(S)-N,N-diphenyl-2-pyrrolidinecarboxamide | 132139-15-2

• 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)-N,N-diphenyl-2-pyrrolidinecarboxamide
• 英文别名: (S)-N,N-diphenylpyrrolidine-2-carboxamide；(2S)-N,N-diphenylpyrrolidine-2-carboxamide
• CAS: 132139-15-2
• 化学式: C₁₇H₁₈N₂O
• 分子量: 266.343
• InChiKey: IGSHHUKDHVVYLP-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-N,N-diphenyl-2-pyrrolidinecarboxamide 在 N-甲基吗啉 、 N-甲基吡咯烷酮 、 4-二甲氨基吡啶 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 [4-[(E)-4-[[(2S)-1-[(2S)-2-(diphenylcarbamoyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-4-oxobut-2-en-2-yl]phenyl] dihydrogen phosphate
  参考文献：
  名称：

  Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylation and Transcriptional Activity

  摘要：

  Signal transducer and activator of transcription 6 (STAT6) transmits signals from cytokines IL-4 and IL-13 and is activated in allergic airway disease. We are developing phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyrosine residues on IL-4 or IL-13 receptors and subsequent Tyr641 phosphorylation to inhibit the expression of genes contributing to asthma. Structure-affinity relationship studies showed that phosphopeptides based on Tyr631 from IL-4R alpha bind with weak affinity to STAT6, whereas replacing the pY+3 residue with simple aryl and alkyl amides resulted in affinities in the mid to low nM range. A set of phosphatase-stable, cell-permeable prodrug analogues inhibited cytokine-stimulated STAT6 phosphorylation in both Beas-2B human airway cells and primary mouse T-lymphocytes at concentrations as low as 100 nM. IL-13-stimulated expression of CCL26 (eotaxin-3) was inhibited in a dose-dependent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcriptional activity of STAT6.

  DOI：

  10.1021/acs.jmedchem.5b01321
• 作为产物：
  描述：

  (S)-1-(trifluoroacetyl)pyrrolidine-2-carboxylic acid 在 sodium tetrahydroborate 、 氯化亚砜 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 (S)-N,N-diphenyl-2-pyrrolidinecarboxamide
  参考文献：
  名称：

  Enantioselective Synthesis of Binaphthol Derivatives by Oxidative Coupling of Naphthol Derivatives Catalyzed by Chiral Diamine·Copper Complexes

  摘要：

  A highly efficient process of aerobic oxidative coupling of 2-naphthol derivatives catalyzed by 1 mol % of Cu(OH)Cl.TMEDA has been developed, Enantioselective oxidative coupling of naphthols was achieved by the use of 10 mol % of chiral catalysts prepared from proline-derived diamines and cuprous chloride, affording the corresponding binaphthols in good enantioselectivities of up to 78% ee. The ester moiety at the 3-position of the substrate was found to be essential for the good asymmetric induction observed in the present coupling reaction.

  DOI：

  10.1021/jo981808t

文献信息

• [EN] CYCLIZED ACETAMIDO DERIVATIVES AS DNA POLYMERASE THETA INHIBITORS<br/>[FR] DÉRIVÉS ACÉTAMIDO CYCLISÉS UTILISÉS EN TANT QU'INHIBITEURS DE L'ADN POLYMÉRASE THÊTA
  申请人：IDEAYA BIOSCIENCES INC

  公开号：WO2022026565A9

  公开（公告）日：2022-12-08
• Enantioselective Synthesis of Binaphthol Derivatives by Oxidative Coupling of Naphthol Derivatives Catalyzed by Chiral Diamine·Copper Complexes
  作者：Makoto Nakajima、Irie Miyoshi、Kumiko Kanayama、Shun-ichi Hashimoto、Masahiro Noji、Kenji Koga

  DOI：10.1021/jo981808t

  日期：1999.4.1

  A highly efficient process of aerobic oxidative coupling of 2-naphthol derivatives catalyzed by 1 mol % of Cu(OH)Cl.TMEDA has been developed, Enantioselective oxidative coupling of naphthols was achieved by the use of 10 mol % of chiral catalysts prepared from proline-derived diamines and cuprous chloride, affording the corresponding binaphthols in good enantioselectivities of up to 78% ee. The ester moiety at the 3-position of the substrate was found to be essential for the good asymmetric induction observed in the present coupling reaction.
• Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylation and Transcriptional Activity
  作者：Pijus K. Mandal、Pietro Morlacchi、J. Morgan Knight、Todd M. Link、Gilbert R. Lee、Roza Nurieva、Divyendu Singh、Ankur Dhanik、Lydia Kavraki、David B. Corry、John E. Ladbury、John S. McMurray

  DOI：10.1021/acs.jmedchem.5b01321

  日期：2015.11.25

  Signal transducer and activator of transcription 6 (STAT6) transmits signals from cytokines IL-4 and IL-13 and is activated in allergic airway disease. We are developing phosphopeptide mimetics targeting the SH2 domain of STAT6 to block recruitment to phosphotyrosine residues on IL-4 or IL-13 receptors and subsequent Tyr641 phosphorylation to inhibit the expression of genes contributing to asthma. Structure-affinity relationship studies showed that phosphopeptides based on Tyr631 from IL-4R alpha bind with weak affinity to STAT6, whereas replacing the pY+3 residue with simple aryl and alkyl amides resulted in affinities in the mid to low nM range. A set of phosphatase-stable, cell-permeable prodrug analogues inhibited cytokine-stimulated STAT6 phosphorylation in both Beas-2B human airway cells and primary mouse T-lymphocytes at concentrations as low as 100 nM. IL-13-stimulated expression of CCL26 (eotaxin-3) was inhibited in a dose-dependent manner, demonstrating that targeting the SH2 domain blocks both phosphorylation and transcriptional activity of STAT6.