tert-butoxycarbonyl-L-valyl-N-(1-benzyl-3,3,3-trifluoro-2-oxopropyl)-L-prolinamide | 208593-74-2

• 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: tert-butoxycarbonyl-L-valyl-N-(1-benzyl-3,3,3-trifluoro-2-oxopropyl)-L-prolinamide
• 英文别名: {1-[2-(1-Benzyl-3,3,3-trifluoro-2-oxo-propylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-3-methyl-1-oxo-1-[(2S)-2-[(4,4,4-trifluoro-3-oxo-1-phenylbutan-2-yl)carbamoyl]pyrrolidin-1-yl]butan-2-yl]carbamate
• CAS: 208593-74-2
• 化学式: C₂₅H₃₄F₃N₃O₅
• 分子量: 513.557
• InChiKey: RQBJCPKLQFRGBI-MNNMKWMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butoxycarbonyl-L-valyl-N-(1-benzyl-3,3,3-trifluoro-2-oxopropyl)-L-prolinamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以94%的产率得到L-valyl-N-(1-benzyl-3,3,3-trifluoro-2-oxopropyl)-L-prolinamide
  参考文献：
  名称：

  Non-Peptidic inhibitors of human chymase. Synthesis, structure–activity relationships, and pharmacokinetic profiles of a series of 5-amino-6-oxo-1,6-dihydropyrimidine-containing trifluoromethyl ketones

  摘要：

  Chymase possesses a wide variety of actions, including promotion of angiotensin II production and histamine release from mast cells. However, due to a lack of effective inhibitors featuring both high inhibitory activity and high metabolic stability, the pathophysiological role of chymase has not been fully elucidated. We designed non-peptidic inhibitors based on the predicted binding mode of the peptidic chymase inhibitor Val-Pro-Phe-CF3 and demonstrated that the Val-Pro unit is replaceable with a (5-amino-6-oxo-2-phenyl-1,6-dihydro-1-pyrimidinyl)acetyl moiety. Structure-activity relationship studies revealed that phenyl substitution at the 2-position of the pyrimidinone ring is indispensable for high activity. The most potent compound 1h (K-i = 0.0506 muM) is superior in potency to the parent peptidic inhibitor Val-Pro-Phe-CF3 and has good selectivity for chymase over other proteases. The related analogue 1e was orally absorbed and maintained high plasma levels for at least 2 h. These results suggest that the derivatives reported here could be developed as agents for treatment of chymase-induced disease. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00244-3
• 作为产物：
  描述：

  N-[(1,1-二甲基乙氧基)羰基]-L-缬氨酰-L-脯氨酸 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 戴斯-马丁氧化剂 、 三乙胺 作用下， 生成 tert-butoxycarbonyl-L-valyl-N-(1-benzyl-3,3,3-trifluoro-2-oxopropyl)-L-prolinamide
  参考文献：
  名称：

  Peptidyl human heart chymase inhibitors. 1. Synthesis and inhibitory activity of difluoromethylene ketone derivatives bearing P′ binding subsites

  摘要：

  Peptidyl difluoromethylene ketone derivatives were designed to take advantage of probable additional interactions with the S' subsite of human heart chymase. They showed potent inhibitory activities against human heart chymase and were more efficient than bovine chymotrypsin. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00131-0