(S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-1-naphthamide | 1374770-21-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-1-naphthamide
• 英文别名: N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]naphthalene-1-carboxamide
• CAS: 1374770-21-4
• 化学式: C₁₈H₁₅F₂N₃O₂
• 分子量: 343.333
• InChiKey: YJNMDFARAFJSEZ-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 吡啶 、 三氟乙酸 作用下， 生成 (S)-N-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethyl)-1-naphthamide
  参考文献：
  名称：

  Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity

  摘要：

  A series of N-acylated glycyl-(2-cyano) pyrrolidines were synthesized with the aim of generating structure-activity relationship (SAR) data for this class of compounds as inhibitors of fibroblast activation protein (FAP). Specifically, the influence of (1) the choice of the N-acyl group and (2) structural modification of the 2-cyanopyrrolidine residue were investigated. The inhibitors displayed inhibitory potency in the micromolar to nanomolar range and showed good to excellent selectivity with respect to the proline selective dipeptidyl peptidases (DPPs) DPP IV, DPP9 and DPP II. Additionally, selectivity for FAP with respect to prolyl oligopeptidase (PREP) is reported. Not unexpectedly, the latter data suggest significant overlap in the pharmacophoric features that define FAP or PREP-inhibitory activity and underscore the importance of systematically evaluating the FAP/PREP-selectivity index for inhibitors of either of these two enzymes. Finally, this study forwards several compounds that can serve as leads or prototypic structures for future FAP-selective-inhibitor discovery. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.107

文献信息

• [EN] NOVEL FAP INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE FAP
  申请人：UNIV ANTWERPEN

  公开号：WO2013107820A1

  公开（公告）日：2013-07-25

  The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.

  本发明涉及对FAP（成纤维细胞活化蛋白）具有高选择性和特异性的新型抑制剂。所述抑制剂可用作人类和/或兽药，特别是用于治疗和/或预防FAP相关疾病，如但不限于增殖性疾病。
• NOVEL FAP INHIBITORS
  申请人：UNIVERSITEIT ANTWERPEN

  公开号：US20140357650A1

  公开（公告）日：2014-12-04

  The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.

  本发明涉及具有高选择性和特异性的新型抑制剂，用于FAP（成纤维细胞激活蛋白）。所述抑制剂可用作人类和/或兽医药物，特别用于治疗和/或预防与FAP相关的疾病，如但不限于增殖性疾病。
• US9346814B2
  申请人：——

  公开号：US9346814B2

  公开（公告）日：2016-05-24
• Acylated Gly-(2-cyano)pyrrolidines as inhibitors of fibroblast activation protein (FAP) and the issue of FAP/prolyl oligopeptidase (PREP)-selectivity
  作者：Oxana Ryabtsova、Koen Jansen、Sebastiaan Van Goethem、Jurgen Joossens、Jonathan D. Cheng、Anne-Marie Lambeir、Ingrid De Meester、Koen Augustyns、Pieter Van der Veken

  DOI：10.1016/j.bmcl.2012.03.107

  日期：2012.5

  A series of N-acylated glycyl-(2-cyano) pyrrolidines were synthesized with the aim of generating structure-activity relationship (SAR) data for this class of compounds as inhibitors of fibroblast activation protein (FAP). Specifically, the influence of (1) the choice of the N-acyl group and (2) structural modification of the 2-cyanopyrrolidine residue were investigated. The inhibitors displayed inhibitory potency in the micromolar to nanomolar range and showed good to excellent selectivity with respect to the proline selective dipeptidyl peptidases (DPPs) DPP IV, DPP9 and DPP II. Additionally, selectivity for FAP with respect to prolyl oligopeptidase (PREP) is reported. Not unexpectedly, the latter data suggest significant overlap in the pharmacophoric features that define FAP or PREP-inhibitory activity and underscore the importance of systematically evaluating the FAP/PREP-selectivity index for inhibitors of either of these two enzymes. Finally, this study forwards several compounds that can serve as leads or prototypic structures for future FAP-selective-inhibitor discovery. (C) 2012 Elsevier Ltd. All rights reserved.