(S)-2-[(S)-3-Methyl-2-(3-phenyl-propionylamino)-butyrylamino]-propionic acid methyl ester | 85541-17-9

• 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: (S)-2-[(S)-3-Methyl-2-(3-phenyl-propionylamino)-butyrylamino]-propionic acid methyl ester
• 英文别名: PhCH2CH2COValAlaOCH3；methyl (2S)-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]propanoate
• CAS: 85541-17-9
• 化学式: C₁₈H₂₆N₂O₄
• 分子量: 334.415
• InChiKey: FNFPVZPUELPCCH-BBRMVZONSA-N

物化性质

• 沸点：
  550.1±40.0 °C(Predicted)
• 密度：
  1.100±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-[(S)-3-Methyl-2-(3-phenyl-propionylamino)-butyrylamino]-propionic acid methyl ester 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.5h， 生成 2-[[(2S,3S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]oxirane-2-carbonyl]-[[(2S)-2-[[(2S)-3-methyl-2-(3-phenylpropanoylamino)butanoyl]amino]propanoyl]amino]amino]acetic acid
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Aza-Peptide Epoxides as Selective and Potent Inhibitors of Caspases-1, -3, -6, and -8

  摘要：

  Aza-peptide epoxides, a novel class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. Aza-peptide epoxides with an aza-Asp residue at PI are excellent irreversible inhibitors of caspases-1, -3, -6, and -8 with second-order inhibition rates up to 1910 000 M-1 s(-1). In general, the order of reactivity of aza-peptide epoxides is S'S > R,R > trans > cis. Interestingly, some of the R,R epoxides while being less potent are actually more selective than the S,S epoxides. Our aza-peptide epoxides designed For caspases are stable, potent, and specific inhibitors, as they show little to no inhibition of other proteases such as the aspartyl proteases porcine pepsin, human cathepsin D, plasmepsin 2 from P. falciparum, HIV-1 protease, and the secreted aspartic proteinase 2 (SAP-2) from Candida albicans; the serine proteases granzyme B and alpha-chymotrypsin; and the cysteine proteases cathepsin B and papain (clan CA), and legumain (clan CD).

  DOI：

  10.1021/jm0305016
• 作为产物：
  描述：

  3-酞酰亚胺基丙酸甲酯 、 N-(3-phenylpropionyl)-L-valine 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 (S)-2-[(S)-3-Methyl-2-(3-phenyl-propionylamino)-butyrylamino]-propionic acid methyl ester
  参考文献：
  名称：

  Davies, John S.; Merritt, Raymond K.; Treadgold, Richard C., Journal of the Chemical Society. Perkin transactions I, 1982, # 12, p. 2939 - 2948

  摘要：

  DOI：

文献信息

• Aza-Peptide Epoxides:  A New Class of Inhibitors Selective for Clan CD Cysteine Proteases
  作者：Juliana L. Asgian、Karen Ellis James、Zhao Zhao Li、Wendy Carter、Alan J. Barrett、Jowita Mikolajczyk、Guy S. Salvesen、James C. Powers

  DOI：10.1021/jm025581c

  日期：2002.11.1

  Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 10(5) M(-1) s(-1), with the most potent epoxides having the S,S stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition

  氮杂肽环氧化物是一类新的不可逆的蛋白酶抑制剂，对氏族CD半胱氨酸蛋白酶具有特异性。抑制剂具有高达10（5）M（-1）s（-1）的二阶速率常数，最有效的环氧化物具有S，S立体化学。氮杂-Asn衍生物是有效的豆蔻蛋白酶抑制剂，而氮杂-Asp环氧化物对胱天蛋白酶具有特异性。抑制剂对其他蛋白酶（如胰凝乳蛋白酶，木瓜蛋白酶或组织蛋白酶B）几乎没有抑制作用。
• Method of identifying interleukin 1.beta. converting enzyme inhibitors
  申请人：——

  公开号：US05622830A1

  公开（公告）日：1997-04-22

  A compound of the formula R.sup.1 --A.sup.2 --A.sup.1 --Asp-p-nitroanilide I wherein: A.sup.1 is a residue of any of the naturally occurring .alpha.-amino acids or a homolog, analog or derivative of a natural .alpha.-amino acid; A.sup.2 is a residue of a lipophilic .alpha.-amino acid; R.sup.1 is alkylcarbonyl, phenalkylcarbonyl, alkoxycarbonyl, phenalkoxycarbonyl, alkylaminocarbonyl, phenalkylaminocarbcnyl or R.sup.2 --A.sup.3 wherein A.sup.3 is a residue of a lipophilic .alpha.-amino acid; and R.sup.2 is alkylcarbonyl, alkoxycarbonyl or phenylalkoxycarbonyl, and a method of detecting inhibitors of interleukin 1.beta. converting enzyme (ICE) comprising evaluating a test compound's capacity to inhibit the ICE-induced hydrolysis of a compound of the formula I. The greater the ability of a test compound to inhibit such hydrolysis, the greater its expected activity in treating inflammation as well as diseases whose pathogenesis is induced or sustained by interleukin-1.beta.. Also disclosed is the following intermediate, useful for synthesizing the compounds of formula I: ##STR1##

  该化合物的结构式为R.sup.1 --A.sup.2 --A.sup.1 --Asp-p-nitroanilide I，其中：A.sup.1是任何自然发生的α-氨基酸的残基或自然α-氨基酸的同源物、类似物或衍生物；A.sup.2是脂肪亲和性α-氨基酸的残基；R.sup.1是烷基羰基、苯基烷基羰基、烷氧羰基、苯基烷氧羰基、烷基氨基羰基、苯基烷基氨基羰基或R.sup.2--A.sup.3，其中A.sup.3是脂肪亲和性α-氨基酸的残基；R.sup.2是烷基羰基、烷氧羰基或苯基烷氧羰基。还公开了以下中间体，用于合成式I的化合物：##STR1## 一种检测白细胞介素1β转化酶（ICE）抑制剂的方法，包括评估测试化合物抑制式I化合物的ICE诱导水解能力。测试化合物抑制这种水解的能力越强，其在治疗炎症以及由白细胞介素1β引起或维持病理发生的疾病中的预期活性就越大。
• Paranitroaniline peptides
  申请人：Pfizer Inc.

  公开号：US05498695A1

  公开（公告）日：1996-03-12

  A compound of the formula R.sup.1 -A.sup.2 -A.sup.1 -Asp-p-nitroanilide wherein: A.sup.1 is a residue of any of the naturally occurring .alpha.-amino acids or a homolog, analog or derivative of a natural .alpha.-amino acid; A.sup.2 is a residue of a lipophilic .alpha.-amino acid; R.sup.1 is alkylcarbonyl, phenalkylcarbonyl, alkoxycarbonyl, phenalkoxycarbonyl, alkylaminocarbonyl, phenalkylaminocarbonyl or R.sup.2 -A.sup.3 wherein A.sup.3 is a residue of a lipophilic .alpha.-amino acid; and R.sup.2 is alkylcarbonyl, alkoxycarbonyl or phenylalkoxycarbonyl, and a method of detecting inhibitors of interleukin 1.beta. converting enzyme (ICE) comprising evaluating a test compound's capacity to inhibit the ICE-induced hydrolysis of a compound of the formula I. The greater the ability of a test compound to inhibit such hydrolysis, the greater its expected activity in treating inflammation as well as diseases whose pathogenesis is induced or sustained by interleukin-1.beta.. Also disclosed is the following intermediate, useful for synthesizing the compounds of formula I: ##STR1##

  化合物的公式为R.sup.1-A.sup.2-A.sup.1-Asp-p-nitroanilide，其中：A.sup.1是任何天然α-氨基酸的残基或其同源物、类似物或衍生物；A.sup.2是亲脂性α-氨基酸的残基；R.sup.1是烷基羰基、苯基烷基羰基、烷氧羰基、苯基烷氧羰基、烷基氨基羰基、苯基烷基氨基羰基或R.sup.2-A.sup.3，其中A.sup.3是亲脂性α-氨基酸的残基；而R.sup.2是烷基羰基、烷氧羰基或苯基烷氧羰基。本发明还涉及一种检测白细胞介素1β转化酶（ICE）抑制剂的方法，包括评估测试化合物抑制式I化合物水解的能力。测试化合物抑制这种水解的能力越强，其在治疗炎症以及由白细胞介素1β诱导或维持病理发生的疾病中的活性就越大。还公开了以下中间体，可用于合成式I的化合物： ## STR1 ##