((S)-3-Amino-2-oxo-pyrrolidin-1-yl)-acetic acid methyl ester | 758668-34-7

• 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)-3-Amino-2-oxo-pyrrolidin-1-yl)-acetic acid methyl ester
• 英文别名: methyl 2-[(3S)-3-amino-2-oxopyrrolidin-1-yl]acetate
• CAS: 758668-34-7
• 化学式: C₇H₁₂N₂O₃
• 分子量: 172.184
• InChiKey: LOGZBAKJOCUEMJ-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ((S)-3-Amino-2-oxo-pyrrolidin-1-yl)-acetic acid methyl ester 在 lithium hydroxide monohydrate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  Structure-based design and optimization of potent inhibitors of the adenoviral protease

  摘要：

  Adenoviral infections are associated with a wide range of acute diseases, among which ocular viral conjunctivitis (EKC) and disseminated disease in immunocompromised patients. To date, no approved specific anti-adenoviral drug is available, but there is a growing need for an effective treatment of such infections. The adenoviral protease, adenain, plays a crucial role for the viral lifecycle and thus represents an attractive therapeutic target. Structure-guided design with the objective to depeptidize tetrapeptide nitrile 1 led to the novel chemotype 2. Optimization of scaffold 2 resulted in picomolar adenain inhibitors 3a and 3b. In addition, a complementary series of irreversible vinyl sulfone containing inhibitors were rationally designed, prepared and evaluated against adenoviral protease. High resolution X-ray co-crystal structures of representatives of each series proves the successful design of these inhibitors and provides an excellent basis for future medicinal chemistry optimization of these compounds. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.057
• 作为产物：
  描述：

  (S)-(3-n-boc-氨基-2-氧代-吡咯烷-1-基)-乙酸 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 为溶剂， 反应 2.33h， 生成 ((S)-3-Amino-2-oxo-pyrrolidin-1-yl)-acetic acid methyl ester
  参考文献：
  名称：

  通过构象约束的Pro-Leu-Gly-NH2类似物调节多巴胺受体。

  摘要：

  已合成了两个系列的Pro-Leu-Gly-NH2（PLG）构象受限的类似物。在一系列类似物中，PLG的Leu-Gly-NH2二肽片段被γ-内酰胺残基3（S）-和3（R）-氨基-2-氧吡咯烷乙酰胺和δ-内酰胺残基3（S）取代-氨基-2-氧代哌啶乙酰胺。还合成了小于Glu-Leu-Gly-NH 2的相应的γ-内酰胺类似物。在第二系列类似物中，PLG的甘氨酰胺残基被2-酮戊哌嗪，3（S）-氨基-2-吡咯烷酮和3（S）-氨基-2-哌啶酮残基取代。测试上述类似物增强多巴胺受体激动剂2-氨基-6,7-二羟基-1,2,3,4-四氢萘（ADTN）与纹状体多巴胺受体结合的能力。在这项研究中合成的受PLG构象约束的类似物中，只有γ-内酰胺类似物3（R）-（NL-脯氨酰胺基）-2-氧代-1-吡咯烷乙酰胺（3）被发现具有显着活性。在预温育条件下，该类似物的活性是PLG的10,000倍。它在10（-9）和10（-10）M浓度下显着增强了ADTN的结合。

  DOI：

  10.1021/jm00402a031

文献信息

• Valle, Giovanni; Crisma, Marco; Toniolo, Claudio, journal of the chemical society-perkin transactions 2, 1989, p. 83 - 88
  作者：Valle, Giovanni、Crisma, Marco、Toniolo, Claudio、Yu, Kou-Long、Johnson, Rodney L.

  DOI：——

  日期：——
• Dopamine receptor modulation by conformationally constrained analogs of Pro-Leu-Gly-NH2
  作者：Kuo Long Yu、G. Rajakumar、Lalit K. Srivastava、Ram K. Mishra、Rodney L. Johnson

  DOI：10.1021/jm00402a031

  日期：1988.7

  Leu-Gly-NH2 dipeptide segment of PLG was replaced with the gamma-lactam residues 3(S)- and 3(R)-amino-2-oxopyrrolidineacetamide and the delta-lactam residue 3(S)-amino-2-oxopiperidineacetamide. The corresponding gamma-lactam analogues of less than Glu-Leu-Gly-NH2 were also synthesized. In a second series of analogues, the glycinamide residue of PLG was replaced with the 2-ketopiperazine, 3(S)-amino-2-pyrrolidone

  已合成了两个系列的Pro-Leu-Gly-NH2（PLG）构象受限的类似物。在一系列类似物中，PLG的Leu-Gly-NH2二肽片段被γ-内酰胺残基3（S）-和3（R）-氨基-2-氧吡咯烷乙酰胺和δ-内酰胺残基3（S）取代-氨基-2-氧代哌啶乙酰胺。还合成了小于Glu-Leu-Gly-NH 2的相应的γ-内酰胺类似物。在第二系列类似物中，PLG的甘氨酰胺残基被2-酮戊哌嗪，3（S）-氨基-2-吡咯烷酮和3（S）-氨基-2-哌啶酮残基取代。测试上述类似物增强多巴胺受体激动剂2-氨基-6,7-二羟基-1,2,3,4-四氢萘（ADTN）与纹状体多巴胺受体结合的能力。在这项研究中合成的受PLG构象约束的类似物中，只有γ-内酰胺类似物3（R）-（NL-脯氨酰胺基）-2-氧代-1-吡咯烷乙酰胺（3）被发现具有显着活性。在预温育条件下，该类似物的活性是PLG的10,000倍。它在10（-9）和10（-10）M浓度下显着增强了ADTN的结合。
• Structure-based design and optimization of potent inhibitors of the adenoviral protease
  作者：Philipp Grosche、Finton Sirockin、Aengus Mac Sweeney、Paul Ramage、Paul Erbel、Samu Melkko、Anna Bernardi、Nicola Hughes、David Ellis、Keith D. Combrink、Nadine Jarousse、Eva Altmann

  DOI：10.1016/j.bmcl.2014.12.057

  日期：2015.2

  Adenoviral infections are associated with a wide range of acute diseases, among which ocular viral conjunctivitis (EKC) and disseminated disease in immunocompromised patients. To date, no approved specific anti-adenoviral drug is available, but there is a growing need for an effective treatment of such infections. The adenoviral protease, adenain, plays a crucial role for the viral lifecycle and thus represents an attractive therapeutic target. Structure-guided design with the objective to depeptidize tetrapeptide nitrile 1 led to the novel chemotype 2. Optimization of scaffold 2 resulted in picomolar adenain inhibitors 3a and 3b. In addition, a complementary series of irreversible vinyl sulfone containing inhibitors were rationally designed, prepared and evaluated against adenoviral protease. High resolution X-ray co-crystal structures of representatives of each series proves the successful design of these inhibitors and provides an excellent basis for future medicinal chemistry optimization of these compounds. (C) 2014 Elsevier Ltd. All rights reserved.