(R)-1-(3-nitrophenylsulfonyl)pyrrolidine-2-carboxylic acid | 910481-85-5

• 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: (R)-1-(3-nitrophenylsulfonyl)pyrrolidine-2-carboxylic acid
• 英文别名: (2R)-1-(3-nitrophenyl)sulfonylpyrrolidine-2-carboxylic acid
• CAS: 910481-85-5
• 化学式: C₁₁H₁₂N₂O₆S
• 分子量: 300.292
• InChiKey: XEKBNNVVCDSGBZ-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-1-(3-nitrophenylsulfonyl)pyrrolidine-2-carboxylic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (R)-1-(3-nitrophenylsulfonyl)-N-((R,S)-1-oxo-3-phenylpropan-2-yl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis, Calpain Inhibitory Activity, and Cytotoxicity of P₂-Substituted Proline and Thiaproline Peptidyl Aldehydes and Peptidyl α-Ketoamides

  摘要：

  Calpain is a cytosolic cysteine endopeptidase that has been implicated in a number of disorders including cancer. We have synthesized and studied the mu-calpain inhibitory activity and cytotoxicity of peptidyl aldehydes and peptidyl alpha-ketoamides with N-substituted D-proline or L-thiaproline residues at the P-2-postion. The most potent and most selective members of the series were (R)-1-(4-nitrophenylsulfonyl)-N-((R, S)-1-oxo- 3-phenylpropan-2-yl) pyrrolidine-2-carboxamide (1j) and (R)-1-(4-iodophenylsulfonyl)-N-((R,S)-1-oxo-3- phenylpropan-2-yl) pyrrolidine-2-carboxamide (1n). The compounds inhibited A-calpain with K-i values of 0.02 mu M and 0.03 mu M, respectively, and displayed over 180-fold (1j) and 130-fold ( 1n) greater affinity for mu-calpain compared to cathepsin B. The cytotoxic effect of the compounds was evaluated in two leukemia cell lines (Daudi and Jurkat) and three solid tumor cell lines (DU-145, PC-3, and HeLa). Generally the compounds were modestly cytotoxic and displayed no correlation between the cytotoxic activity and mu-calpain inhibition.

  DOI：

  10.1021/jm050849w
• 作为产物：
  描述：

  3-硝基苯磺酰氯 、 D-脯氨酸 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以81.6%的产率得到(R)-1-(3-nitrophenylsulfonyl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Synthesis, Calpain Inhibitory Activity, and Cytotoxicity of P₂-Substituted Proline and Thiaproline Peptidyl Aldehydes and Peptidyl α-Ketoamides

  摘要：

  Calpain is a cytosolic cysteine endopeptidase that has been implicated in a number of disorders including cancer. We have synthesized and studied the mu-calpain inhibitory activity and cytotoxicity of peptidyl aldehydes and peptidyl alpha-ketoamides with N-substituted D-proline or L-thiaproline residues at the P-2-postion. The most potent and most selective members of the series were (R)-1-(4-nitrophenylsulfonyl)-N-((R, S)-1-oxo- 3-phenylpropan-2-yl) pyrrolidine-2-carboxamide (1j) and (R)-1-(4-iodophenylsulfonyl)-N-((R,S)-1-oxo-3- phenylpropan-2-yl) pyrrolidine-2-carboxamide (1n). The compounds inhibited A-calpain with K-i values of 0.02 mu M and 0.03 mu M, respectively, and displayed over 180-fold (1j) and 130-fold ( 1n) greater affinity for mu-calpain compared to cathepsin B. The cytotoxic effect of the compounds was evaluated in two leukemia cell lines (Daudi and Jurkat) and three solid tumor cell lines (DU-145, PC-3, and HeLa). Generally the compounds were modestly cytotoxic and displayed no correlation between the cytotoxic activity and mu-calpain inhibition.

  DOI：

  10.1021/jm050849w

文献信息

• DISUBSTITUTED 3,4-DIAMINO-3-CYCLOBUTENE-1,2-DIONE COMPOUNDS FOR USE IN THE TREATMENT OF CHEMOKINE-MEDIATED PATHOLOGIES
  申请人：GALDERMA RESEARCH & DEVELOPMENT

  公开号：US20140309208A1

  公开（公告）日：2014-10-16

  Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds are disclosed that are represented by general formula (I). Also disclosed, are pharmaceutical compositions including these compounds and methods of using these compounds and compositions for the treatment of chemokine-mediated pathologies.

  折叠环丙烯-1,2-二酮的二取代3,4-二氨基化合物的一般式(I)已被披露。还披露了包括这些化合物的药物组合物以及使用这些化合物和组合物治疗趋化因子介导的病理的方法。
• COMPOSÉS DI-SUBSTITUÉS DE LA DIAMINO-3,4-CYCLOBUTÈNE-3-DIONE-1,2 UTILES DANS LE TRAITEMENT DE PATHOLOGIES MÉDIÉES PAR DES CHIMIOKINES
  申请人：Galderma Research & Development

  公开号：EP2771334A1

  公开（公告）日：2014-09-03
• US9090596B2
  申请人：——

  公开号：US9090596B2

  公开（公告）日：2015-07-28
• US9526732B2
  申请人：——

  公开号：US9526732B2

  公开（公告）日：2016-12-27
• [EN] DISUBSTITUTED 3,4-DIAMINO-3-CYCLOBUTENE-1,2-DIONE COMPOUNDS FOR USE IN THE TREATMENT OF CHEMOKINE-MEDIATED PATHOLOGIES<br/>[FR] COMPOSÉS DI-SUBSTITUÉS DE LA DIAMINO-3,4-CYCLOBUTÈNE-3-DIONE-1,2 UTILES DANS LE TRAITEMENT DE PATHOLOGIES MÉDIÉES PAR DES CHIMIOKINES
  申请人：GALDERMA RES & DEV

  公开号：WO2013061005A1

  公开（公告）日：2013-05-02

  La présente invention porte sur de nouveaux composés di-substitués de la diamino-3,4- cyclobutène-3-dione-l,2, répondant à la formule générale (I) suivante : sur les compositions pharmaceutiques contenant ces composés ainsi que sur l'utilisation de ces composés et de ces compositions pour le traitement de pathologies médiées par des chimiokines.