3-(3,4-Dimethoxy-phenyl)-10-methyl-10H-benzo[4,5]imidazo[2,1-c][1,2,4]triazin-4-one | 257955-59-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3,4-Dimethoxy-phenyl)-10-methyl-10H-benzo[4,5]imidazo[2,1-c][1,2,4]triazin-4-one
• 英文别名: 3-(3,4-Dimethoxyphenyl)-10-methyl-[1,2,4]triazino[4,3-a]benzimidazol-4-one
• CAS: 257955-59-2
• 化学式: C₁₈H₁₆N₄O₃
• 分子量: 336.35
• InChiKey: RDHMAUFMGHQLHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3,4-Dimethoxy-phenyl)-10-methyl-10H-benzo[4,5]imidazo[2,1-c][1,2,4]triazin-4-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以67%的产率得到3-(3,4-Dihydroxy-phenyl)-10-methyl-10H-benzo[4,5]imidazo[2,1-c][1,2,4]triazin-4-one
  参考文献：
  名称：

  3-Aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones:  A New Class of Selective A₁ Adenosine Receptor Antagonists

  摘要：

  Radioligand binding assays using bovine cortical membrane preparations and biochemical in vitro studies revealed that various 3-aryl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one (ATBI) derivatives, previously reported by us as ligands of the central benzodiazepine receptor (BzR) (Primofiore, G.; et al. J. Med. Chem. 2000, 43, 96-102), behaved as antagonists at the Al adenosine receptor (A(1)AR). Alkylation of the nitrogen at position 10 of the triazinobenzimidazole nucleus conferred selectivity for the A(1)AR vs the BzR. The most potent ligand of the ATBI series (10-methyl-3-phenyl[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-one 12) displayed a K-i value of 63 nM at the A(1)AR without binding appreciably to the adenosine A(2A) and A(3) nor to the benzodiazepine receptor. Pharmacophore-based modeling studies in which 12 was compared against a set of well-established A(1)AR antagonists suggested that three hydrogen bonding sites (HB1 acceptor, HB2 and HB3 donors) and three lipophilic pockets (L1, L2, and L3) might be available to antagonists within the A1AR binding cleft. According to the proposed pharmacophore scheme, the lead compound 12 engages interactions with the HB2 site (via the N2 nitrogen) as well as with the L2 and L3 sites (through the pendant and the fused benzene rings). The results of these studies prompted the replacement of the methyl with more lipophilic groups at the 10-position (to fill the putative L1 lipophilic pocket) as a strategy to improve A1AR affinity. Among the new compounds synthesized and tested, the 3,10-diphenyl[1,2,4]triazino[4,3-a]benzimidazol-4( 10H)-one (23) was characterized by a K-i value of 18 nM which represents a 3.5-fold gain of A(1)AR affinity compared with the lead 12. A rhodopsin-based model of the bovine adenosine A(1)AR was built to highlight the binding mode of 23 and two well-known A(1)AR antagonists (III and VII) and to guide future lead optimization projects. In our docking simulations, 23 receives a hydrogen bond (via the N1 nitrogen) from the side chain of Asn247 (corresponding to the HB1 and HB2 sites) and fills the L1, L2, and L3 lipophilic pockets with the 10-phenyl, 3-phenyl, and fused benzene rings, respectively.

  DOI：

  10.1021/jm001054m
• 作为产物：
  描述：

  (3,4-二甲氧基苯基)-乙醛酸 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 3-(3,4-Dimethoxy-phenyl)-10-methyl-10H-benzo[4,5]imidazo[2,1-c][1,2,4]triazin-4-one
  参考文献：
  名称：

  3-芳基-[1,2,4]三嗪并[4,3-a]苯并咪唑-4（10H）-ones：三环杂芳族衍生物，是一类新的苯并二氮杂receptor受体配体。

  摘要：

  制备了一系列3-取代的[1,2,4]三嗪[4,3-c]苯并咪唑V，并在中央苯并二氮杂pine受体（BzR）上进行了测试。这些化合物被设计为先前描述的N-苄基吲哚基二烯丙基乙二酰胺衍生物IV的刚性类似物。标题化合物V显示出亲和力，该亲和力直接取决于N（10）-H基团和位置3上的芳环的存在。相对于吲哚基二羟乙酰胺，它们中的一些引起了2倍或3倍的高亲和力。导数IV（R = H）。GABA比和[（35）S]-叔丁基环磷酸硫代酸酯结合数据揭示了化合物1c，e，f，j，k的部分反向激动剂/拮抗剂和2c的部分激动剂的功效谱。该最后的化合物被证明可有效拮抗戊四氮诱导的小鼠癫痫发作。

  DOI：

  10.1021/jm991131h