(S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate | 1428264-81-6

• 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-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate
• 英文别名: (S)-2-(2-cyanopyrrolidin-1-yl)-2-oxoethanaminium 4-methylbenzenesulfonate；[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]azanium;4-methylbenzenesulfonate
• CAS: 1428264-81-6
• 化学式: C₇H₈O₃S*C₇H₁₁N₃O
• 分子量: 325.389
• InChiKey: OIVIWXUSSXMJBX-RGMNGODLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate 在 偶氮二甲酸二异丙酯 、 1-羟基苯并三唑 、 三苯基膦 、 三氟乙酸 、 O‐(1H‐benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.08h， 生成 2-[4-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]carbamoyl]quinolin-7-yl]oxyacetic acid
  参考文献：
  名称：

  [EN] FIBROBLAST ACTIVATION PROTEIN-TARGETED COMPOSITIONS AND METHODS OF USE THEREOF
  [FR] COMPOSITIONS CIBLANT DES PROTÉINES D'ACTIVATION DES FIBROBLASTES ET LEURS MÉTHODES D'UTILISATION

  摘要：

  Disclosed are compounds, compositions, and methods useful for imaging and treating tumor cells in a subject. In particular, the compounds have the structure of Formula I is useful in the dislocsed imaging methods : (I). The variables in Formula (I) are defined herein.

  公开号：

  WO2024026072A1
• 作为产物：
  描述：

  L-脯氨酰胺 在 吡啶 、 N,N-二异丙基乙胺 、 三氟乙酸酐 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 28.5h， 生成 (S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate
  参考文献：
  名称：

  Selective Inhibitors of Fibroblast Activation Protein (FAP) with a (4-Quinolinoyl)-glycyl-2-cyanopyrrolidine Scaffold

  摘要：

  Fibroblast activation protein (FAP) is a serine protease that is generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) and prolyl oligopeptidase (PREP). We present the discovery of a new class of FAP inhibitors with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. We have explored the effects of substituting the quinoline ring and varying the position of its sp(2) hybridized nitrogen atom. The most promising inhibitors combined low nanomolar FAP inhibition and high selectivity indices (>10(3)) with respect to both the DPPs and PREP. Preliminary experiments on a representative inhibitor demonstrate that plasma stability, kinetic solubility, and log D of this class of compounds can be expected to be satisfactory.

  DOI：

  10.1021/ml300410d

文献信息

• Extended Structure–Activity Relationship and Pharmacokinetic Investigation of (4-Quinolinoyl)glycyl-2-cyanopyrrolidine Inhibitors of Fibroblast Activation Protein (FAP)
  作者：Koen Jansen、Leen Heirbaut、Robert Verkerk、Jonathan D. Cheng、Jurgen Joossens、Paul Cos、Louis Maes、Anne-Marie Lambeir、Ingrid De Meester、Koen Augustyns、Pieter Van der Veken

  DOI：10.1021/jm500031w

  日期：2014.4.10

  (2S)-cyanoPro scaffold as a possible entry to highly potent and selective FAP inhibitors. In the present study, we explore in detail the structure–activity relationship around this core scaffold. We report extensively optimized compounds that display low nanomolar inhibitory potency and high selectivity against the related dipeptidyl peptidases (DPPs) DPPIV, DPP9, DPPII, and prolyl oligopeptidase (PREP)

  成纤维细胞活化蛋白（FAP）是一种与二肽基肽酶IV（DPPIV）相关的丝氨酸蛋白酶。它已令人信服地与涉及细胞外基质重塑的多种疾病状态联系在一起。FAP抑制已被研究作为这些疾病中的几种的治疗选择，迄今为止，大多数注意力都集中在肿瘤学应用上。我们之前发现了N -4-喹啉基-Gly-（2 S）-cyanoPro支架可能是高效和选择性FAP抑制剂的一种可能。在本研究中，我们将详细探讨围绕该核心支架的结构与活性之间的关系。我们报告了广泛优化的化合物，这些化合物对相关的二肽基肽酶（DPPs）DPPIV，DPP9，DPPII和脯氨酰寡肽酶（PREP）表现出低纳摩尔抑制力和高选择性。发现所选化合物的log  D值，血浆稳定性和微粒体稳定性非常令人满意。选定抑制剂在小鼠体内的药代动力学评估表明，其口服生物利用度高，血浆半衰期高，并且具有体内选择性和完全抑制FAP的潜力。
• [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。
• FAP INHIBITOR
  申请人：UNIVERSITÄT HEIDELBERG

  公开号：US20210038749A1

  公开（公告）日：2021-02-11

  The present invention relates to a compound of formula (I), a pharmaceutical composition comprising or consisting of said compound, a kit comprising or consisting of said compound or pharmaceutical composition and use of the compound or pharmaceutical composition in the diagnosis or treatment of a disease characterized by overexpression of fibroblast activation protein (FAP).
• US9346814B2
  申请人：——

  公开号：US9346814B2

  公开（公告）日：2016-05-24