(S)-1-acetyl-2,5-dihydro-1H-pyrrole-2-carboxylic acid | 65518-05-0

• 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: (S)-1-acetyl-2,5-dihydro-1H-pyrrole-2-carboxylic acid
• 英文别名: 1-Acetyl-3,4-didehydro-L-proline；(2S)-1-acetyl-2,5-dihydropyrrole-2-carboxylic acid
• CAS: 65518-05-0
• 化学式: C₇H₉NO₃
• 分子量: 155.153
• InChiKey: VBHKUSGNBBQVID-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-1-acetyl-2,5-dihydro-1H-pyrrole-2-carboxylic acid 在 戴斯-马丁氧化剂 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 (2S)-1-acetyl-N-[(1R)-4-[(aminoiminomethyl)amino]-1-(2-benzothiazolylcarbonyl)butyl]-2,5-dihydro-1H-pyrrole-2-carboxamide trifluoroacetate
  参考文献：
  名称：

  Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-Based Transition-State Analogue Containing a Benzothiazole Ketone

  摘要：

  Inhibitors of human mast cell tryptase (EC 3.4.21.59) have therapeutic potential for treating allergic or inflammatory disorders. We have investigated transition-state mimetics possessing a heterocycle-activated ketone group and identified in particular benzothiazole ketone (2S)-6 (RWJ-56423) as a potent, reversible, low-molecular-weight tryptase inhibitor with a K-i value of 10 nM. A single-crystal X-ray analysis of the sulfate salt of (2S)-6 confirmed the stereochemistry. Analogues 12 and 15-17 are also potent tryptase inhibitors. Although RWJ-56423 potently inhibits trypsin (K-i = 8.1 nM), it is selective vs other serine proteases, such as kallikrein, plasmin, and thrombin. We obtained an X-ray structure of (2S)-6 complexed with bovine trypsin (1.9-Angstrom resolution), which depicts inter alia a hemiketal involving Ser-189, and hydrogen bonds with His-57 and Gln-192. Aerosol administration of 6 (2R,2S; RWJ-58643) to allergic sheep effectively antagonized antigen-induced asthmatic responses, with 70-75% blockade of the early response and complete ablation of the late response and airway hyperresponsiveness.

  DOI：

  10.1021/jm030050p
• 作为产物：
  描述：

  methyl (S)-1-acetyl-2,5-dihydro-1H-pyrrole-2-carboxylate 在 水 、 sodium hydroxide 作用下， 反应 1.5h， 生成 (S)-1-acetyl-2,5-dihydro-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  3,4-脱氢脯氨酸残基（未折叠的脯氨酸）的顺式-反式-酰胺异构体。

  摘要：

  脯氨酸（Pro）在各种生物化学和物理化学观点中都是出色的氨基酸，尤其是考虑到肽基-Pro酰胺键的顺反异构体时。可以使用各种Pro类似物阐明Pro在化学或生物系统中的作用及其功能工程。在这里，我们报告了一项实验工作，研究了两个具有3,4-双键的Pro类似物的基本理化性质：3,4-脱氢脯氨酸和4-三氟甲基-3,4-脱氢脯氨酸。与先前的理论计算相一致，二者在其晶体结构中均指示出平坦的吡咯啉环。在溶液中，与Pro和4-三氟甲基脯氨酸衍生物相比，该肽模拟物表现出几乎不变的反式/顺式比例平衡。最后，我们证明3

  DOI：

  10.3762/bjoc.12.57

文献信息

• Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-Based Transition-State Analogue Containing a Benzothiazole Ketone
  作者：Michael J. Costanzo、Stephen C. Yabut、Harold R. Almond,、Patricia Andrade-Gordon、Thomas W. Corcoran、Lawrence de Garavilla、Jack A. Kauffman、William M. Abraham、Rosario Recacha、Debashish Chattopadhyay、Bruce E. Maryanoff

  DOI：10.1021/jm030050p

  日期：2003.8.1

  Inhibitors of human mast cell tryptase (EC 3.4.21.59) have therapeutic potential for treating allergic or inflammatory disorders. We have investigated transition-state mimetics possessing a heterocycle-activated ketone group and identified in particular benzothiazole ketone (2S)-6 (RWJ-56423) as a potent, reversible, low-molecular-weight tryptase inhibitor with a K-i value of 10 nM. A single-crystal X-ray analysis of the sulfate salt of (2S)-6 confirmed the stereochemistry. Analogues 12 and 15-17 are also potent tryptase inhibitors. Although RWJ-56423 potently inhibits trypsin (K-i = 8.1 nM), it is selective vs other serine proteases, such as kallikrein, plasmin, and thrombin. We obtained an X-ray structure of (2S)-6 complexed with bovine trypsin (1.9-Angstrom resolution), which depicts inter alia a hemiketal involving Ser-189, and hydrogen bonds with His-57 and Gln-192. Aerosol administration of 6 (2R,2S; RWJ-58643) to allergic sheep effectively antagonized antigen-induced asthmatic responses, with 70-75% blockade of the early response and complete ablation of the late response and airway hyperresponsiveness.
• <i>cis</i>–<i>trans</i>-Amide isomerism of the 3,4-dehydroproline residue, the ‘unpuckered’ proline
  作者：Vladimir Kubyshkin、Nediljko Budisa

  DOI：10.3762/bjoc.12.57

  日期：——

  theoretical calculations. In solution, the peptide mimics exhibit an almost unchanged equilibrium of the trans/cis ratios compared to that of Pro and 4-trifluoromethylproline derivatives. Finally we demonstrate that the 3,4-double bond in the investigated structures leads to an increase of the amide rotational barriers, presumably due to an interplay with the transition state.

  脯氨酸（Pro）在各种生物化学和物理化学观点中都是出色的氨基酸，尤其是考虑到肽基-Pro酰胺键的顺反异构体时。可以使用各种Pro类似物阐明Pro在化学或生物系统中的作用及其功能工程。在这里，我们报告了一项实验工作，研究了两个具有3,4-双键的Pro类似物的基本理化性质：3,4-脱氢脯氨酸和4-三氟甲基-3,4-脱氢脯氨酸。与先前的理论计算相一致，二者在其晶体结构中均指示出平坦的吡咯啉环。在溶液中，与Pro和4-三氟甲基脯氨酸衍生物相比，该肽模拟物表现出几乎不变的反式/顺式比例平衡。最后，我们证明3