(4R,6S,15S,17S)-17-[8-chloro-7-methoxy-2-(4-methyl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-13-methyl-2,14-dioxo-1,3,13-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (4R,6S,15S,17S)-17-[8-chloro-7-methoxy-2-(4-methyl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-13-methyl-2,14-dioxo-1,3,13-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid
• 化学式: C₃₁H₃₄ClN₅O₆S
• 分子量: 640.16
• InChiKey: AZUQQQDJASRPCW-URETUEOVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  44
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  162
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  环丙磺酰胺 、 (4R,6S,15S,17S)-17-[8-chloro-7-methoxy-2-(4-methyl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-13-methyl-2,14-dioxo-1,3,13-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid 反应 2.33h， 生成 (4R,6S,15S,17S)-17-[8-chloro-7-methoxy-2-(4-methyl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-N-cyclopropylsulfonyl-13-methyl-2,14-dioxo-1,3,13-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxamide
  参考文献：
  名称：

  Discovery and structural diversity of the hepatitis C virus NS3/4A serine protease inhibitor series leading to clinical candidate IDX320

  摘要：

  Exploration of the P2 region by mimicking the proline motif found in BILN2061 resulted in the discovery of two series of potent HCV NS3/4A protease inhibitors. X-ray crystal structure of the ligand in contact with the NS3/4A protein and modulation of the quinoline heterocyclic region by structure based design and modeling allowed for the optimization of enzyme potency and cellular activity. This research led to the selection of clinical candidate IDX320 having good genotype coverage and pharmacokinetic properties in various species. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.009
• 作为产物：
  描述：

  2,8-dichloro-7-methoxy-4-(4-methoxybenzyloxy)quinoline 在 bis-triphenylphosphine-palladium(II) chloride 、 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.17h， 生成 (4R,6S,15S,17S)-17-[8-chloro-7-methoxy-2-(4-methyl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-13-methyl-2,14-dioxo-1,3,13-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid
  参考文献：
  名称：

  Discovery and structural diversity of the hepatitis C virus NS3/4A serine protease inhibitor series leading to clinical candidate IDX320

  摘要：

  Exploration of the P2 region by mimicking the proline motif found in BILN2061 resulted in the discovery of two series of potent HCV NS3/4A protease inhibitors. X-ray crystal structure of the ligand in contact with the NS3/4A protein and modulation of the quinoline heterocyclic region by structure based design and modeling allowed for the optimization of enzyme potency and cellular activity. This research led to the selection of clinical candidate IDX320 having good genotype coverage and pharmacokinetic properties in various species. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.009

文献信息

• Discovery and structural diversity of the hepatitis C virus NS3/4A serine protease inhibitor series leading to clinical candidate IDX320
  作者：Christophe C. Parsy、François-René Alexandre、Valérie Bidau、Florence Bonnaterre、Guillaume Brandt、Catherine Caillet、Sylvie Cappelle、Dominique Chaves、Thierry Convard、Michel Derock、Damien Gloux、Yann Griffon、Lisa B. Lallos、Frederic Leroy、Michel Liuzzi、Anna-Giulia Loi、Laure Moulat、Musiu Chiara、Houcine Rahali、Virginie Roques、Elodie Rosinovsky、Simon Savin、Maria Seifer、David Standring、Dominique Surleraux

  DOI：10.1016/j.bmcl.2015.09.009

  日期：2015.11

  Exploration of the P2 region by mimicking the proline motif found in BILN2061 resulted in the discovery of two series of potent HCV NS3/4A protease inhibitors. X-ray crystal structure of the ligand in contact with the NS3/4A protein and modulation of the quinoline heterocyclic region by structure based design and modeling allowed for the optimization of enzyme potency and cellular activity. This research led to the selection of clinical candidate IDX320 having good genotype coverage and pharmacokinetic properties in various species. (C) 2015 Elsevier Ltd. All rights reserved.