ICI 200880 | 105080-50-0

• 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: ICI 200880
• 英文别名: 4-(4-chlorophenyl sulfonylcarbamoyl)benzoyl-L-valyl-L-prolyl-1-(RS)-(1-trifluoroacetyl-2-methylprolyl)amide；ICI-200,880；N-[4-[(4-Chlorophenyl)sulfonylaminocarbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide；4-N-(4-chlorophenyl)sulfonyl-1-N-[(2S)-3-methyl-1-oxo-1-[(2S)-2-[(1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl]pyrrolidin-1-yl]butan-2-yl]benzene-1,4-dicarboxamide
• CAS: 105080-50-0
• 化学式: C₃₀H₃₄ClF₃N₄O₇S
• 分子量: 687.137
• InChiKey: YGPYJEFIYYPEEE-OTKIHZFJSA-N

物化性质

• 密度：
  1.361±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  167
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ICI 200880 在 乙酸酐 、 溶剂黄146 作用下， 以 乙酸乙酯 为溶剂， 以49%的产率得到(E)-N-<4-<<<(4-chlorophenyl)sulfonyl>amino>carbonyl>benzoyl>-L-valyl-N-<2-(acetyloxy)-3,3,3-trifluoro-1-(1-methylethyl)-1-propenyl>-L-prolinamide
  参考文献：
  名称：

  Acylated enol derivatives as prodrugs of elastase inhibitors

  摘要：

  这项发明涉及已知弹性蛋白酶抑制剂的酰化烯醇衍生物。这些化合物在治疗各种炎症性疾病，包括囊性纤维化和肺气肿，或作为治疗这些疾病的有效化合物的前药方面是有用的。

  公开号：

  US05698523A1
• 作为产物：
  描述：

  、 N-L-valyl-N-<3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl>-L-prolinamide hydrochloride 在 N-甲基吗啉 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 ICI 200880
  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

文献信息

• Inhibition of Human Neutrophil Elastase. 3. An Orally Active Enol Acetate Prodrug
  作者：Joseph P. Burkhart、Jack R. Koehl、Shujaath Mehdi、Sherrie L. Durham、Michael J. Janusz、Edward W. Huber、Michael R. Angelastro、Shyam Sunder、William A. Metz

  DOI：10.1021/jm00002a003

  日期：1995.1

  vitro studies, in the presence of added esterase, and 19F NMR studies, in biological media, indicated that the E-enol acetate derivatives should act as prodrugs in vivo. The ED50 value for (E)-N-[4-(4-morpholinylcarbonyl)benzoyl]-L-valyl-N-[2- (acetyloxy)-3,3,4,4,4-pentafluoro-1-(1-methylethyl)-1-buteny l]-L-prolinamide (20), when administered orally in the hamster lung hemorrhage model, was 9 mg/kg

  N- [4-（4-吗啉基羰基）苯甲酰基] -L-戊基-N- [3,3,4,4,4-戊五氟-1-（1-甲基乙基）-2-氧丁基] -L的几种类似物合成了其中已消除了P1残基手性中心的β-脯氨酰胺（1），并作为人嗜中性粒细胞弹性蛋白酶（HNE）的抑制剂进行了测试。在这项工作的过程中观察到的结果导致开发了一种从HNE抑制剂（在P1处含有差向异构体的混合物）一步一步，立体选择性地合成E-烯醇乙酸酯衍生物的方法。在存在酯酶的情况下进行的体外研究以及在生物介质中的19 F NMR研究表明，乙酸烯醇酯衍生物应在体内充当前药。（E）-N- [4-（4-吗啉基羰基）苯甲酰基] -L-戊基-N- [2-（乙酰氧基）-3,3,4,4,4-五氟-1-（1）的ED50值-甲基乙基）-1-丁烯基1] -L-脯氨酰胺（20），
• 4-(4-Chlorophenylsulphonylcarbamoyl)benzoyl-L-valyl-L-proline-1-(RS)-(1-trifluoroacetyl-2-methylpropyl)amide for treating haemorrhage associated with acute non-lymphocytic leukaemia
  申请人：ZENECA LIMITED

  公开号：EP0463811A3

  公开（公告）日：1992-04-01

  The invention includes a novel therapeutic agent comprising 4-(4-chlorophenylsulphonylcarbamoyl)benzoyl-L-valyl-L-proline 1(RS)-(1-trifluoroacetyl-2methylpropyl)amide for use in the prevention or treatment of haemorrhagic conditions associated with acute non-lymphocytic leukaemia or its therapy, the use of this peptide derivative in the manufacture of a medicament for the prevention or treatment of said haemorrhagic conditions, as well as a method of prevention or treatment of said haemorrhagic conditions, as well as a method of prevention or treatment of said haemorrhagic conditions using the peptide derivative.

  本发明包括一种新型治疗剂，该治疗剂包含 4-(4-氯苯基磺酰氨基甲酰基)苯甲酰-L-缬氨酰-L-脯氨酸 1(RS)-(1-三氟乙酰基-2-甲基丙基)酰胺，用于预防或治疗与急性非淋巴细胞白血病或其治疗相关的出血性疾病、将该肽衍生物用于制造预防或治疗上述出血性疾病的药物，以及预防或治疗上述出血性疾病的方法，以及使用该肽衍生物预防或治疗上述出血性疾病的方法。
• MEYER, JOHN C.;SPREEN, RUSSELL C.;HALL, JAMES E., J. CHROMATOGR., 522,(1990) C. 213-226
  作者：MEYER, JOHN C.、SPREEN, RUSSELL C.、HALL, JAMES E.

  DOI：——

  日期：——
• Therapeutic agent for treatment and prevention of adult respiratory distress syndrome
  申请人：ZENECA LIMITED

  公开号：EP0458536B1

  公开（公告）日：1998-03-18
• USE OF 4-(4-CHLOROPHENYL-SULPHONYLCARBAMOYL) BENZOYL-L-VALYL-L-PROLINE 1($i(RS))-(1-TRIFLUOROACETYL-2-METHYLPROPYL) AMIDE IN THE TREATMENT OF VASCULAR DISEASES
  申请人：ZENECA LIMITED

  公开号：EP0589937A1

  公开（公告）日：1994-04-06