1-(1H-benzo[d]imidazol-6-yl)-5-(2,3-difluorophenyl)-3-hydroxy-4-methyl-1H-pyrrol-2(5H)-one | 1024609-09-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 1-(1H-benzo[d]imidazol-6-yl)-5-(2,3-difluorophenyl)-3-hydroxy-4-methyl-1H-pyrrol-2(5H)-one
• 英文别名: 1-(3H-benzimidazol-5-yl)-2-(2,3-difluorophenyl)-4-hydroxy-3-methyl-2H-pyrrol-5-one
• CAS: 1024609-09-3
• 化学式: C₁₈H₁₃F₂N₃O₂
• 分子量: 341.317
• InChiKey: MHAAGLPVTPWYEA-UHFFFAOYSA-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：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  69.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  丙酮酸乙酯 、 2,3-二氟苯甲醛 、 5-氨基苯并咪唑 在 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 23.0h， 以46%的产率得到1-(1H-benzo[d]imidazol-6-yl)-5-(2,3-difluorophenyl)-3-hydroxy-4-methyl-1H-pyrrol-2(5H)-one
  参考文献：
  名称：

  WO2008/55945

  摘要：

  公开号：

文献信息

• RADIOLABELLED GLUTAMINYL CYCLASE (QC) INHIBITORS AND USES OF SAME
  申请人：Heiser Ulrich

  公开号：US20120301398A1

  公开（公告）日：2012-11-29

  Radiolabeled glutaminylcyclase (QC) inhibitors as imaging agents, in particular, but not exclusively, as medical imaging agents for the detection of neurological disorders; and pharmaceutical compositions, methods and kits for detecting neurological disorders, using the radiolabeled inhibitors.

  放射性标记的谷氨酰环化酶（QC）抑制剂作为成像剂，特别是但不限于作为用于检测神经系统疾病的医学成像剂；以及使用这些放射性标记抑制剂检测神经系统疾病的药物组合物、方法和工具包。
• NOVEL INHIBITORS
  申请人：Heiser Ulrich

  公开号：US20110224254A1

  公开（公告）日：2011-09-15

  Novel heterocyclic derivatives as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

  新型杂环衍生物作为谷氨酰环化酶（QC，EC 2.3.2.5）的抑制剂。QC催化N-末端谷氨酸残基的分子内环化，生成丙酸内酰胺（5-氧代脯氨酰，pGlu*），同时释放氨，并催化N-末端谷氨酸残基的分子内环化，生成丙酸内酰胺，并释放水。
• Novel Inhibitors of Glutaminyl Cyclase
  申请人：Thormann Michael

  公开号：US20090269301A1

  公开（公告）日：2009-10-29

  The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, R 1 represents heteroaryl, -carbocyclyl-heteroaryl, -alkenylheteroaryl or -alkylheteroaryl; R 2 represents hydrogen; halogen; alkenyl; alkynyl; -alkenylaryl; -alkenylheteroaryl; alkyl, which may optionally be substituted by one or more groups selected from halogen, hydroxyl, alkoxy-, -thioalkyl, —C(O)OH and —C(O)O-alkyl; carbocyclyl, which may optionally be substituted by one or more groups selected from alkyl, halogen, hydroxyl, alkoxy-, -thioalkyl, —C(O)OH and —C(O)O-alkyl; -alkylcarbocyclyl; -alkylheterocyclyl; aryl; heteroaryl; heterocyclyl; -alkylaryl; -alkyl(aryl) 2 , -alkylheteroaryl; -aryl-heteroaryl; -heterocyclyl-aryl; -aryl-aryl; -heteroaryl-aryl; -heteroaryl-heteroaryl, and —C(O)R 4 ; R 3 represents halogen; alkyl optionally substituted by one or more groups selected from halogen, hydroxyl, alkoxy, thioalkyl, —C(O)OH and —C(O)O-alkyl; aryl; heteroaryl; —C(O)R 5 ; R 4 and R 5 independently represent alkyl, aryl, heteroaryl, -alkylaryl, -alkylheteroaryl, carbocyclyl, heterocyclyl, -alkylcarbocyclyl and -alkylheterocyclyl, with the proviso that, when R 1 is imidazolyl, -carbocyclyl-imidazolyl, -alkenyl-imidazolyl or -alkyl-imidazolyl, then R 3 may not be —C(O)R 5 .

  本发明涉及式（I）化合物，其组合物和用于疾病治疗的用途。其中，R1代表杂环芳基，-碳环芳基-杂环芳基，-烯基杂环芳基或-烷基杂环芳基；R2代表氢，卤素，烯基，炔基，-烯基芳基，-烯基杂环芳基，烷基，可以选择被一个或多个从卤素，羟基，烷氧基，硫代烷基，-C（O）OH和-C（O）O-烷基中选择的基团取代的烷基，可以选择被一个或多个从烷基，卤素，羟基，烷氧基，硫代烷基，-C（O）OH和-C（O）O-烷基中选择的基团取代的碳环芳基，可以选择被一个或多个从烷基，卤素，羟基，烷氧基，硫代烷基，-C（O）OH和-C（O）O-烷基中选择的基团取代的-烷基碳环芳基，-烷基杂环芳基，芳基，杂环芳基，杂环芳基，-烷基芳基2，-烷基杂环芳基，-芳基杂环芳基，-杂环芳基-芳基，-芳基-芳基，-杂环芳基-芳基，-杂环芳基-杂环芳基和-C（O）R4；R3代表卤素，烷基，可以选择被一个或多个从卤素，羟基，烷氧基，硫代烷基，-C（O）OH和-C（O）O-烷基中选择的基团取代的烷基，芳基，杂环芳基和-C（O）R5；R4和R5独立地代表烷基，芳基，杂环芳基，-烷基芳基，-烷基杂环芳基，碳环芳基，杂环芳基，-烷基碳环芳基和-烷基杂环芳基，但当R1是咪唑基，-碳环芳基-咪唑基，-烯基咪唑基或-烷基咪唑基时，R3不能是-C（O）R5。
• TREATING PATHOLOGICAL CONDITIONS BY DIRECT AND INDIRECT TARGETING OF SIRPA - CD47 INTERACTION
  申请人：Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis

  公开号：EP3747438A1

  公开（公告）日：2020-12-09

  The present invention relates to active agents or compounds as well as pharmaceutical compositions comprising said compounds, which are capable of reducing or inhibiting or blocking the enzymatic activity of the glutaminyl-peptide cyclotransferase (QPCT) protein, the glutaminyl-peptide cyclotransferase-like protein (QPCTL) protein, or combinations thereof or are capable of reducing or inhibiting the expression of QPCT gene, the QPCTL gene, or combinations thereof. Also provided are methods for screening or selecting for said compounds. The present invention further relates to a pharmaceutical composition comprising a first active agent for use in a method of treating a condition in a subject that would benefit from reducing the signaling or the binding between SIRPa and CD47 in the subject (e.g. cancer), wherein the method of treating comprises reducing expression or enzymatic activity of QPCTL, QPCT, or combinations thereof in the cell with CD47 on the surface. The compounds and pharmaceutical compositions of the invention may be particularly useful for treating a subject suffering from a disease or condition involving the CD47-SIRPa signaling axis such including e.g., various cancer types, atherosclerosis, fibrotic diseases, and infectious diseases.

  本发明涉及活性剂或化合物以及包含所述化合物的药物组合物，它们能够降低或抑制或阻断谷氨酰胺酰肽环转酶（QPCT）蛋白、谷氨酰胺酰肽环转酶样蛋白（QPCTL）蛋白或其组合的酶活性，或者能够降低或抑制QPCT基因、QPCTL基因或其组合的表达。还提供了筛选或选择所述化合物的方法。本发明进一步涉及一种药物组合物，该药物组合物包含第一活性剂，用于治疗受试者（如癌症）中可从减少SIRPa和CD47之间的信号转导或结合中获益的病症的方法，其中治疗方法包括减少表面有CD47的细胞中QPCTL、QPCT或其组合的表达或酶活性。本发明的化合物和药物组合物可能特别适用于治疗患有涉及 CD47-SIRPa 信号轴的疾病或病症的受试者，例如包括各种癌症类型、动脉粥样硬化、纤维化疾病和传染性疾病。
• 3-HYDR0XY-1,5-DIHYDR0-PYRR0L-2-ONE DERIVATIVES AS INHIBITORS OF GLUTAMINYL CYCLASE FOR THE TREATMENT OF ULCER, CANCER AND OTHER DISEASES
  申请人：Probiodrug AG

  公开号：EP2089383A1

  公开（公告）日：2009-08-19