-yl]amino]-5-(1-hydroxy-1-methyl-ethyl)cyclopentane-1,2-diol
  参考文献：
  名称：

  Synthesis and SAR of geminal substitutions at the C5′ carbosugar position of pyrimidine-derived HCV inhibitors

  摘要：

  The installation of geminal substitution at the C5' position of the carbosugar in our pyrimidine-derived hepatitis C inhibitor series is reported. SAR studies around the C5' position led to the installation of the dimethyl group as the optimal functionality. An improved route was subsequently designed to access these substitutions. Expanded SAR at the C2 amino position led to the utilization of C2 ethers. These compounds exhibited good potency, high selectivity, and excellent plasma exposure and bioavailability in rodent as well as in higher species. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.08.111

文献信息

• SUBSTITUTED PYRIDINE AND PYRIMIDINE DERIVATIVES AND THEIR USE IN TREATING VIRAL INFECTIONS
  申请人：Arasappan Ashok

  公开号：US20140242027A1

  公开（公告）日：2014-08-28

  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
• Synthesis and SAR of geminal substitutions at the C5′ carbosugar position of pyrimidine-derived HCV inhibitors
  作者：Vishal A. Verma、Randall Rossman、Frank Bennett、Lei Chen、Stephen Gavalas、Vinay Girijavallabhan、Yuhua Huang、Seong-Heon Kim、Aneta Kosinski、Patrick Pinto、Razia Rizvi、Bandarpalle Shankar、Ling Tong、Francisco Velazquez、Srikanth Venkatraman、Joseph Kozlowski、Malcolm MacCoss、Cecil D. Kwong、Namita Bansal、Hollis S. Kezar、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、Ashok Arasappan

  DOI：10.1016/j.bmcl.2012.08.111

  日期：2012.11

  The installation of geminal substitution at the C5' position of the carbosugar in our pyrimidine-derived hepatitis C inhibitor series is reported. SAR studies around the C5' position led to the installation of the dimethyl group as the optimal functionality. An improved route was subsequently designed to access these substitutions. Expanded SAR at the C2 amino position led to the utilization of C2 ethers. These compounds exhibited good potency, high selectivity, and excellent plasma exposure and bioavailability in rodent as well as in higher species. (C) 2012 Elsevier Ltd. All rights reserved.