4-羟基-N-(4-甲氧基-7-吗啉苯并[d]噻唑-2-基)-4-甲基哌啶-1-羧酰胺 | 870070-55-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 4-羟基-N-(4-甲氧基-7-吗啉苯并[d]噻唑-2-基)-4-甲基哌啶-1-羧酰胺
• 中文别名: 4-羟基-N-[4-甲氧基-7-(4-吗啉基)-2-苯并噻唑基]-4-甲基-1-哌啶甲酰胺
• 英文名称: Tozadenant
• 英文别名: SYN-115；4-hydroxy-4-methyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide；4-hydroxy-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide；4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)-4-methylpiperidine-1-carboxamide
• CAS: 870070-55-6
• 化学式: C₁₉H₂₆N₄O₄S
• 分子量: 406.506
• InChiKey: XNBRWUQWSKXMPW-UHFFFAOYSA-N

物化性质

• 密度：
  1.374
• 溶解度：
  不溶于乙醇；不溶于水； ≥20.35 mg/mL，溶于 DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  2-8°C，干燥密封保存。

制备方法与用途

Tozadenant (SYN-115) 是一种腺苷 A2A 受体拮抗剂，能够在人类和恒河猴的 A2A 受体上发挥作用，其 Ki 值分别为 11.5 nM 和 6 nM。

反应信息

• 作为产物：
  描述：

  4-甲氧基-7-吗啉苯并[d]噻唑-2-胺 在 吡啶 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 反应 16.58h， 生成 4-羟基-N-(4-甲氧基-7-吗啉苯并[d]噻唑-2-基)-4-甲基哌啶-1-羧酰胺
  参考文献：
  名称：

  Tozadenant类似物作为腺苷A 2A受体配体的设计，合成和生物学评估

  摘要：

  其目的以获得有力的腺苷A 2A受体（A 2A R）的配体，一系列的4-羟基衍生物18的ñ - （4-甲氧基-7-吗啉-4-基-1,3-苯并[ d ]设计并合成了噻唑-2-基）-4-甲基哌啶-1-羧酰胺（SYN-115，Tozadenant）。通过化学结构原理获得目标化合物，该原理涉及适当的氨基苯并噻唑苯基氨基甲酸酯与市售或易于合成的官能化哌啶的反应。使用放射性配体结合测定法测定它们对人腺苷A 1和A 2A受体的亲和力和亚型选择性。A人的K i值2A R范围从2.4到38 nM，对所有评估的化合物的A 1受体选择性超过120倍，除了13k的K i为361 nM和18倍选择性。最有效的含氟衍生物13e，13g和13l对人A 2A R的K i值分别为4.9 nM，3.6 nM和2.8 nM 。有趣的是，发现大鼠A 2A R的相应值是其四到五倍。更高。通过与18 F放射性标记并在体外进一步证实了它们与A

  DOI：

  10.1016/j.ejmech.2021.113214

文献信息

• Fluorinated Adenosine A_2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics
  作者：Gengyang Yuan、Tanner C. Jankins、Christopher G. Patrick、Phaethon Philbrook、Olivia Sears、Stephen Hatfield、Michail Sitkovsky、Neil Vasdev、Steven H. Liang、Mary Jo Ondrechen、Michael P. Pollastri、Graham B. Jones

  DOI：10.1155/2017/4852537

  日期：2017.10.19

  Antagonism of the adenosine receptor on T cells blocks the hypoxia-adenosinergic pathway to promote tumor rejection. Using an in vivo immunoassay based on the Concanavalin A mouse model, a series of antagonists were studied and identified preladenant as a potent lead compound for development. Molecular modeling was employed to assist drug design and subsequent synthesis of analogs and those of tozadenant

  T细胞上腺苷受体的拮抗作用可阻断缺氧腺苷能途径，从而促进肿瘤排斥。使用基于伴刀豆球蛋白A小鼠模型的体内免疫分析方法，研究了一系列拮抗剂，并确定了preladenant是有效的潜在先导化合物，可用于开发。采用分子建模来辅助药物设计和随后合成类似物和托扎定的化合物，包括氟化聚乙二醇PEG化衍生物。使用两次体外功能性生物测定法评估了类似物的功效，并确认了化合物29（一种预合成的氟化三甘醇衍生物）被确认为潜在的免疫治疗剂。
• 4-Hydroxy-4-methyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide
  申请人：Flohr Alexander

  公开号：US20050261289A1

  公开（公告）日：2005-11-24

  The present invention relates to the compound of formula which is 4-hydroxy-4-methyl-piperidine-1-carboxylic acid(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide, and to pharmaceutically acceptable acid addition salts thereof. It has been found that the compound is useful for the treatment or prevention of Alzheimer's disease, Parkinson's disease, Huntington's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, ADHD (attention deficit hyper-activity disorder), drug addiction to amphetamines, cocaine, opioids, ethanol, nicotine, or cannabinoids, or for the treatment of asthma, allergic responses, hypoxia, ischemia, seizure, substance abuse, or for use as muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardioprotective agents.

  本发明涉及公式的化合物，该化合物为4-羟基-4-甲基-哌啶-1-羧酸(4-甲氧基-7-吗啡啶-4-基苯并噻唑-2-基)-酰胺，以及其药学上可接受的酸盐。已发现该化合物可用于治疗或预防阿尔茨海默病、帕金森病、亨廷顿病、神经保护、精神分裂症、焦虑、疼痛、呼吸功能障碍、抑郁症、注意力缺陷多动障碍(ADHD)、安非他命、可卡因、阿片类、乙醇、尼古丁或大麻素药物成瘾的治疗，或用于哮喘、过敏反应、低氧、缺血、癫痫、物质滥用，或用作肌肉松弛剂、抗精神病药、抗癫痫药、抗惊厥药和心脏保护剂。
• [EN] 4-HYDROXY-4-METHYL-PIPERIDINE-1-CARBOXYLIC ACID (4-METHOXY-7-MORPHOLIN-4-YL-BENZOTHIAZOL-2-YL)-AMIDE<br/>[FR] ACIDE 4-HYDROXY-4-METHYL-PIPERIDINE-1-CARBOXYLIQUE (4-METHOXY-7-MORPHOLIN-4-YL-BENZOTHIAZOL-2-YL)-AMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005116026A1

  公开（公告）日：2005-12-08

  The present invention relates to the compound of formula (I): which is 4-hydroxy-4-methyl-piperidine-l-carboxylic acid (4-methoxy-7-morpholin-4­-yl-benzothiazol-2-yl)-amide, and pharmaceutically acceptable acid addition salts thereof. It has been found that the compound is useful for the treatment or prevention of Alzheimer's disease, Parkinson's disease, Huntington's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, ADHD ( attention deficit hyper-activity disorder), drug addiction to amphetamines, cocaine, opioids, ethanol, nicotine, cannabinoids, or for the treatment of asthma, allergic responses, hypoxia, ischemia, seizure, substance abuse, or for use as muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardioprotective agents.

  本发明涉及式（I）的化合物：4-羟基-4-甲基-哌啶-1-羧酸（4-甲氧基-7-吗啉-4-基苯并噻唑-2-基）-酰胺及其药学上可接受的酸加盐。已经发现该化合物可用于治疗或预防阿尔茨海默病、帕金森病、亨廷顿病、神经保护、精神分裂症、焦虑、疼痛、呼吸功能障碍、抑郁症、注意力缺陷多动障碍（ADHD）、物质成瘾（安非他命、可卡因、阿片类、乙醇、尼古丁、大麻素）或用于治疗哮喘、过敏反应、缺氧、缺血、癫痫、物质滥用，或用作肌肉松弛剂、抗精神病药物、抗癫痫药物、抗惊厥药物和心脏保护剂。
• 4-hydroxy-4-methyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide
  申请人：Hoffmann-La Roche Inc.

  公开号：US07368446B2

  公开（公告）日：2008-05-06

  The present invention relates to the compound of formula which is 4-hydroxy-4-methyl-piperidine-1-carboxylic acid(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide, and to pharmaceutically acceptable acid addition salts thereof. It has been found that the compound is useful for the treatment or prevention of Alzheimer's disease, Parkinson's disease, Huntington's disease, neuroprotection, schizophrenia, anxiety, pain, respiration deficits, depression, ADHD (attention deficit hyper-activity disorder), drug addiction to amphetamines, cocaine, opioids, ethanol, nicotine, or cannabinoids, or for the treatment of asthma, allergic responses, hypoxia, ischemia, seizure, substance abuse, or for use as muscle relaxants, antipsychotics, antiepileptics, anticonvulsants and cardioprotective agents.

  本发明涉及式为4-羟基-4-甲基哌啶-1-羧酸(4-甲氧基-7-吗啉-4-基苯并噻唑-2-基)-酰胺及其药学上可接受的酸加盐。已发现该化合物可用于治疗或预防阿尔茨海默病、帕金森病、亨廷顿病、神经保护、精神分裂症、焦虑、疼痛、呼吸功能障碍、抑郁症、注意力缺陷多动障碍、安非他命、可卡因、阿片类、乙醇、尼古丁或大麻素类药物成瘾的治疗，或用于哮喘、过敏反应、低氧、缺血、癫痫、物质滥用，或用作肌肉松弛剂、抗精神病药、抗癫痫药、抗惊厥药和心脏保护剂。
• Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS
  申请人：Yeda Research and Development Co. Ltd

  公开号：US10618963B2

  公开（公告）日：2020-04-14

  The present specification discloses a pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS. The pharmaceutical composition is administered by a dosage regimen comprising at least one course of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session of non-treatment.

  本说明书公开了一种药物组合物，该药物组合物包含一种活性剂，可降低个体的全身免疫抑制水平，用于治疗中枢神经系统的疾病、紊乱、病症或损伤。该药物组合物通过一个剂量方案给药，该剂量方案包括至少一个疗程，每个疗程依次包括一个治疗疗程和一个非治疗间隔疗程。