(t-Butoxycarbonyl)-l-valyl-N-(1,1,1,2,2-pentafluoro-5-methyl-3-oxo-4-hexanyl)proline amide | 149951-78-0

• 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: (t-Butoxycarbonyl)-l-valyl-N-(1,1,1,2,2-pentafluoro-5-methyl-3-oxo-4-hexanyl)proline amide
• 英文别名: {(S)-2-Methyl-1-[(S)-2-(3,3,4,4,4-pentafluoro-1-isopropyl-2-oxo-butylcarbamoyl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid tert-butyl ester；tert-butyl N-[(2S)-3-methyl-1-oxo-1-[(2S)-2-[(5,5,6,6,6-pentafluoro-2-methyl-4-oxohexan-3-yl)carbamoyl]pyrrolidin-1-yl]butan-2-yl]carbamate
• CAS: 149951-78-0
• 化学式: C₂₂H₃₄F₅N₃O₅
• 分子量: 515.521
• InChiKey: LPPLYAFRXXVJEO-LWEDLAQUSA-N

物化性质

• 沸点：
  590.9±50.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (t-Butoxycarbonyl)-l-valyl-N-(1,1,1,2,2-pentafluoro-5-methyl-3-oxo-4-hexanyl)proline amide 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 以91%的产率得到N-L-valyl-N-<3,3,4,4,4-pentafluoro-1-(1-methylethyl)-2-oxobutyl>-L-prolinamide hydrochloride
  参考文献：
  名称：

  Inhibition of Human Neutrophil Elastase with Peptidyl Electrophilic Ketones. 2. Orally Active PG-Val-Pro-Val Pentafluoroethyl Ketones

  摘要：

  Valylprolylvalyl pentafluoroethyl ketones with different N-protecting groups were evaluated in vitro and in vivo as inhibitors of human neutrophil elastase (HNE). Several of these compounds were found to be orally active in HNE-induced rat and hamster lung hemorrhage models. The compound with 4-(4-morpholinylcarbonyl)benzoyl as the protecting group, 71 (MDL 101,146), was studied in greater detail. Hydration and epimerization studies were performed on 71 and related compounds in various media, including human blood serum. Highperformance liquid chromatography studies on a reversed-phase system as a measure of the Lipophilicity of 71. and related compounds revealed a small range of relative retention times wherein the orally active compounds fell. The K-i value determined for 71 vs HNE was 25 nM.

  DOI：

  10.1021/jm00052a013
• 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 N-甲基吗啉 、 methyllithium lithium bromide 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 1.83h， 生成 (t-Butoxycarbonyl)-l-valyl-N-(1,1,1,2,2-pentafluoro-5-methyl-3-oxo-4-hexanyl)proline amide
  参考文献：
  名称：

  肽基全氟烷基酮的便捷合成

  摘要：

  描述了一种通过相应肽酯的直接亲核全氟烷基化制备α-氨基全氟烷基酮的简便方法。该方法用于由相应的N -Boc保护的脱氢缬氨酸甲酯3制备脱氢缬氨酸五氟乙基酮2。类似α氨基酯，Ñ -Boc缬氨酸甲酯4，将Boc-缬氨酰脯氨酰基dehydrovaline甲酯8A和Boc-缬氨酰脯氨酰-缬氨酸甲酯8b中也直接转化为相应的酮五氟乙基6，图9a和9b中。该方法还适用于由它们相应的酯合成七氟丙基和九氟丁基肽基酮11a和11b，尽管产率较低。这些氨基酮可用作制备肽基全氟烷基酮的中间体，已证明是人嗜中性粒细胞弹性蛋白酶的有效抑制剂。

  DOI：

  10.1016/s0022-1139(97)00154-1

文献信息

• PERFLUOROALKYL KETONE INHIBITORS OF ELASTASE AND PROCESSES FOR MAKING THE SAME
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0763055B1

  公开（公告）日：1999-11-03
• US6008196A
  申请人：——

  公开号：US6008196A

  公开（公告）日：1999-12-28
• US6265381B1
  申请人：——

  公开号：US6265381B1

  公开（公告）日：2001-07-24
• [EN] PERFLUOROALKYL KETONE INHIBITORS OF ELASTASE AND PROCESSES FOR MAKING THE SAME<br/>[FR] INHIBITEURS D'ELASTASE AU PERFLUOROALKYLE CETONE ET PROCEDES DE PRODUCTION ASSOCIES
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：WO1995033762A1

  公开（公告）日：1995-12-14

  (EN) This invention relates to compounds which are inhibitors of elastase, particularly human neutrophil elastase, and to novel processes for making the same. As inhibitors of human neutrophil elastase, the compounds are useful in the treatment of a patient afflicted with a neutrophil associated inflammatory disease.(FR) Cette invention concerne des composés qui inhibent l'élastase, notamment l'élastase des polynucléaires neutrophiles humains, et de nouveaux procédés de production de ces inhibiteurs. Ces composés sont utiles comme inhibiteurs de l'élastase des polynucléaires neutrophiles humains dans le traitement d'un patient atteint d'une maladie inflammatoire associée aux polynucléaires neutrophiles.
• A convenient synthesis of peptidyl perfluoroalkyl ketones
  作者：Robert J. Cregge、Timothy T. Curran、William A. Metz

  DOI：10.1016/s0022-1139(97)00154-1

  日期：1998.2

  converted directly to the corresponding pentafluoroethyl ketones 6, 9a and 9b. The method was also applied to the synthesis of heptafluoropropyl- and nonafluorobutyl peptidyl ketones 11a and 11b from their corresponding esters, albeit in lower yield. These amino ketones are useful as intermediates in the preparation of peptidyl perfluoroalkyl ketones which have been shown to be potent inhibitors of human

  描述了一种通过相应肽酯的直接亲核全氟烷基化制备α-氨基全氟烷基酮的简便方法。该方法用于由相应的N -Boc保护的脱氢缬氨酸甲酯3制备脱氢缬氨酸五氟乙基酮2。类似α氨基酯，Ñ -Boc缬氨酸甲酯4，将Boc-缬氨酰脯氨酰基dehydrovaline甲酯8A和Boc-缬氨酰脯氨酰-缬氨酸甲酯8b中也直接转化为相应的酮五氟乙基6，图9a和9b中。该方法还适用于由它们相应的酯合成七氟丙基和九氟丁基肽基酮11a和11b，尽管产率较低。这些氨基酮可用作制备肽基全氟烷基酮的中间体，已证明是人嗜中性粒细胞弹性蛋白酶的有效抑制剂。