1H,3'H-2,4'-联咪唑-5-甲醛 | 279251-06-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1H,3'H-2,4'-联咪唑-5-甲醛
• 英文名称: 2-(4-1H-imidazolyl)-1H-4-imidazolcarbaldehyde
• 英文别名: 1H,1'H-[2,4']-biimidazolyl-4-carbaldehyde；1H,1'H-[2,4']biimidazolyl-4-carbaldehyde；1H,1'H-[2,4'-Biimidazole]-4-carbaldehyde；2-(1H-imidazol-5-yl)-1H-imidazole-5-carbaldehyde
• CAS: 279251-06-8
• 化学式: C₇H₆N₄O
• 分子量: 162.151
• InChiKey: ZCWOUYHXVKLQOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-叔丁基羟胺盐酸盐 、 1H,3'H-2,4'-联咪唑-5-甲醛 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以27%的产率得到(Z)-α-[2-(1H-Imidazol-4-yl)-1H-imidazol-4-yl]-N-tert-butylnitrone
  参考文献：
  名称：

  Synthesis, Structure, and Neuroprotective Properties of Novel Imidazolyl Nitrones

  摘要：

  A new series of imidazolyl nitrones spin traps has been synthesized and evaluated pharmacologically. The salient structural feature of these molecules is the presence of an imidazole moiety substituted by aromatic or heteroaromatic cycles. This connectivity imparts to the nitrone superior neuroprotective properties in vivo and in parallel reduced side effects and toxicity. Thus compound 6a (a 2-phenylimidazolyl nitrone) administered intraperitoneally protects (80%) mice from lethality induced by an intracerebroventricular administration of tert-butyl hydroperoxide (t-BHP) an oxidant capable of inducing neurodegenerative processes. Administration of the archetypal nitrone phenyl-tert-butyl nitrone (PBN) at an equimolar dose also affords some protection (60%) in this test. However, this activity is accompanied by hypothermia, whereas no such effect is apparent for 6a. Moreover, previously prepared nonsubstituted or alkyl-substituted imidazolyl nitrones were shown to be extremely toxic to rats in contrast to the compounds prepared in this study. The observed activities in vivo correlate well with the calculated partition coefficients (ClogP) and HOMO energy level.

  DOI：

  10.1021/jm991154w
• 作为产物：
  描述：

  4-cyano-2,4'-bi-1H-imidazole 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以41%的产率得到1H,3'H-2,4'-联咪唑-5-甲醛
  参考文献：
  名称：

  Synthesis, Structure, and Neuroprotective Properties of Novel Imidazolyl Nitrones

  摘要：

  A new series of imidazolyl nitrones spin traps has been synthesized and evaluated pharmacologically. The salient structural feature of these molecules is the presence of an imidazole moiety substituted by aromatic or heteroaromatic cycles. This connectivity imparts to the nitrone superior neuroprotective properties in vivo and in parallel reduced side effects and toxicity. Thus compound 6a (a 2-phenylimidazolyl nitrone) administered intraperitoneally protects (80%) mice from lethality induced by an intracerebroventricular administration of tert-butyl hydroperoxide (t-BHP) an oxidant capable of inducing neurodegenerative processes. Administration of the archetypal nitrone phenyl-tert-butyl nitrone (PBN) at an equimolar dose also affords some protection (60%) in this test. However, this activity is accompanied by hypothermia, whereas no such effect is apparent for 6a. Moreover, previously prepared nonsubstituted or alkyl-substituted imidazolyl nitrones were shown to be extremely toxic to rats in contrast to the compounds prepared in this study. The observed activities in vivo correlate well with the calculated partition coefficients (ClogP) and HOMO energy level.

  DOI：

  10.1021/jm991154w

文献信息

• Process for preparing 6-alkylidene penem derivatives
  申请人：Wyeth

  公开号：US20040132708A1

  公开（公告）日：2004-07-08

  The present invention provides a process of making compounds of formula I, which are useful for the treatment of bacterial infection or disease. 1

  本发明提供了一种制备式I化合物的方法，该化合物对治疗细菌感染或疾病有用。
• [EN] PROCESS FOR PREPARING 6-ALKYLIDENE PENEM DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE DERIVES DE 6-ALKYLIDENE PENEM
  申请人：WYETH CORP

  公开号：WO2003093277A1

  公开（公告）日：2003-11-13

  The present invention provides a process of making compounds of Formula (I), which are useful for the treatment of bacterial infection or disease.

  本发明提供了一种制备化合物的方法，该化合物符合式（I），对于治疗细菌感染或疾病非常有用。
• Novel imidazole substituted 6-methylidene-penems as broad-spectrum β-lactamase inhibitors
  作者：Aranapakam M. Venkatesan、Atul Agarwal、Takao Abe、Hideki Ushirogochi、Itsuki Yamamura、Toshio Kumagai、Peter J. Petersen、William J. Weiss、Eileen Lenoy、Youjun Yang、David M. Shlaes、John L. Ryan、Tarek S. Mansour

  DOI：10.1016/j.bmc.2004.08.039

  日期：2004.11

  several beta-lactamase inhibitors such as clavulanic acid, sulbactam, and tazobactam are widely used in the clinic in combination with beta-lactam antibiotics. However, single point mutations within these enzymes have allowed bacteria to overcome the inhibitory effect of the commercially approved beta-lactamase inhibitors. Although the commercially available beta-lactamase inhibitor/beta-lactam antibiotic

  β-内酰胺酶是细菌产生的丝氨酸和金属依赖性酶，可防御β-内酰胺抗生素。细菌产生的A类，B类和C类酶使得在某些情况下使用β-内酰胺类抗生素无效。为了克服对β-内酰胺抗生素的抗药性，几种β-内酰胺酶抑制剂（例如克拉维酸，舒巴坦和他唑巴坦）与β-内酰胺抗生素联合用于临床。但是，这些酶中的单点突变使细菌克服了商业认可的β-内酰胺酶抑制剂的抑制作用。尽管市售的β-内酰胺酶抑制剂/β-内酰胺类抗生素组合物对产生A类细菌和许多扩展谱的β-内酰胺酶（ESBL' s）产生细菌，它们对表达C类酶的细菌效果较差。为了避免这个问题，基于模型研究，合成了几种新型咪唑取代的6-亚甲基-青霉烯衍生物，并针对产生各种β-内酰胺酶的分离物进行了测试。本文研究了这些化合物的合成和构效关系（SAR）。
• PROCESS FOR PREPARING 6-ALKYLIDENE PENEM DERIVATIVES
  申请人：Wyeth

  公开号：EP1499620A1

  公开（公告）日：2005-01-26
• Synthesis, Structure, and Neuroprotective Properties of Novel Imidazolyl Nitrones
  作者：Alain Dhainaut、André Tizot、Eric Raimbaud、Brian Lockhart、Pierre Lestage、Solo Goldstein

  DOI：10.1021/jm991154w

  日期：2000.6.1

  A new series of imidazolyl nitrones spin traps has been synthesized and evaluated pharmacologically. The salient structural feature of these molecules is the presence of an imidazole moiety substituted by aromatic or heteroaromatic cycles. This connectivity imparts to the nitrone superior neuroprotective properties in vivo and in parallel reduced side effects and toxicity. Thus compound 6a (a 2-phenylimidazolyl nitrone) administered intraperitoneally protects (80%) mice from lethality induced by an intracerebroventricular administration of tert-butyl hydroperoxide (t-BHP) an oxidant capable of inducing neurodegenerative processes. Administration of the archetypal nitrone phenyl-tert-butyl nitrone (PBN) at an equimolar dose also affords some protection (60%) in this test. However, this activity is accompanied by hypothermia, whereas no such effect is apparent for 6a. Moreover, previously prepared nonsubstituted or alkyl-substituted imidazolyl nitrones were shown to be extremely toxic to rats in contrast to the compounds prepared in this study. The observed activities in vivo correlate well with the calculated partition coefficients (ClogP) and HOMO energy level.