2-[3-(3H-benzimidazol-5-yl)-2-oxo-1,3-oxazolidin-4-yl]-5-(3,3-difluoropyrrolidin-1-yl)benzonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-[3-(3H-benzimidazol-5-yl)-2-oxo-1,3-oxazolidin-4-yl]-5-(3,3-difluoropyrrolidin-1-yl)benzonitrile
• 化学式: C₂₁H₁₇F₂N₅O₂
• 分子量: 409.4
• InChiKey: WSWSSNBLBWZRHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  85.2
• 氢给体数：
  1
• 氢受体数：
  7

文献信息

• [EN] NOVEL INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS
  申请人：PROBIODRUG AG

  公开号：WO2014140279A1

  公开（公告）日：2014-09-18

  The invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein R1, R2, R3, R4 and R5 are as defined herein, 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.

  该发明涉及一种具有式(I)的化合物或其药用可接受的盐、溶剂合物或多形体，包括其所有重质异构体和立体异构体，其中R1、R2、R3、R4和R5的定义如本文所述，作为谷氨酰环化酶（QC，EC 2.3.2.5）的抑制剂。QC催化N-末端谷氨酸残基向吡咯谷氨酸（5-氧代脯氨酰，pGlu*）的分子内环化，释放氨，并催化N-末端谷氨酸残基向吡咯谷氨酸的分子内环化，释放水。
• 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。
• NOVEL INHIBITORS
  申请人：Probiodrug AG

  公开号：EP2970235A1

  公开（公告）日：2016-01-20
• US9512115B2
  申请人：——

  公开号：US9512115B2

  公开（公告）日：2016-12-06