4(5)-(carboxymethyl)-2-phenylimidazole hydrochloride | 110356-17-7

• 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)-2-phenylimidazole hydrochloride
• 英文别名: (2-phenyl-1(3)H-imidazol-4-yl)-acetic acid ; hydrochloride；(2-Phenyl-1(3)H-imidazol-4-yl)-essigsaeure; Hydrochlorid；2-phenylimidazol-4-ylacetic acid hydrochloride；2-(2-phenyl-1H-imidazol-5-yl)acetic acid;hydrochloride
• CAS: 110356-17-7
• 化学式: C₁₁H₁₀N₂O₂*ClH
• 分子量: 238.674
• InChiKey: MZHFXNHPCYUDSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.13
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 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：

  4(5)-(carboxymethyl)-2-phenylimidazole hydrochloride 、 甲烷 在 盐酸 、 anhydrous phosphorus trichloride 、 磷酸 作用下， 以 氯苯 为溶剂， 生成 2-(2-Phenylimidazol-4-yl)-1-hydroxy-ethane-1,1-diphosphonic acid
  参考文献：
  名称：

  Substituted alkanediphosphonic acids and pharmaceutical use

  摘要：

  烷二膦酸，特别是具有以下公式的杂芳基烷二膦酸##STR1##其中R.sub.1是一个5-成员杂芳基基团，可能与苯或环己烯核融合，并包含作为杂原子的2到4个N原子或1个或2个N原子以及1个O或S原子，且未经取代或由较低的烷基，苯基或被较低烷基，较低烷氧基和/或卤素取代的苯基取代，或由较低烷氧基，羟基，二较低烷基氨基，较低烷硫基和/或卤素取代，并/或在能够被较低烷基，较低烷氧基和/或卤素取代的N原子处于N取代状态，R.sub.2是氢，羟基，氨基，较低烷硫基或卤素，以及它们的盐，在钙代谢上具有调节作用，并可用作治疗与钙代谢障碍相关疾病的药物。例如，通过将具有以下公式的化合物转化而得到##STR2##其中X.sub.1是功能修饰磷酸基团，X.sub.2是自由或功能修饰磷酸基团，将X.sub.1和如适当的X.sub.2转化为自由磷酸基团。

  公开号：

  US04939130A1
• 作为产物：
  描述：

  4-羟基甲基-2-苯基-1H-咪唑 在 氯化亚砜 、 氢溴酸 作用下， 以 二甲基亚砜 为溶剂， 反应 32.0h， 生成 4(5)-(carboxymethyl)-2-phenylimidazole 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

文献信息

• US4939130A
  申请人：——

  公开号：US4939130A

  公开（公告）日：1990-07-03
• Substituted alkanediphosphonic acids and pharmaceutical use
  申请人：Ciba-Geigy Corporation

  公开号：US04939130A1

  公开（公告）日：1990-07-03

  Alkanediphosphonic acids, in particular heteroarylalkanediphosphonic acids of formula ##STR1## wherein R.sub.1 is a 5-membered heteroaryl radical which may be fused with benzene or cyclohexene nuclei and which contains, as hetero atoms, 2 to 4 N-atoms or 1 or 2 N-atoms as well as 1 O- or S-atom, and which is unsubstituted or C-substituted by lower alkyl, phenyl or phenyl which is substituted by lower alkyl, lower alkoxy and/or halogen, or by lower alkoxy, hydroxy, di-lower alkylamino, lower alkylthio and/or halogen, and/or is N-substituted at a N-atom which is capable of substitution by lower alkyl, lower alkoxy and/or halogen, and R.sub.2 is hydrogen, hydroxy, amino, lower alkylthio or halogen, and salts thereof, have regulatory action on calcium metabolism and can be used as medicaments for the treatment of diseases associated with impairment of calcium metabolism. The compounds are obtained for example by converting, in a compound of formula ##STR2## wherein X.sub.1 is a functionally modified phosphono group and X.sub.2 is a free or functionally modified phosphono group, X.sub.1 and, if appropriate X.sub.2, into the free phosphono group.

  烷二膦酸，特别是具有以下公式的杂芳基烷二膦酸##STR1##其中R.sub.1是一个5-成员杂芳基基团，可能与苯或环己烯核融合，并包含作为杂原子的2到4个N原子或1个或2个N原子以及1个O或S原子，且未经取代或由较低的烷基，苯基或被较低烷基，较低烷氧基和/或卤素取代的苯基取代，或由较低烷氧基，羟基，二较低烷基氨基，较低烷硫基和/或卤素取代，并/或在能够被较低烷基，较低烷氧基和/或卤素取代的N原子处于N取代状态，R.sub.2是氢，羟基，氨基，较低烷硫基或卤素，以及它们的盐，在钙代谢上具有调节作用，并可用作治疗与钙代谢障碍相关疾病的药物。例如，通过将具有以下公式的化合物转化而得到##STR2##其中X.sub.1是功能修饰磷酸基团，X.sub.2是自由或功能修饰磷酸基团，将X.sub.1和如适当的X.sub.2转化为自由磷酸基团。
• 5-Substituted Imidazole-4-acetic Acid Analogues:  Synthesis, Modeling, and Pharmacological Characterization of a Series of Novel γ-Aminobutyric Acid_C Receptor Agonists
  作者：Christian Madsen、Anders A. Jensen、Tommy Liljefors、Uffe Kristiansen、Birgitte Nielsen、Camilla P. Hansen、Mogens Larsen、Bjarke Ebert、Benny Bang-Andersen、Povl Krogsgaard-Larsen、Bente Frølund

  DOI：10.1021/jm070447j

  日期：2007.8.1

  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.