7-glycyl-L-prolylamino-4-methylcoumarin | 67341-40-6

• 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: 7-glycyl-L-prolylamino-4-methylcoumarin
• 英文别名: Gly-Pro-AMC；H-Gly-Pro-AMC；gly-pro-aminomethylcoumarin；Gly-Pro-MCA；L-Prolinamide, glycyl-N-(4-methyl-2-oxo-2H-1-benzopyran-7-yl)-；(2S)-1-(2-aminoacetyl)-N-(4-methyl-2-oxochromen-7-yl)pyrrolidine-2-carboxamide
• CAS: 67341-40-6
• 化学式: C₁₇H₁₉N₃O₄
• 分子量: 329.356
• InChiKey: UTDVHCQTKWTQEA-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-glycyl-L-prolylamino-4-methylcoumarin 在 乙二胺四乙酸 、 dipeptydyl-peptidase DPP₄ 、 sodium chloride 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.5h， 生成 甘油-L-脯氨酸
  参考文献：
  名称：

  Identification and Characterization of Prokaryotic Dipeptidyl-peptidase 5 from Porphyromonas gingivalis

  摘要：

  Background: Dipeptidyl-peptidases (DPPs) are key factors for amino acid metabolism and bacterial growth of asaccharolytic Porphyromonas gingivalis. Results: DPP5, which is specific for Ala and hydrophobic residues, is expressed in the periplasmic space of P. gingivalis.Conclusion: DPP5 was discovered in prokaryotes for the first time. Significance: The discovery of DPP5 expands understanding of amino acid and energy metabolism in prokaryotes. Porphyromonas gingivalis, a Gram-negative asaccharolytic anaerobe, is a major causative organism of chronic periodontitis. Because the bacterium utilizes amino acids as energy and carbon sources and incorporates them mainly as dipeptides, a wide variety of dipeptide production processes mediated by dipeptidyl-peptidases (DPPs) should be beneficial for the organism. In the present study, we identified the fourth P. gingivalis enzyme, DPP5. In a dpp4-7-11-disrupted P. gingivalis ATCC 33277, a DPP7-like activity still remained. PGN_0756 possessed an activity indistinguishable from that of the mutant, and was identified as a bacterial orthologue of fungal DPP5, because of its substrate specificity and 28.5% amino acid sequence identity with an Aspergillus fumigatus entity. P. gingivalis DPP5 was composed of 684 amino acids with a molecular mass of 77,453, and existed as a dimer while migrating at 66 kDa on SDS-PAGE. It preferred Ala and hydrophobic residues, had no activity toward Pro at the P1 position, and no preference for hydrophobic P2 residues, showed an optimal pH of 6.7 in the presence of NaCl, demonstrated K-m and k(cat)/K-m values for Lys-Ala-MCA of 688 m and 11.02 m(-1) s(-1), respectively, and was localized in the periplasm. DPP5 elaborately complemented DPP7 in liberation of dipeptides with hydrophobic P1 residues. Examinations of DPP- and gingipain gene-disrupted mutants indicated that DPP4, DPP5, DPP7, and DPP11 together with Arg- and Lys-gingipains cooperatively liberate most dipeptides from nutrient oligopeptides. This is the first study to report that DPP5 is expressed not only in eukaryotes, but also widely distributed in bacteria and archaea.

  DOI：

  10.1074/jbc.m113.527333
• 作为产物：
  描述：

  甘油-L-脯氨酸 在 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 7-glycyl-L-prolylamino-4-methylcoumarin
  参考文献：
  名称：

  二肽基肽酶4的时间分辨荧光探针及其在抑制剂筛选中的应用

  摘要：

  在世界范围内，2型糖尿病的患病率急剧上升。最近，二肽基肽酶4（DPP4）被确定为潜在的抗糖尿病靶标。已经开发和销售了许多DPP4抑制剂，如西他列汀和维格列汀，但仍需要高级治疗剂。因此，我们开发了筛选DPP4抑制剂的新方法。基于吸收的测量，用对香豆素衍生物7-氨基-4-甲基香豆素的基于硝基苯胺或荧光的测量通常用于筛选蛋白酶抑制剂，包括DPP4抑制剂，但由于干扰了背景吸收和荧光，这些策略不够灵敏，因此产生了许多假阳性和假阴性结果。因此，我们设计并合成了一种新型DPP4探针（Gly-Pro-BCD-Tb; Gly =甘氨酸，Pro =脯氨酸，BCD定义了包含苯胺衍生物作为开/关开关，7-氨基- 4-甲基-2-（1 H）-喹啉酮（cs-124）作为天线部分，以及二亚乙基三胺N，N，N'，N''，N''戊乙酸（DTPA）作为螯合剂部分（Tb = ter）用于时间分辨荧光（TRF）测量。相对于传统的D

  DOI：

  10.1002/chem.201001077

文献信息

• [EN] SITE-SPECIFIC RADIOFLUORINATION OF PEPTIDES WITH 8-[18F]-FLUOROOCTANOIC ACID CATALYZED BY LIPOIC ACID LIGASE<br/>[FR] RADIOFLUORATION SPÉCIFIQUE DE SITE DE PEPTIDES AVEC DE L'ACIDE 8-[18F]FLUOROOCTANOÏQUE CATALYSÉE PAR UNE ACIDE LIPOÏQUE LIGASE
  申请人：UNIV CALIFORNIA

  公开号：WO2017095806A1

  公开（公告）日：2017-06-08

  New methodologies for site-specifically radiolabeling proteins with the PET isotope [18F] are required to generate high quality radiotracers for imaging in both the preclinical and clinical settings. The enzymatic radiofluorination overcomes many of the limitations encountered to date with purely chemical approaches. The bacterial enzyme lipoic acid ligase was used to conjugate [18F]-fluorooctanoic acid to both a small peptide and a Fab antibody fragment. Labeling was site-specific and highly efficient under mild aqueous conditions using small amounts of peptide/protein (1-10 nmol). The labeled construct retained full epitope binding affinity and was stable in mouse serum. Using an optimized reaction scheme, mCi quantities of [18F]-Fab were generated, an amount sufficient for human imaging.

  用PET同位素[18F]对蛋白质进行特异性标记的新方法对于在临床前和临床环境中生成高质量放射示踪剂是必需的。酶促放氟反应克服了迄今为止纯化学方法所遇到的许多限制。细菌酶硫辛酸连接酶被用于将[18F]-氟辛酸与小肽和Fab抗体片段结合。在温和水性条件下，使用少量的肽/蛋白质（1-10 nmol），标记是特异性的且高效的。标记的构建物保留了完整的抗原结合亲和力，并在小鼠血清中稳定。使用优化的反应方案，产生了足够进行人体成像的mCi数量的[18F]-Fab。
• [EN] NA-ACYL DERIVATIVES OF AMINOACYL-2-CYANOPYRROLIDINE-INHIBITORS OF PROLYL ENDOPEPTIDASE AND DIPEPTIDYL PEPTIDASE-IV, HAVING HYPOGLYCEMIC, ANTIHYPOXIC, NEUROPROTECTIVE ACTION AND ACTION OF COGNITIVE FUNCTION IMPROVEMENT<br/>[FR] DÉRIVÉS NA-ACYLE D'AMINOACYL-2-CYANOPYRROLIDINE INHIBANT LA PROLYL ENDOPEPTIDASE ET LA DIPEPTIDYL PEPTIDASE-IV, PRÉSENTANT UNE ACTION HYPOGLYCÉMIQUE, ANTIHYPOXIQUE ET NEUROPROTECTRICE ET AMÉLIORANT LES FONCTIONS COGNITIVES
  申请人：DAPHOT ENTERPRAISES LTD

  公开号：WO2014054980A1

  公开（公告）日：2014-04-10

  The subject of the present invention is nα-acyl derivatives of aminoacyl-2-cyanopyrrolidine - inhibitors of prolyl endopeptidase and dipeptidyl peptidase-iv, having hypoglycemic, antihypoxic, neuroprotective action and action of cognitive function improvement.

  本发明的主题是氨酰基-2-氰基吡咯烷的nα-酰基衍生物 - 脯氨酸内切肽酶和二肽基肽酶-IV的抑制剂，具有降糖、抗缺氧、神经保护作用和改善认知功能的作用。
• [EN] NOVEL COMPOUNDS AS DIPEPTIDYL PEPTIDASE IV (DPP IV) INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS EN TANT QU'INHIBITEURS DE DIPEPTIDYLE PEPTIDASE-IV (DPP-IV)
  申请人：LUPIN LTD

  公开号：WO2009037719A1

  公开（公告）日：2009-03-26

  The present invention is related to novel compounds of the general formula (A), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods of making of the above compounds, and their use as Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors, which are useful in the treatment or prevention of diseases particularly Type II diabetes, other complications related to diabetes and other pathogenic conditions in which DPP IV enzyme is involved.

  本发明涉及一般式（A）的新化合物，它们的互变异构体形式，立体异构体，药学上可接受的盐，含有它们的药物组合物，上述化合物的制备方法，以及它们作为二肽基肽酶-IV（DPP-IV）抑制剂的用途，这些抑制剂在治疗或预防疾病方面特别有用，如II型糖尿病，与糖尿病相关的其他并发症以及DPP IV酶参与的其他病理条件。
• Fibroblast activation protein inhibitor compounds and methods
  申请人：Cohen Frederick

  公开号：US20060276435A1

  公开（公告）日：2006-12-07

  Amino terminus-blocked peptide boronate compounds of Formulas I and II are useful for inhibiting Fibroblast Activation Protein (FAP) and other proteases, and for treating disorders mediated by FAP. Methods of using the amino terminus blocked peptide boronate compounds, and stereoisomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

  公式 I 和 II 的氨基末端阻断肽硼酸化合物可用于抑制成纤维细胞活化蛋白（FAP）和其他蛋白酶，并用于治疗由FAP介导的疾病。公开了使用氨基末端阻断肽硼酸化合物以及其立体异构体、互变异构体、溶剂合物和药用可接受的盐来进行体外、原位和体内对哺乳动物细胞中的这些疾病进行诊断、预防或治疗的方法，或相关的病理状况。
• XANTHINE DERIVATIVE
  申请人：Chengdu Easton Pharmaceutical Co., Ltd.

  公开号：US20150183788A1

  公开（公告）日：2015-07-02

  The present invention discloses a xanthine derivative having the structure of the following general formula (I) or a pharmaceutically acceptable salt thereof; further discloses a preparation method for the xanthine derivative or a pharmaceutically acceptable salt thereof; and further discloses the use of the xanthine derivative or a pharmaceutically acceptable salt thereof. Through experiments of DPP-IV activity inhibition experiments in vitro, impact on glucose tolerance in normal mice and impact on blood glucose in spontaneous diabetic mice, it proves that the compounds and pharmaceutically acceptable salts thereof show good DPP-IV inhibition activity, can be applied to prepare medicines for treating dipeptidyl peptidase IV-related diseases, and more particularly, can be applied to the use of medicines for treating type II diabetes or diseases of abnormal glucose tolerance.

  本发明公开了具有以下一般式（I）的黄嘌呤衍生物或其药学上可接受的盐；进一步公开了该黄嘌呤衍生物或其药学上可接受的盐的制备方法；并进一步公开了该黄嘌呤衍生物或其药学上可接受的盐的用途。通过体外DPP-IV活性抑制实验、对正常小鼠葡萄糖耐量的影响以及对自发性糖尿病小鼠血糖的影响实验证明，这些化合物及其药学上可接受的盐表现出良好的DPP-IV抑制活性，可用于制备治疗二肽基肽酶IV相关疾病的药物，更具体地说，可用于治疗II型糖尿病或异常葡萄糖耐量疾病的药物的应用。