SCH79797二盐酸盐 | 1216720-69-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: SCH79797二盐酸盐
• 英文名称: SCH 79797 dihydrochloride
• 英文别名: 3-N-cyclopropyl-7-[(4-propan-2-ylphenyl)methyl]pyrrolo[3,2-f]quinazoline-1,3-diamine;dihydrochloride
• CAS: 1216720-69-2
• 化学式: C23H27Cl2N5
• 分子量: 444.4
• InChiKey: NNJTXSQXGHYXAJ-UHFFFAOYSA-N

物化性质

• 溶解度：
  在乙醇中溶解度为 25 mM，在 DMSO 中溶解度为 50 mM

计算性质

• 辛醇/水分配系数(LogP)：
  5.76
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  68.8
• 氢给体数：
  4
• 氢受体数：
  4

制备方法与用途

生物活性

SCH79797 dihydrochloride 是一种高效的选择性非肽蛋白酶激活受体 1 (PAR1) 拮抗剂。它能够抑制高亲和力的凝血酶受体激活肽与 PAR1 的结合，IC50 值为 70 nM，Ki 为 35 nM。SCH79797 dihydrochloride 还以 IC50 为 3 μM 抑制凝血酶诱导的血小板凝集，并具有抗增殖和促凋亡作用，能够限制大鼠心脏的心肌缺血/再灌注损伤。此外，它还可以有效地阻止血管平滑肌细胞、内皮细胞及星形胶质细胞中的 PAR1 活化。

靶点

Protease activated receptor 1 (PAR1)；凋亡

体外研究

SCH79797 能够以竞争性方式抑制高亲和力凝血酶受体激活肽 ([3H]haTRAP) 结合。它能抑制 α-凝血酶及 haTRAP 引起的人类血小板聚集，但不会抑制由粘连配体激动剂（PAR-4）γ-凝血酶、ADP 或胶原蛋白引起的血小板聚集。SCH79797 有效抑制了凝血酶诱导的胞质游离钙离子 ([Ca2+]i) 浓度增加。它还完全抑制了凝血酶和 TK 刺激下的 [3H]胸腺嘧啶核苷摄取。此外，SCH79797 能以浓度依赖性方式干扰多种人类及小鼠细胞系的生长。在 NIH 3T3、HEK 293 和 A375 细胞中，其半数有效抑制浓度分别为 75 nM、81 nM 和 116 nM。在低浓度时，它能够抑制血清刺激下的 p44/p42 丝裂原活化蛋白激酶 (MAPK) 活性，并在高浓度时诱导细胞凋亡。

体内研究

SCH79797（2.5-250 μg/kg；静脉注射）在大鼠心肌缺血/再灌注损伤模型中，于缺血前或缺血期间给予治疗，可剂量依赖性地减少完整大鼠心脏的梗死面积。最佳剂量为 25 μg/kg。

动物模型	雌性 Sprague Dawley 大鼠（8 周龄），心肌缺血/再灌注损伤
剂量	2.5 μg/kg, 10 μg/kg, 25 μg/kg, 50 μg/kg, 100 μg/kg, 和 250 μg/kg
给药方式	静脉注射
结果	缺血前或缺血期间给予治疗，可减少完整大鼠心脏的梗死面积。

文献信息

• PAR-1 based therapeutic conjugates and uses thereof
  申请人：TEL HASHOMER MEDICAL RESEARCH INFRASTRUCTURE AND SERVICES LTD.

  公开号：US10028999B2

  公开（公告）日：2018-07-24

  The present invention is directed to a peptide conjugate comprising an alpha-amino protecting moiety, a peptide comprising the amino acid sequence at least 3 amino-acid long derived from the C′-terminus of PAR-1, or an active variant thereof and a protease-disabling moiety. The present invention is further directed to pharmaceutical compositions comprising the peptide conjugate and use thereof for treating diseases and disorder associated with excessive PAR-1 activity.

  本发明涉及一种多肽共轭物，该多肽共轭物包含一个α-氨基保护基团、一个包含至少3个氨基酸长的氨基酸序列的多肽，该氨基酸序列来自PAR-1的C′-末端或其活性变体，以及一个蛋白酶抑制基团。本发明进一步涉及包含多肽共轭物的药物组合物及其用于治疗与 PAR-1 活性过高有关的疾病和失调。
• Compounds having antibacterial activity and methods of use
  申请人：The Trustees of Princeton University

  公开号：US11077109B2

  公开（公告）日：2021-08-03

  In one aspect, methods of treating bacterial infections are described herein employing compounds having more than one target for antibacterial activity. Additionally pharmaceutical compositions comprising such compounds are also described.

  在一个方面，本文描述了采用具有一个以上抗菌活性靶点的化合物治疗细菌感染的方法。此外，还描述了包含此类化合物的药物组合物。
• PAR-1 BASED THERAPEUTIC CONJUGATES AND USES THEREOF
  申请人：Tel Hashomer Medical Research Infrastructure and Services Ltd.

  公开号：EP3143036A1

  公开（公告）日：2017-03-22
• COMPOUNDS HAVING ANTIBACTERIAL ACTIVITY AND METHODS OF USE
  申请人：The Trustees of Princeton University

  公开号：US20190201401A1

  公开（公告）日：2019-07-04

  In one aspect, methods of treating bacterial infections are described herein employing compounds having more than one target for antibacterial activity. Additionally pharmaceutical compositions comprising such compounds are also described.
• Method Of Selecting Stem Cells Having Ability To Produce Extracellular Vesicles With High Efficiency Using Activation Of Protease-Activated Receptor-Mediated Signaling Pathways
  申请人：SAMSUNG LIFE PUBLIC WELFARE FOUNDATION

  公开号：US20210255169A1

  公开（公告）日：2021-08-19

  The present disclosure relates to a method of selecting stem cells having the ability to produce extracellular vesicles with high efficiency, the method including the step of measuring the activity of protease-activated receptor (PAR)-mediated signaling pathways, stem cells selected by the method, and a method of screening an inducer for the production of extracellular vesicles. According to the present disclosure, upon treatment of stem cells with thrombin, the production of extracellular vesicles in the stem cells and the levels of proteins in the extracellular vesicles are significantly increased via PAR-mediated signaling pathways, and thus stem cells having the ability to produce extracellular vesicles with high efficiency can be efficiently selected by treating stem cells with thrombin and measuring an activation level of a PAR-mediated signaling pathway, and stem cells selected by this method can be effectively used in related research and clinical fields.