(1aS,13R,14aS,19aR,Z)-13-((8-bromo-7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)-1,1a,4,5,6,7,8,9,12,13,14,14a-dodecahydro-10H,15H,17H,19H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclopentadecine-10,15,17,19-tetraone | 1079097-87-2

• 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: (1aS,13R,14aS,19aR,Z)-13-((8-bromo-7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)-1,1a,4,5,6,7,8,9,12,13,14,14a-dodecahydro-10H,15H,17H,19H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclopentadecine-10,15,17,19-tetraone
• CAS: 1079097-87-2
• 化学式: C₃₂H₃₁BrN₄O₇S
• 分子量: 695.591
• InChiKey: MPQXZLGFHQHSGZ-RGWOCJCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  45.0
• 可旋转键数：
  4.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  128.23
• 氢给体数：
  0.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  环丙磺酰胺 、 (1aS,13R,14aS,19aR,Z)-13-((8-bromo-7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)-1,1a,4,5,6,7,8,9,12,13,14,14a-dodecahydro-10H,15H,17H,19H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclopentadecine-10,15,17,19-tetraone 在 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 (1S,4R,6S,7Z,18R)-18-[8-bromo-7-methoxy-2-(1,3-thiazol-2-yl)quinolin-4-yl]oxy-N-cyclopropylsulfonyl-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxamide
  参考文献：
  名称：

  Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine protease inhibitors

  摘要：

  Starting from the previously reported HCV NS3/4A protease inhibitor BILN 2061 (1), we have used a fast-follower approach to identify a novel series of HCV NS3/4A protease inhibitors in which (i) the P3 amino moiety and its capping group have been truncated, (ii) a sulfonamide is introduced in the P1 cyclopropyl amino acid, (iii) the position 8 of the quinoline is substituted with a methyl or halo group, and (iv) the ring size of the macrocycle has been reduced to 14 atoms. SAR analysis performed with a limited set of compounds led to the identification of N-{17-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin4-yloxy]-2,14-dioxo-3,15-diazatricyclo [13.3.0.0 [Bartenschlager, R.; Lohmann, V. J. Gen. Virol. 2000, 81, 1631; Vincent Soriano, Antonio Madejon, Eugenia Vispo, Pablo Labarga, Javier Garcia-Samaniego, Luz Martin-Carbonero, Julie Sheldon, Marcelle Bottecchia, Paula Tuma, Pablo Barreiro Expert Opin. Emerg. Drugs, 2008, 13, 1-19]]octadec-7-ene-4-carbonyl}(1-methylcyclopropyl)(1-methylcyclopropyl) sulfonamide 19l an extremely potent (K-i = 0.20 nM, EC50 = 3.7 nM), selective, and orally bioavailable dipeptide NS3/4A protease inhibitor, which has features attractive for further preclinical development. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.124
• 作为产物：
  描述：

  (1S,4R,6S,7Z,18R)-18-[8-bromo-7-methoxy-2-(1,3-thiazol-2-yl)quinolin-4-yl]oxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid 、 N,N'-羰基二咪唑 以 四氢呋喃 为溶剂， 生成 (1aS,13R,14aS,19aR,Z)-13-((8-bromo-7-methoxy-2-(thiazol-2-yl)quinolin-4-yl)oxy)-1,1a,4,5,6,7,8,9,12,13,14,14a-dodecahydro-10H,15H,17H,19H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclopentadecine-10,15,17,19-tetraone
  参考文献：
  名称：

  Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine protease inhibitors

  摘要：

  Starting from the previously reported HCV NS3/4A protease inhibitor BILN 2061 (1), we have used a fast-follower approach to identify a novel series of HCV NS3/4A protease inhibitors in which (i) the P3 amino moiety and its capping group have been truncated, (ii) a sulfonamide is introduced in the P1 cyclopropyl amino acid, (iii) the position 8 of the quinoline is substituted with a methyl or halo group, and (iv) the ring size of the macrocycle has been reduced to 14 atoms. SAR analysis performed with a limited set of compounds led to the identification of N-{17-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin4-yloxy]-2,14-dioxo-3,15-diazatricyclo [13.3.0.0 [Bartenschlager, R.; Lohmann, V. J. Gen. Virol. 2000, 81, 1631; Vincent Soriano, Antonio Madejon, Eugenia Vispo, Pablo Labarga, Javier Garcia-Samaniego, Luz Martin-Carbonero, Julie Sheldon, Marcelle Bottecchia, Paula Tuma, Pablo Barreiro Expert Opin. Emerg. Drugs, 2008, 13, 1-19]]octadec-7-ene-4-carbonyl}(1-methylcyclopropyl)(1-methylcyclopropyl) sulfonamide 19l an extremely potent (K-i = 0.20 nM, EC50 = 3.7 nM), selective, and orally bioavailable dipeptide NS3/4A protease inhibitor, which has features attractive for further preclinical development. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.124