2-(2-呋喃基)-7-[3-(4-甲氧基苯基)丙基]-7H-吡唑并[4,3-e][1,2,4]噻唑并[1,5-c]嘧啶-5-胺 | 316173-57-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 中文名称: 2-(2-呋喃基)-7-[3-(4-甲氧基苯基)丙基]-7H-吡唑并[4,3-e][1,2,4]噻唑并[1,5-c]嘧啶-5-胺
• 中文别名: 2-(2-呋喃基)-7-[3-(4-甲氧苯基)丙基]-7H-吡唑并[4,3-E][1,2,4]三唑并[1,5-C]嘧啶-5-胺
• 英文名称: 7-(3-(4-methoxyphenyl)propyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine-5-amine
• 英文别名: Sch 442416；2-(2-furanyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine；2-(2-furyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine；2-(Furan-2-yl)-7-(3-(4-methoxyphenyl)propyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine；4-(furan-2-yl)-10-[3-(4-methoxyphenyl)propyl]-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaen-7-amine
• CAS: 316173-57-6
• 化学式: C₂₀H₁₉N₇O₂
• 分子量: 389.417
• InChiKey: AEULVFLPCJOBCE-UHFFFAOYSA-N

物化性质

• 密度：
  1.49±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

SCH-442416 是一种选择性腺苷 A2A 受体拮抗剂，与人和大鼠腺苷 A2A 受体结合的 Ki 值分别为 0.048 nM 和 0.5 nM。

靶点

Target	Value
Human A2A receptor (Cell-free assay)	0.048 nM(Ki)
Rat A2A receptor (Cell-free assay)	0.5 nM(Ki)

反应信息

• 作为反应物：
  描述：

  2-(2-呋喃基)-7-[3-(4-甲氧基苯基)丙基]-7H-吡唑并[4,3-e][1,2,4]噻唑并[1,5-c]嘧啶-5-胺 在 水 、 三溴化硼 、 caesium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 2-(4-(3-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)propyl)phenoxy)acetic acid
  参考文献：
  名称：

  Molecular probes for the A2A adenosine receptor based on a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold

  摘要：

  Pyrazolo[4,3-e][1,2,4] triazolo[1,5-c]pyrimidin-5-amine derivatives such as SCH 442416 display high affinity and selectivity as antagonists for the human A(2A) adenosine receptor (AR). We extended ether-linked chain substituents at the p-position of the phenyl group using optimized O-alkylation. The conjugates included an ester, carboxylic acid and amines (for amide condensation), an alkyne (for click chemistry), a fluoropropyl group (for F-18 incorporation), and fluorophore reporter groups (e. g., BODIPY conjugate 14, K-i 15 nM). The potent and A(2A)AR-selective N-aminoethylacetamide 7 and N-[2-(2-aminoethyl)-aminoethyl]acetamide 8 congeners were coupled to polyamidoamine (PAMAM) G3.5 dendrimers, and the multivalent conjugates displayed high A(2A)AR affinity. Theoretical docking of an AlexaFluor conjugate to the receptor X-ray structure highlighted the key interactions between the heterocyclic core and the binding pocket of the A(2A)AR as well as the distal anchoring of the fluorophore. In conclusion, we have synthesized a family of high affinity functionalized congeners as pharmacological probes for studying the A(2A)AR. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.11.082
• 作为产物：
  描述：

  1-(3-氯丙基)-4-甲氧基苯 在 N-甲基吡咯烷酮 、 盐酸 、 对甲苯磺酸 、 三乙胺 、 肼 作用下， 以 1,4-二氧六环 、 二苯醚 、 乙醇 、 乙二醇甲醚 为溶剂， 反应 110.5h， 生成 2-(2-呋喃基)-7-[3-(4-甲氧基苯基)丙基]-7H-吡唑并[4,3-e][1,2,4]噻唑并[1,5-c]嘧啶-5-胺
  参考文献：
  名称：

  Design, Radiosynthesis, and Biodistribution of a New Potent and Selective Ligand for in Vivo Imaging of the Adenosine A_2A Receptor System Using Positron Emission Tomography

  摘要：

  DOI：

  10.1021/jm0009843

文献信息

• Bitopic fluorescent antagonists of the A_2A adenosine receptor based on pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine functionalized congeners
  作者：Romain Duroux、Antonella Ciancetta、Philip Mannes、Jinha Yu、Shireesha Boyapati、Elizabeth Gizewski、Said Yous、Francisco Ciruela、John A. Auchampach、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1039/c7md00247e

  日期：——

  Functionalized antagonist probes of the A_2A adenosine receptor.

  A_2A腺苷受体的功能化拮抗探针。
• Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A2A receptor-selective antagonists
  作者：Bidhan A. Shinkre、T. Santhosh Kumar、Zhan-Guo Gao、Francesca Deflorian、Kenneth A. Jacobson、William C. Trenkle

  DOI：10.1016/j.bmcl.2010.08.021

  日期：2010.10

  Movement disorders such as Parkinson’s disease and Huntington’s disease are serious life-limiting and debilitating movement disorders. Their onset typically occurs from mid-life to late in life, and effective diagnostic techniques for detecting and following the disease course are lacking. Our goal is to develop receptor imaging agents for positron emission tomography (PET) that selectively target

  帕金森病和亨廷顿病等运动障碍是严重的限制生命和使人衰弱的运动障碍。它们的发病通常发生在中年至晚年，并且缺乏用于检测和跟踪病程的有效诊断技术。我们的目标是开发用于正电子发射断层扫描 (PET) 的受体显像剂，它选择性地靶向在纹状体中高度表达的最相关的腺苷受体 (AR) 亚型，即 A 2A AR。为了进一步实现这一目标，我们已经合成并在药理学上表征了一系列高亲和力 A 2A AR 配体，基于已知的拮抗剂 SCH 442416 (R = -Me)，其末端具有结构可变性 (R = -Et, -一世-Pr、-allyl 等）。适合用作PET示踪剂的O-氟乙基类似物的K i值为12.4 nM，并且与A 1和A 3 AR相比对A 2A AR具有高度选择性。
• [EN] PROCESS AND INTERMEDIATES FOR THE PREPARATION OF PRELADENANT AND RELATED COMPOUNDS<br/>[FR] PROCÉDÉ ET INTERMÉDIAIRES POUR LA PRÉPARATION DU PRÉLADENANT ET COMPOSÉS ASSOCIÉS
  申请人：MAPI PHARMA LTD

  公开号：WO2012127472A1

  公开（公告）日：2012-09-27

  The present invention describes processes for the synthesis of 2-(furan-2-yl)-7-[2-[4-[4-(2-methoxyethoxy)phenyl]piperazin-l-yl] ethyl]-7H-pyrazolo[ 4,3-e ][1,2,4]- triazolo[1,5c] pyrimidin-5-amine (Preladenant) represented by the structure of formula (1 ), and solvates and salts thereof, especially salts with pharmaceutically acceptable acids. The process of the present invention is useful not only for Preladenant production, but also for the preparation of other biologically active compounds of general formula (17), such as A2a receptor antagonists used for the treatment of central nervous system diseases, among others. The present invention further relates to certain intermediates formed in such processes.

  本发明描述了合成2-(呋喃-2-基)-7-[2-[4-[4-(2-甲氧基乙氧基)苯基]哌嗪-1-基]乙基]-7H-吡唑并[4,3-e][1,2,4]-三唑[1,5c]嘧啶-5-胺（Preladenant）的方法，其结构式表示为（1），以及其溶剂化物和盐，尤其是与药用可接受酸的盐。本发明的方法不仅对Preladenant的生产有用，而且对于制备一般式（17）的其他生物活性化合物也有用，例如用于治疗中枢神经系统疾病的A2a受体拮抗剂等。本发明还涉及在这些过程中形成的某些中间体。
• 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。
• Microparticle formulations of adenosine receptor antagonists for treating cancer
  申请人：Phosphorex, Inc.

  公开号：US10702476B2

  公开（公告）日：2020-07-07

  The invention provides compositions comprising microparticles wherein the microparticles comprise at least one adenosine 2a receptor antagonist (A2ARA), at least one pharmaceutically acceptable polymer and at least one pharmaceutically acceptable negatively charged agent wherein the microparticles optionally have a highly negative zeta potential of less than about −40 mV. The invention also provides pharmaceutical compositions of the microparticles of the invention and methods of using the compositions of the invention to enhance an immune response in a patient in need thereof and as anti-cancer immunotherapy.

  本发明提供了包含微颗粒的组合物，其中微颗粒包含至少一种腺苷2a受体拮抗剂(A2ARA)、至少一种药学上可接受的聚合物和至少一种药学上可接受的负电荷剂，其中微颗粒可选地具有小于约-40 mV的高负zeta电位。本发明还提供了本发明微粒的药物组合物以及使用本发明组合物增强有需要的患者的免疫反应和作为抗癌免疫疗法的方法。