3-tert-Butoxycarbonylamino-5,5-difluoro-2-hydroxy-pentanoic acid | 669063-39-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 3-tert-Butoxycarbonylamino-5,5-difluoro-2-hydroxy-pentanoic acid
• CAS: 669063-39-2
• 化学式: C₁₀H₁₇F₂NO₅
• 分子量: 269.245
• InChiKey: IVMNWZKDYZFQOR-UHFFFAOYSA-N

反应信息

• 作为反应物：
  描述：

  3-tert-Butoxycarbonylamino-5,5-difluoro-2-hydroxy-pentanoic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 生成 3-Amino-5,5-difluoro-2-hydroxy-pentanoic acid ((S)-1-phenyl-ethyl)-amide; compound with trifluoro-acetic acid
  参考文献：
  名称：

  P1 and P3 optimization of novel bicycloproline P2 bearing tetrapeptidyl α-ketoamide based HCV protease inhibitors

  摘要：

  With the aim of discovering potent and selective HCV protease inhibitors, we synthesized and evaluated a series of Ia based tetrapeptidyl ketoamides with additional modification(s) at P1', P1, and P3 positions. As a result of this effort, we found that replacement of the P3 valine with tert-leucine resulted in the discovery of a series of inhibitors (e.g., 3a, 3c, and 4c) endowed with improved enzyme and/or cellular activity relative to Ia. When dosed to F-344 rats orally at 50 mg/kg, 3a achieved 2.5 x higher liver and plasma exposure in comparison to that detected with 1a. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.075
• 作为产物：
  描述：

  [2-Cyano-1-(2,2-difluoro-ethyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 3-tert-Butoxycarbonylamino-5,5-difluoro-2-hydroxy-pentanoic acid
  参考文献：
  名称：

  A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease

  摘要：

  The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P-1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K-i 30 nM) and reversible covalent inhibitors (6, K-i 0.5 nM; and 8 K-i* 10 pM). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00842-3

文献信息

• Inhibitors of hepatitis C virus NS3/4A: α-Ketoamide based macrocyclic inhibitors
  作者：Salvatore Avolio、Keith Robertson、Josè Ignacio Martin Hernando、Jillian DiMuzio、Vincenzo Summa

  DOI：10.1016/j.bmcl.2009.02.079

  日期：2009.4

  A novel series of hepatitis C virus (HCV) NS3/4A protease inhibitors bearing a P2-P4 macrocycle and a P1-P1' alpha-ketoamide serine trap is reported. The NS3 protease, which is essential for viral replication, is considered one of the most attractive targets for developing novel anti-HCV therapies. The optimization of both the macrocycle and the warhead portions led to the discovery of compounds 8b and 8g with a good activity both in the enzyme as well as in the cell based (replicon) assays with favorable PK profile in a preclinical species. (c) 2009 Elsevier Ltd. All rights reserved.