(1S,4R,6S,17R)-17-(7-methoxy-2-phenylquinolin-4-yl)oxy-2,14-dioxo-3,13,15-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid | 862120-33-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (1S,4R,6S,17R)-17-(7-methoxy-2-phenylquinolin-4-yl)oxy-2,14-dioxo-3,13,15-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid
• CAS: 862120-33-0
• 化学式: C₃₂H₃₄N₄O₆
• 分子量: 570.645
• InChiKey: NZRAEQDAIGTDJY-FMSVZYFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  42
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  环丙磺酰胺 、 (1S,4R,6S,17R)-17-(7-methoxy-2-phenylquinolin-4-yl)oxy-2,14-dioxo-3,13,15-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid 在 N,N'-羰基二咪唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors

  摘要：

  A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (K-i = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 mu M) inhibitor, displaying an excellent PK pro. le in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.004
• 作为产物：
  描述：

  ethyl (1S,4R,6S,17R)-17-(7-methoxy-2-phenylquinolin-4-yl)oxy-2,14-dioxo-3,13,15-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylate 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 48.0h， 生成 (1S,4R,6S,17R)-17-(7-methoxy-2-phenylquinolin-4-yl)oxy-2,14-dioxo-3,13,15-triazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid
  参考文献：
  名称：

  Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors

  摘要：

  A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (K-i = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 mu M) inhibitor, displaying an excellent PK pro. le in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.004

文献信息

• Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors
  作者：Sandrine Vendeville、Magnus Nilsson、Herman de Kock、Tse-I Lin、Dmitry Antonov、Björn Classon、Susana Ayesa、Vladimir Ivanov、Per-Ola Johansson、Pia Kahnberg、Anders Eneroth、Kristina Wikstrom、Lotta Vrang、Michael Edlund、Stefan Lindström、Wim Van de Vreken、David McGowan、Abdellah Tahri、Lili Hu、Oliver Lenz、Frederic Delouvroy、Marleen Van Dooren、Natalie Kindermans、Dominique Surleraux、Piet Wigerinck、Åsa Rosenquist、Bertil Samuelsson、Kenneth Simmen、Pierre Raboisson

  DOI：10.1016/j.bmcl.2008.10.004

  日期：2008.12

  A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (K-i = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 mu M) inhibitor, displaying an excellent PK pro. le in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration. (C) 2008 Elsevier Ltd. All rights reserved.