(1R,2S,3R,5R)-3-[[5-(4,6-dimethylthiazolo[4,5-c]pyridin-2-yl)-6-methyl-2-[[(1R)-1-[4-(trifluoromethoxy)phenyl]ethyl]amino]pyrimidin-4-yl]amino]-5-(hydroxymethyl)cyclopentane-1,2-diol | 1396367-58-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (1R,2S,3R,5R)-3-[[5-(4,6-dimethylthiazolo[4,5-c]pyridin-2-yl)-6-methyl-2-[[(1R)-1-[4-(trifluoromethoxy)phenyl]ethyl]amino]pyrimidin-4-yl]amino]-5-(hydroxymethyl)cyclopentane-1,2-diol
• 英文别名: (1R,2S,3R,5R)-3-[[5-(4,6-dimethyl-[1,3]thiazolo[4,5-c]pyridin-2-yl)-6-methyl-2-[[(1R)-1-[4-(trifluoromethoxy)phenyl]ethyl]amino]pyrimidin-4-yl]amino]-5-(hydroxymethyl)cyclopentane-1,2-diol
• CAS: 1396367-58-0
• 化学式: C₂₈H₃₁F₃N₆O₄S
• 分子量: 604.653
• InChiKey: PGHSPONUSHYXSY-PGVOTNSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  174
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  [(3aS,4R,6R,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]methanol 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 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 (1R,2S,3R,5R)-3-[[5-(4,6-dimethylthiazolo[4,5-c]pyridin-2-yl)-6-methyl-2-[[(1R)-1-[4-(trifluoromethoxy)phenyl]ethyl]amino]pyrimidin-4-yl]amino]-5-(hydroxymethyl)cyclopentane-1,2-diol
  参考文献：
  名称：

  Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors

  摘要：

  Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery of the more potent pyridothiazole analogues 3. The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R-1, R-2 or R-3 positions of the molecule (compound 3). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC50), PK parameters in all species studied, and cross genotype activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.099

文献信息

• Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors
  作者：Vinay M. Girijavallabhan、Carmen Alvarez、Frank Bennett、Lei Chen、Stephen Gavalas、Yuhua Huang、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、Namita Bansal、Jeremy L. Clark、Anita T. Fowler、Hollis S. Kezar、Jacob Valiyaveettil、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.2012.06.099

  日期：2012.9

  Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery of the more potent pyridothiazole analogues 3. The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R-1, R-2 or R-3 positions of the molecule (compound 3). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC50), PK parameters in all species studied, and cross genotype activity. (C) 2012 Elsevier Ltd. All rights reserved.