4(5)-(carboxymethyl)-5(4)-methylimidazole hydrochloride | 60093-52-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4(5)-(carboxymethyl)-5(4)-methylimidazole hydrochloride
• 英文别名: (5-Methyl-1H-imidazol-4-yl)acetic acid hydrochloride；2-(5-methyl-1H-imidazol-4-yl)acetic acid;hydrochloride
• CAS: 60093-52-9
• 化学式: C₆H₈N₂O₂*ClH
• mdl: MFCD28118581
• 分子量: 176.603
• InChiKey: DADBHRWTRQHTTO-UHFFFAOYSA-N

物化性质

• 熔点：
  203.5-204.9 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -1.19
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  66
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲醇 、 4(5)-(carboxymethyl)-5(4)-methylimidazole hydrochloride 在 乙酰氯 作用下， 反应 6.0h， 生成 methyl 2-(4-methyl-1H-imidazol-5-yl)acetate hydrochloride 、 methyl 2-(4-methyl-1H-imidazol-5-yl)acetate hydrochloride
  参考文献：
  名称：

  发现α-取代的咪唑-4-乙酸类似物作为新型一类对视网膜血管音有影响的ρ1γ-氨基丁酸A型受体拮抗剂

  摘要：

  含ρ的γ-氨基丁酸A型受体（GABA A Rs）在控制视觉信号中起重要作用。因此，选择性靶向这些GABA A R的配体是令人关注的。在这项研究中，我们证明了部分GABA A R激动剂咪唑-4-乙酸（IAA）能够在体内穿透血脑屏障。我们制备了一系列的α-和N-烷基化以及IAA的双环类似物，以研究该支架的结构-活性关系，重点是IAA的乙酸侧链。通过IAA制备从化合物升通过有效最小步合成组氨酸，以及它们的药理学性质进行了表征在天然大鼠GABA甲Rs in a [3H]muscimol binding assay and at recombinant human α1β2γ2S and ρ1 GABAARs using the FLIPR™ membrane potential assay. The (+)‐α‐methyl‐ and α‐cyclopropyl‐substituted IAA analogues

  DOI：

  10.1002/cmdc.201600356
• 作为产物：
  描述：

  4-羟甲基-5-甲基咪唑 在 氯化亚砜 、 氢溴酸 作用下， 以 二甲基亚砜 为溶剂， 反应 9.0h， 生成 4(5)-(carboxymethyl)-5(4)-methylimidazole hydrochloride
  参考文献：
  名称：

  5-Substituted Imidazole-4-acetic Acid Analogues:  Synthesis, Modeling, and Pharmacological Characterization of a Series of Novel γ-Aminobutyric Acid_C Receptor Agonists

  摘要：

  A series of ring-substituted analogues of imidazole-4-acetic acid (IAA, 4), a partial agonist at both GABA(A) and GABA(C) receptors (GABA = gamma-aminobutyric acid), have been synthesized. The synthesized compounds 8a-1 have been evaluated as ligands for the alpha(1)beta(2)gamma(2S) GABA(A) receptors and the rho(1) GABA(C) receptors using the FLIPR membrane potential (FMP) assay and by electrophysiology techniques. None of the tested compounds displayed activity at the GABA(A) receptors at concentrations up to 1000 mu M. However, the 5-Me, 5-Ph, 5-p-Me-Ph, and 5-p-F-Ph IAA analogues, 8a,c,f,g, displayed full agonist activities at the rho(1) receptors in the FMP assay (EC50 in the range 22-420 mu M). Ligand-protein docking identified the Thr129 in the alpha(1) subunit and the corresponding Ser168 residue in rho(1) as determinants of the selectivity displayed by the 5-substituted IAA analogues. The fact that GABA, 4, and 8a displayed decreased agonist potencies at a rho(1)Ser168Thr mutant compared to the WT rho(1) receptor strongly supported this hypothesis. However, in contrast to GABA and 4, which exhibited increased agonist potencies at a alpha(1)(Thr129Ser)beta(2)gamma(2) mutant compared to WT GABA(A) receptor, the data obtained for 8a at the WT and mutant receptors were nonconclusive.

  DOI：

  10.1021/jm070447j