(16aS,17aR,17bS)-13(S)-[[[(1(S)-cyclohexyl-2-cyclopropyl-2-oxoethyl)amino]carbonyl]amino]hexadecahydro-17,17-dimethyl-α,1,14-trioxo-N-(2-propenyl)-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1,5,8]oxadiazacyclohexadecine-3(S)-acetamide | 848775-91-7

• 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: (16aS,17aR,17bS)-13(S)-[[[(1(S)-cyclohexyl-2-cyclopropyl-2-oxoethyl)amino]carbonyl]amino]hexadecahydro-17,17-dimethyl-α,1,14-trioxo-N-(2-propenyl)-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1,5,8]oxadiazacyclohexadecine-3(S)-acetamide
• 英文别名: 2-[(3S,13S,16S,17R,19S)-3-({[(1S)-1-cyclohexyl-2-cyclopropyl-2-oxoethyl]carbamoyl}amino)-18,18-dimethyl-2,15-dioxo-5-oxa-1,14-diazatricyclo[14.4.0.0^{17,19}]icosan-13-yl]-2-oxo-N-(prop-2-en-1-yl)acetamide；2-[(3S,13S,16S,17R,19S)-3-[[(1S)-1-cyclohexyl-2-cyclopropyl-2-oxoethyl]carbamoylamino]-18,18-dimethyl-2,15-dioxo-5-oxa-1,14-diazatricyclo[14.4.0.017,19]icosan-13-yl]-2-oxo-N-prop-2-enylacetamide
• CAS: 848775-91-7
• 化学式: C₃₆H₅₅N₅O₇
• 分子量: 669.862
• InChiKey: JLQJJGKYIDWNPK-AQRCPPRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  48
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2S)-2-cyclohexyl-1-cyclopropyl-2-isocyanatoethanone 、 N-allyl-2-((3S,13S,16aS,17aR,17bS)-13-amino-17,17-dimethyl-1,14-dioxohexadecahydro-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1]oxa[5,8]diazacyclohexadecin-3-yl)-2-oxoacetamide hydrochloride 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 以34 mg的产率得到(16aS,17aR,17bS)-13(S)-[[[(1(S)-cyclohexyl-2-cyclopropyl-2-oxoethyl)amino]carbonyl]amino]hexadecahydro-17,17-dimethyl-α,1,14-trioxo-N-(2-propenyl)-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1,5,8]oxadiazacyclohexadecine-3(S)-acetamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Oxygen-Containing Macrocyclic Peptidomimetics as Inhibitors of HCV NS3 Protease

  摘要：

  HCV infection is considered a silent epidemic because most people infected do not develop acute symptoms. Instead, the disease progresses to a chronic state leading to cirrhosis and hepatocarcinoma. Novel therapies are needed to combat this major health threat. The HCV NS3 serine protease has been the target of continuous investigation because of its pivotal role in viral replication. Herein, we present the P1-P3 macrocyclization approach followed for identification of HCV NS3 inhibitors as potential back-up candidates to our first generation drug candidate, Sch 503034 (1). Different P1-P3 linkers were investigated to identify novel macrocyclic scaffolds. SAR exploration of P3-caps in the macrocyclic cores allowed the identification of L-serine derived macrocycle 32 (K-i* = 3 nM, EC90 = 30 nM) and allo-threonine derived macrocycle 36 (K-i* = 3 nM, EC90 = 30 nM) as potent HCV NS3 protease inhibitors.

  DOI：

  10.1021/jm801201u

文献信息

• MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE
  申请人：Schering Corporation

  公开号：EP1664092B1

  公开（公告）日：2011-02-02
• US7592419B2
  申请人：——

  公开号：US7592419B2

  公开（公告）日：2009-09-22
• Design, Synthesis, and Evaluation of Oxygen-Containing Macrocyclic Peptidomimetics as Inhibitors of HCV NS3 Protease
  作者：Francisco Velázquez、Srikanth Venkatraman、Melissa Blackman、Patrick Pinto、Stéphane Bogen、Mousumi Sannigrahi、Kevin Chen、John Pichardo、Andrea Hart、Xiao Tong、Viyyoor Girijavallabhan、F. George Njoroge

  DOI：10.1021/jm801201u

  日期：2009.2.12

  HCV infection is considered a silent epidemic because most people infected do not develop acute symptoms. Instead, the disease progresses to a chronic state leading to cirrhosis and hepatocarcinoma. Novel therapies are needed to combat this major health threat. The HCV NS3 serine protease has been the target of continuous investigation because of its pivotal role in viral replication. Herein, we present the P1-P3 macrocyclization approach followed for identification of HCV NS3 inhibitors as potential back-up candidates to our first generation drug candidate, Sch 503034 (1). Different P1-P3 linkers were investigated to identify novel macrocyclic scaffolds. SAR exploration of P3-caps in the macrocyclic cores allowed the identification of L-serine derived macrocycle 32 (K-i* = 3 nM, EC90 = 30 nM) and allo-threonine derived macrocycle 36 (K-i* = 3 nM, EC90 = 30 nM) as potent HCV NS3 protease inhibitors.