4-二苯基甲氧基-1-[3-(1H-四唑)丙基]-哌啶 | 162641-16-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-二苯基甲氧基-1-[3-(1H-四唑)丙基]-哌啶
• 中文别名: 4-(二苯基甲氧基)-1-[3-(2H-四氮唑-5-基)丙基]哌啶
• 英文名称: 4-(diphenylmethoxy)-1-[3-(2H-tetrazol-5-yl)propyl]piperidine
• 英文别名: HQL-79；4-(Benzhydryloxy)-1-[3-(1H-tetraazol-5-YL)propyl]piperidine；4-benzhydryloxy-1-[3-(2H-tetrazol-5-yl)propyl]piperidine
• CAS: 162641-16-9
• 化学式: C₂₂H₂₇N₅O
• mdl: MFCD00936179
• 分子量: 377.489
• InChiKey: TZQGXAHOROZEKN-UHFFFAOYSA-N

物化性质

• 沸点：
  553.6±60.0 °C(Predicted)
• 密度：
  1.21
• 溶解度：
  DMSO：可溶，2mg/mL，澄清（加热）

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.409
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

生物活性

HQL-79 是一种有效、选择性且可口服的人造血前列腺素 D 合成酶（hematopoietic prostaglandin D synthase, H-PGDS）抑制剂，能够高度选择性地抑制 PGD2 的合成。它是一种抗过敏剂，对 H-PGDS 的 Kd 值为 0.8 μM，IC50 值为 6 μM，并且不对 COX-1、COX-2、m-PGES 或 L-PGDS 等产生作用。

靶点

• IC50: 6 μM (H-PGDS)
• Kd: 0.8 μM (H-PGDS)

体外研究

HQL-79 是 PGH2 的竞争性抑制剂，同时对 GSH 起非竞争性抑制作用。

文献信息

• MULTIHETEROARYL COMPOUNDS AS INHIBITORS OF H-PGDS AND THEIR USE FOR TREATING PROSTAGLANDIN D2 MEDIATED DISEASES
  申请人：Endres Gregory W.

  公开号：US20100075990A1

  公开（公告）日：2010-03-25

  Multiheteroaryl compounds, their preparation, pharmaceutical compositions comprising these compounds, and their pharmaceutical use in the prevention and treatment of prostaglandin D 2 mediated diseases and conditions that may be modulated by the inhibition of hematopoietic prostaglandin D synthase (H-PGDS).

  多杂环芳基化合物，它们的制备，包括这些化合物的药物组合物，以及它们在预防和治疗可能通过抑制造血前列腺素D合成酶（H-PGDS）调节的前列腺素D2介导的疾病和症状中的药用。
• METHOD FOR ASSAYING COMPOUNDS OR AGENTS FOR ABILITY TO DISPLACE POTENT LIGANDS OF HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE
  申请人：Maxey Kirk W.

  公开号：US20090286261A1

  公开（公告）日：2009-11-19

  An exemplary embodiment may be directed to a fluorescence polarization assay that screens compounds or agents for their affinity to hematopoietic prostaglandin D synthase (H-PGDS) based on their ability to displace a fluorophore-containing detection analyte bound to an enzyme comprising the primary amino acid sequence of H-PGDS. Another exemplary embodiment utilizes an enzyme having a maltose binding protein amino-acid sequence fused with an N-terminus of the enzyme.

  一个示范性实施例可能涉及一种荧光极化测定法，该方法通过检测化合物或试剂对血液造血素D合成酶（H-PGDS）的亲和力来筛选，其基于它们能够将结合到具有H-PGDS主要氨基酸序列的酶上的含荧光团的检测分析物位移开。另一个示范性实施例利用具有麦芽糖结合蛋白氨基酸序列的酶，与酶的N-末端融合。
• DRUGS FOR IMPROVING THE PROGNOSIS OF BRAIN INJURY AND A METHOD OF SCREENING THE SAME
  申请人：Japan Science and Technology Agency

  公开号：EP1535629A1

  公开（公告）日：2005-06-01

  There are provided a compound for treatment or prevention of brain injury caused by diseases such as cerebrovascular disorder, brain degenerative disease and demyelinating disease and a method for screening the same. Brain injury in which prostaglandin D2 is participated is treated or prevented by inhibition of hematopoietic prostaglandin D synthase induced in microglia cell or macrophage of brain injury area by diseases such as cerebrovascular disorder, brain degenerative disease or demyelinating disease or by inhibition of activation of prostaglandin D receptor expressed in astroglia cell around the injured area. There is also provided a method of testing those pharmaceutical substances using a transgenic mouse in which human hematopoietic prostaglandin D synthase is expressed in large amounts.

  提供了一种用于治疗或预防脑血管疾病、脑变性疾病和脱髓鞘疾病等疾病引起的脑损伤的化合物及其筛选方法。 通过抑制脑血管疾病、脑变性疾病或脱髓鞘疾病等疾病在脑损伤区域的小胶质细胞或巨噬细胞中诱导的造血前列腺素 D 合成酶，或通过抑制损伤区域周围星形胶质细胞中表达的前列腺素 D 受体的活化，治疗或预防前列腺素 D2 参与的脑损伤。此外，还提供了一种利用大量表达人造血前列腺素 D 合酶的转基因小鼠检测这些药物的方法。
• Drugs for improving prognosis of brain injury
  申请人：Japan Science and Technology Agency

  公开号：EP1598065A2

  公开（公告）日：2005-11-23

  A compound for treatment or prevention of brain injury caused by diseases such as cerebrovascular disorder, brain degenerative disease and demyelinating disease. The compound comprises an antagonist for the prostaglandin D receptor as an effective ingredient. Brain injury in which prostaglandin D2 is a factor is treated or prevented by inhibition of hematopoietic prostaglandin D synthase induced in microglia cell or macrophage of brain area by diseases such as cerebrovascular disorder, brain degenerative disease or demyelinating disease or by inhibition of activation of prostaglandin D receptor expressed in astroglia cell around the injured area.

  一种化合物，用于治疗或预防由脑血管疾病、脑变性疾病和脱髓鞘疾病等疾病引起的脑损伤。该化合物的有效成分包括前列腺素 D 受体拮抗剂。 通过抑制脑血管疾病、脑变性疾病或脱髓鞘疾病等疾病在脑区小胶质细胞或巨噬细胞中诱导的造血前列腺素 D 合成酶，或通过抑制损伤区周围星形胶质细胞中表达的前列腺素 D 受体的活化，治疗或预防以前列腺素 D2 为因素的脑损伤。
• METHOD FOR DETECTING MUSCLE DEGENERATIVE DISEASES, AND METHOD FOR DETERMINING THERAPEUTIC EFFICACY ON THE DISEASES
  申请人：Osaka Bioscience Institute

  公开号：EP2407784A1

  公开（公告）日：2012-01-18

  Muscle degenerative diseases can be detected in the early stage and the therapeutic efficacy of a therapeutic agent and/or a therapy method for the diseases can be determined by measuring 11,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (referred to as "Tetranor-PGDM", hereinbelow) in a sample isolated from a subject.

  通过测量从受试者体内分离出的样本中的 11,15-二氧代-9α-羟基-2,3,4,5-四去氧孕甾-1,20-二酸（以下简称 "四去氧孕甾-PGDM"），可以在早期阶段检测出肌肉退行性疾病，并确定治疗剂和/或治疗方法的疗效。