methyl (4R,6S,9S,16E)-9-tert-butyl-2,8,11-trioxo-3,12-dioxa-1,7,10-triazatetracyclo[16.6.2.1(4,7).0(22,26)]heptacosa-16,18(26),19,21-tetraene-6-carboxylate | 1216962-31-0

• 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: methyl (4R,6S,9S,16E)-9-tert-butyl-2,8,11-trioxo-3,12-dioxa-1,7,10-triazatetracyclo[16.6.2.1(4,7).0(22,26)]heptacosa-16,18(26),19,21-tetraene-6-carboxylate
• 英文别名: methyl (4R,6S,9S,16E)-9-tert-butyl-2,8,11-trioxo-3,12-dioxa-1,7,10-triazatetracyclo[16.6.2.14,7.022,26]heptacosa-16,18,20,22(26)-tetraene-6-carboxylate
• CAS: 1216962-31-0
• 化学式: C₂₈H₃₇N₃O₇
• 分子量: 527.618
• InChiKey: VASBRIMPDPCWDQ-NXNFGYDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  38
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (4R,6S,9S,16E)-9-tert-butyl-2,8,11-trioxo-3,12-dioxa-1,7,10-triazatetracyclo[16.6.2.1(4,7).0(22,26)]heptacosa-16,18(26),19,21-tetraene-6-carboxylate 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  Discovery of Vaniprevir (MK-7009), a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor

  摘要：

  A new class of H CV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the PI side chain of this class of compounds via a modular synthetic strategy allowed for the optimization of enzyme potency, cellular activity, and rat liver exposure following oral closing. These studies led to the identification of clinical candidate 35b (vaniprevir, MK-7009), which is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species.

  DOI：

  10.1021/jm9015526
• 作为产物：
  描述：

  methyl 3-methyl-N-[(pent-4-en-1-yloxy)carbonyl]-L-valyl-(4R)-4-{[(8-vinyl-3,4-dihydroisoquinolin-2(1H)-yl)carbonyl]oxy}-L-prolinate 在 詹氏催化剂 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.0h， 以82%的产率得到methyl (4R,6S,9S,16E)-9-tert-butyl-2,8,11-trioxo-3,12-dioxa-1,7,10-triazatetracyclo[16.6.2.1(4,7).0(22,26)]heptacosa-16,18(26),19,21-tetraene-6-carboxylate
  参考文献：
  名称：

  Discovery of Vaniprevir (MK-7009), a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor

  摘要：

  A new class of H CV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the PI side chain of this class of compounds via a modular synthetic strategy allowed for the optimization of enzyme potency, cellular activity, and rat liver exposure following oral closing. These studies led to the identification of clinical candidate 35b (vaniprevir, MK-7009), which is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species.

  DOI：

  10.1021/jm9015526

文献信息

• Discovery of Vaniprevir (MK-7009), a Macrocyclic Hepatitis C Virus NS3/4a Protease Inhibitor
  作者：John A. McCauley、Charles J. McIntyre、Michael T. Rudd、Kevin T. Nguyen、Joseph J. Romano、John W. Butcher、Kevin F. Gilbert、Kimberly J. Bush、M. Katharine Holloway、John Swestock、Bang-Lin Wan、Steven S. Carroll、Jillian M. DiMuzio、Donald J. Graham、Steven W. Ludmerer、Shi-Shan Mao、Mark W. Stahlhut、Christine M. Fandozzi、Nicole Trainor、David B. Olsen、Joseph P. Vacca、Nigel J. Liverton

  DOI：10.1021/jm9015526

  日期：2010.3.25

  A new class of H CV NS3/4a protease inhibitors which contain a P2 to P4 macrocyclic constraint was designed using a molecular-modeling derived strategy. Exploration of the P2 heterocyclic region, the P2 to P4 linker, and the PI side chain of this class of compounds via a modular synthetic strategy allowed for the optimization of enzyme potency, cellular activity, and rat liver exposure following oral closing. These studies led to the identification of clinical candidate 35b (vaniprevir, MK-7009), which is active against both the genotype 1 and genotype 2 NS3/4a protease enzymes and has good plasma exposure and excellent liver exposure in multiple species.