poststatin | 160866-54-6

• 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: poststatin
• 英文别名: (2S)-2-[[(2R)-2-[[3-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-2-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoic acid
• CAS: 160866-54-6
• 化学式: C₂₆H₄₇N₅O₇
• 分子量: 541.688
• InChiKey: LRXVQHCIMZSTJH-AIPWLVHISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  197
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  苯丁酸,酸酐 、 poststatin 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以83%的产率得到(2S)-3-methyl-2-[[(2R)-4-methyl-2-[[3-[[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(4-phenylbutanoylamino)butanoyl]amino]butanoyl]amino]-2-oxopentanoyl]amino]pentanoyl]amino]butanoic acid
  参考文献：
  名称：

  Poststatin, a New Inhibitor of Prolyl Endopeptidase. V. Endopeptidase Inhibitory Activity of Poststatin Analogues.

  摘要：

  合成了30个波杀菌蛋白类似物，并测定了它们对脯氨酰内肽酶、人白细胞弹性蛋白酶和组织蛋白酶B的抑制活性。对内肽酶抑制活性来说，α–酮基非常重要，β–取代–β–氨基–α–氧代丙酸部分的S构型比R构型更为优越。用L–亮氨酸代替波杀菌蛋白中的D–亮氨酸得到的类似物对组织蛋白酶B具有很强的抑制活性。将芳香基团引入到P4位和将脯氨酸引入到P2位使对弹性蛋白酶的抑制活性增强。苄氧羰基–L–高苯丙氨酰–(RS)–3–氨基–2–氧代戊二酰–D–亮氨酰–L–缬氨酸对脯氨酰内肽酶的活性约为天然波杀菌蛋白的6倍。

  DOI：

  10.7164/antibiotics.49.890
• 作为产物：
  描述：

  N-Boc-L-缬氨酸 、 Fmoc-L-缬氨酸 、 Fmoc-D-亮氨酸 、 3,3-Diethoxy-4-ethyl-1-(4-nitrophenyl)sulfonylazetidin-2-one 、 alkaline earth salt of/the/ methylsulfuric acid 生成 poststatin
  参考文献：
  名称：

  Solid and solution phase synthesis of α-keto amides via azetidinone ring-opening: Application to the synthesis of poststatin

  摘要：

  3,3-Diethoxy-N-sulfonyl and carbamoyl azetidin-2-ones undergo efficient ring-opening reaction with various amine nucleophiles. Subsequent acid hydrolysis of the ketal moiety generated alpha-keto amides in excellent overall yields. The naturally occurring serine protease inhibitor poststatin was synthesized using this ring-opening reaction as the key step. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00079-9

文献信息

• US6071710A
  申请人：——

  公开号：US6071710A

  公开（公告）日：2000-06-06
• [EN] ANTIKININ COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSES D'ANTIKININE ET LEURS UTILISATIONS
  申请人：MEDICAL UNIVERSITY OF SOUTH CAROLINA

  公开号：WO1998022495A2

  公开（公告）日：1998-05-28

  (EN) An analog of the peptide consisting of RPPGF is provided. Mimetics of RPPGF and its retropeptide, FGPPR, are also provided. A peptide is provided having an antikinin activity and having the sequence X1-R-P-P-G-F-X2, X1-F-G-P-P-R-X2. Provided are methods of screening for a mimetic or analog of RPPGF or FGPPR, screening for an RPPGF receptor, or screening for an antagonist of RPPGF or FGPPR is provided. Methods of treating conditions that can be treated by an antikinin activity and diseases that are associated with an antikinin activity are also provided.(FR) L'invention concerne un analogue du peptide consistant en RPPGF, ainsi que des mimétiques de RPPGF et de son rétropeptide, FGPPR. L'invention concerne également un peptide possédant une activité antikinine et présentant la séquence X1-R-P-P-G-F-X2, X1-F-G-P-P-R-X2; ainsi que des procédés de criblage d'un mimétique ou d'un analogue de RPPGF ou FGPPR, d'un récepteur de RPPGF, ou d'un antagoniste de RPPGF ou de FGPPR. L'invention concerne enfin des procédés de traitement de troubles pouvant être traités par une activité antikinine et de maladies associées à une activité antikinine.
• Poststatin, a New Inhibitor of Prolyl Endopeptidase. V. Endopeptidase Inhibitory Activity of Poststatin Analogues.
  作者：MAKOTO TSUDA、YASUHIKO MURAOKA、MACHIKO NAGAI、TAKAAKI AOYAGI、TOMIO TAKEUCHI

  DOI：10.7164/antibiotics.49.890

  日期：——

  Thirty analogues of poststatin were synthesized, and their inhibitory activities against prolyl endopeptidase, human leukocyte elastase and cathepsin B were measured. The α-ketone was essential and the S configuration was preferable to the R configuration in the β-substituted-β-amino-α-oxopropionic acid moiety of poststatin analogues for endopeptidase inhibitory activity. The analogue in which the D-leucine residue of poststatin was replaced by L-leucine showed strong inhibitory activity to cathepsin B. Introduction of an aromatic group into the P4 position and proline into the P2 position increased inhibitory activity to elastase. Benzyloxycarbonyl-L-homophenylalanyl-(RS)-3-amino-2-oxovaleryl-D-leucyl-L-valine was about 6 times more active to prolyl endopeptidase than natural poststatin.

  合成了30个波杀菌蛋白类似物，并测定了它们对脯氨酰内肽酶、人白细胞弹性蛋白酶和组织蛋白酶B的抑制活性。对内肽酶抑制活性来说，α–酮基非常重要，β–取代–β–氨基–α–氧代丙酸部分的S构型比R构型更为优越。用L–亮氨酸代替波杀菌蛋白中的D–亮氨酸得到的类似物对组织蛋白酶B具有很强的抑制活性。将芳香基团引入到P4位和将脯氨酸引入到P2位使对弹性蛋白酶的抑制活性增强。苄氧羰基–L–高苯丙氨酰–(RS)–3–氨基–2–氧代戊二酰–D–亮氨酰–L–缬氨酸对脯氨酰内肽酶的活性约为天然波杀菌蛋白的6倍。
• Solid and solution phase synthesis of α-keto amides via azetidinone ring-opening: Application to the synthesis of poststatin
  作者：Seock-Kyu Khim、John M. Nuss

  DOI：10.1016/s0040-4039(99)00079-9

  日期：1999.3

  3,3-Diethoxy-N-sulfonyl and carbamoyl azetidin-2-ones undergo efficient ring-opening reaction with various amine nucleophiles. Subsequent acid hydrolysis of the ketal moiety generated alpha-keto amides in excellent overall yields. The naturally occurring serine protease inhibitor poststatin was synthesized using this ring-opening reaction as the key step. (C) 1999 Elsevier Science Ltd. All rights reserved.