(1aS,12R,13aS,18aR,Z)-12-((8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yl)oxy)-1a,4,5,6,7,8,11,12,13,13a-decahydro-14H,16H,18H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclotetradecine-9,14,16,18(1H)-tetraone | 1079097-92-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: (1aS,12R,13aS,18aR,Z)-12-((8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yl)oxy)-1a,4,5,6,7,8,11,12,13,13a-decahydro-14H,16H,18H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclotetradecine-9,14,16,18(1H)-tetraone
• CAS: 1079097-92-9
• 化学式: C₃₄H₃₅ClN₄O₇S
• 分子量: 679.193
• InChiKey: JWXFJULKIOSWKC-KUWGUDSOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.28
• 重原子数：
  47.0
• 可旋转键数：
  5.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  1-甲基环丙烷磺酰胺 、 (1aS,12R,13aS,18aR,Z)-12-((8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yl)oxy)-1a,4,5,6,7,8,11,12,13,13a-decahydro-14H,16H,18H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclotetradecine-9,14,16,18(1H)-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 N-{17-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-2,14-dioxo-3,15-diazatricyclo[13.3.0.0^4,6]octadec-7-ene-4-carbonyl}-(1-methylcyclopropyl)sulfonamide
  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,17R)-17-[8-chloro-7-methoxy-2-(4-propan-2-yl-1,3-thiazol-2-yl)quinolin-4-yl]oxy-2,14-dioxo-3,15-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carboxylic acid 、 N,N'-羰基二咪唑 以 四氢呋喃 为溶剂， 生成 (1aS,12R,13aS,18aR,Z)-12-((8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yl)oxy)-1a,4,5,6,7,8,11,12,13,13a-decahydro-14H,16H,18H-cyclopropa[e]oxazolo[3,4-d]pyrrolo[1,2-a][1,4]diazacyclotetradecine-9,14,16,18(1H)-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