7-amino-5-dimethylamino-2-(2-furyl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazine | 139179-90-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 7-amino-5-dimethylamino-2-(2-furyl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazine
• 英文别名: 2-(furan-2-yl)-5-N,5-N-dimethyl-[1,2,4]triazolo[1,5-a][1,3,5]triazine-5,7-diamine
• CAS: 139179-90-1
• 化学式: C₁₀H₁₁N₇O
• 分子量: 245.244
• InChiKey: NKEUCELRWWKAGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  二苯基乙酰氯 、 7-amino-5-dimethylamino-2-(2-furyl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazine 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以70%的产率得到5-dimethylamino-7-diphenylacetylamino-2-(2-furyl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazine
  参考文献：
  名称：

  Synthesis and pharmacological characterization of a new series of 5,7-disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand–receptor recognition process

  摘要：

  A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3-96.5 nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA3 AR (range 311-633 nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA2B AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC50 3.42 mu M) and could represent a starting point for searching new non-xanthine hA2B AR antagonists. Molecular models of the rA(2A) and hA3 ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor-driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.02.039
• 作为产物：
  描述：

  二甲胺 、 7-amino-2-(furan-2-yl)-5-phenoxy-[1,2,4]triazolo[1,5-a][1,3,5]triazine 以 乙醇 为溶剂， 反应 4.0h， 以80%的产率得到7-amino-5-dimethylamino-2-(2-furyl)-[1,2,4]triazolo[1,5-a]-[1,3,5]triazine
  参考文献：
  名称：

  Synthesis and pharmacological characterization of a new series of 5,7-disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand–receptor recognition process

  摘要：

  A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3-96.5 nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA3 AR (range 311-633 nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA2B AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC50 3.42 mu M) and could represent a starting point for searching new non-xanthine hA2B AR antagonists. Molecular models of the rA(2A) and hA3 ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor-driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.02.039

文献信息

• NON BRAIN PENETRANT A2A INHIBITORS AND METHODS FOR USE IN THE TREATMENT OF CANCERS
  申请人：ITEOS THERAPEUTICS S.A.

  公开号：US20200102319A1

  公开（公告）日：2020-04-02

  The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention further relates to the use of the compounds of Formula (I) as A2A inhibitors. The invention also relates to the use of the compounds of Formula (I) for the treatment and/or prevention of proliferative disorders, including cancers.

  本发明涉及式（I）的化合物或其药用可接受盐。该发明进一步涉及将式（I）的化合物用作A2A抑制剂。该发明还涉及将式（I）的化合物用于治疗和/或预防增殖性疾病，包括癌症。
• [EN] SULFONAMIDE COMPOUNDS TARGETING CD73 AND ADENOSINE RECEPTORS<br/>[FR] COMPOSÉS DE SULFONAMIDE CIBLANT CD73 ET LES RÉCEPTEURS D'ADÉNOSINE
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2021105916A1

  公开（公告）日：2021-06-03

  The present invention relates to bispecific compound of formula (I) as dual inhibitors of CD73 and adenosine receptors. The present invention also relates to pharmaceutical compositions comprising said compounds or a pharmaceutically acceptable salt or a stereoisomer or a prodrug thereof and use of such compounds in the treatment of diseases mediated by CD73 and/or adenosine receptors, particularly A2aR or A2bR.

  本发明涉及一种具有如下式(I)的双特异性化合物，作为CD73和腺苷受体的双重抑制剂。本发明还涉及包含所述化合物或其药用可接受盐或立体异构体或前药的药物组合物，以及在治疗由CD73和/或腺苷受体介导的疾病中使用这些化合物，特别是A2aR或A2bR。
• Azole Derivatives
  申请人：ZENECA LIMITED

  公开号：EP0459702A1

  公开（公告）日：1991-12-04

  The invention concerns novel, pharmaceutically useful compounds of formula I in which Q is a 5-membered heteroaryl optionally bearing 1 or 2 substituents independently selected from (1-4C)alkyl and halogeno ; R1 is hydrogen, (1-6C)alkyl, or (1-4C)alkanoyl ; R2 (when not as hereinbelow defined together with X) is hydrogen, (3-12C)cycloalkyl, (3-6C)alkenyl, phenyl(3-6C)alkenyl, tetrafluorophenyl, pentafluorophenyl, 5- or 6-membered heteroaryl, optionally substituted (1-6C)alkyl or optionally substituted phenyl ; X is oxy, thio, sulphinyl, sulphonyl or an imino group of formula -NRa- in which Ra is hydrogen, (1-6C)alkyl or together with R2 and the adjacent nitrogen atom forms a 4 to 6-membered saturated heterocyclic ring ; and A is N or CT in which T is hydrogen or (1-4C)alkyl ; or a pharmaceutically acceptable salt thereof ; processes for the manufacture of the compounds and pharmaceutical compositions containing them. The compounds are useful as adenosine antagonists. The invention further provides novel intermediates useful in the manufacture of the compounds of formula I.

  本发明涉及式 I 的新型药用化合物，其中 Q 是 5 元杂芳基，任选带有 1 或 2 个独立选自 (1-4C)烷基和卤素的取代基；R1 是氢、(1-6C)烷基或 (1-4C)alkanoyl ；R2（当不与 X 一起定义时）是氢、(3-12C)环烷基、(3-6C)烯基、苯基(3-6C)烯基、四氟苯基、五氟苯基、5 或 6 元杂芳基、任选取代的(1-6C)烷基或任选取代的苯基；X 是氧、硫代、亚砜基、磺酰基或式 -NRa- 的亚氨基，其中 Ra 是氢、(1-6C)烷基或与 R2 和邻近的氮原子一起形成 4 至 6 元饱和杂环；以及 A 是 N 或 CT，其中 T 是氢或 (1-4C)烷基；或其药学上可接受的盐；化合物的制造工艺和含有这些化合物的药物组合物。这些化合物可用作腺苷拮抗剂。本发明进一步提供了用于制造式 I 化合物的新型中间体。
• US5270311A
  申请人：——

  公开号：US5270311A

  公开（公告）日：1993-12-14
• US5356894A
  申请人：——

  公开号：US5356894A

  公开（公告）日：1994-10-18