cyclopentyl N-[(2S)-1-[(2S,4R)-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-4-[2-(2,4-dimethoxyphenyl)-1,3-thiazol-4-yl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate | 1446747-11-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: cyclopentyl N-[(2S)-1-[(2S,4R)-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-4-[2-(2,4-dimethoxyphenyl)-1,3-thiazol-4-yl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
• CAS: 1446747-11-0
• 化学式: C₃₇H₄₉N₅O₉S₂
• 分子量: 771.956
• InChiKey: OADWDNZXNCLGPI-DZWIBZJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  53
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  219
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  methyl (1R,2S)-1-[[(2S,4R)-4-(2-bromoacetyl)-1-[(2S)-2-(cyclopentyloxycarbonylamino)-3,3-dimethylbutanoyl]pyrrolidine-2-carbonyl]amino]-2-ethenylcyclopropane-1-carboxylate 在 水 、 三乙胺 、 sodium hydroxide 、 lithium hexamethyldisilazane 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 cyclopentyl N-[(2S)-1-[(2S,4R)-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-4-[2-(2,4-dimethoxyphenyl)-1,3-thiazol-4-yl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
  参考文献：
  名称：

  Discovery of novel P2 substituted 4-biaryl proline inhibitors of hepatitis C virus NS3 serine protease

  摘要：

  Inhibitors of hepatitis C virus NS3 serine protease often incorporate a large P2 moiety to interact with the surface of the enzyme while shielding part of the catalytic triad. This feature is important in many inhibitors in order to have the necessary potency needed for efficacy. In this Letter we explore some new P2 motifs to further exploit this region of the enzyme. In a continuing effort to replace the often found 4-hydroxyproline P2 core found in the majority of inhibitors for this target, various directly attached aryl derivatives were evaluated. Of these, the 2,4-disubstituted thiazole core proved to be the most interesting. SAR around this motif has lead to compounds with K-i's in the high picomolar range and provided cellular potencies in the single digit nM range. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.046