7-甲基-5,6,7,8-四氢咪唑并[1,2-a]吡嗪-2-甲醛 | 623564-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 7-甲基-5,6,7,8-四氢咪唑并[1,2-a]吡嗪-2-甲醛
• 英文名称: 7-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carbaldehyde
• 英文别名: 7-methyl-6,8-dihydro-5H-imidazo[1,2-a]pyrazine-2-carbaldehyde
• CAS: 623564-20-5
• 化学式: C₈H₁₁N₃O
• 分子量: 165.195
• InChiKey: IMLXOMJBYPJJOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  7-甲基-5,6,7,8-四氢咪唑并[1,2-a]吡嗪-2-甲醛 在 phosphate buffer 、 乙醚 、 三乙胺 、 magnesium bromide 、 锌 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 25.0h， 生成 (5R),(6Z)-6-(7-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-2-ylmethylene)-7-oxo-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium salt
  参考文献：
  名称：

  Structure-Activity Relationship of 6-Methylidene Penems Bearing 6,5 Bicyclic Heterocycles as Broad-Spectrum β-Lactamase Inhibitors:  Evidence for 1,4-Thiazepine Intermediates with C7 R Stereochemistry by Computational Methods

  摘要：

  The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C beta-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C beta-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both beta-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.

  DOI：

  10.1021/jm060021p
• 作为产物：
  描述：

  咪唑并[1,2-A]吡嗪-2-甲酸乙酯 在 palladium on activated charcoal 盐酸 、 氢气 、 二异丁基氢化铝 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， -78.0~20.0 ℃ 、275.79 kPa 条件下， 反应 20.5h， 生成 7-甲基-5,6,7,8-四氢咪唑并[1,2-a]吡嗪-2-甲醛
  参考文献：
  名称：

  Structure-Activity Relationship of 6-Methylidene Penems Bearing 6,5 Bicyclic Heterocycles as Broad-Spectrum β-Lactamase Inhibitors:  Evidence for 1,4-Thiazepine Intermediates with C7 R Stereochemistry by Computational Methods

  摘要：

  The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C beta-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-1 were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C beta-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both beta-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.

  DOI：

  10.1021/jm060021p

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。
• Bicyclic 6-alkylidene-penems as class-D beta-lactamases inhibitors
  申请人：Mansour Suhayl Tarek

  公开号：US20060276445A1

  公开（公告）日：2006-12-07

  This invention relates to certain bicyclic 6-alkylidene penems which act as a inhibitor of class-D enzymes. β-Lactamases hydrolyze β-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present invention when combined with β-lactam antibiotics will provide an effective treatment against life threatening bacterial infections. In accordance with the present invention there are provided compounds of general formula I or a pharmaceutically acceptable salt or in vivo hydrolyzable ester R 5 thereof: wherein: One of A and B denotes hydrogen and the other an optionally substituted fused bicyclic heteroaryl group; and X═O or S.

  这项发明涉及某些具有双环6-烷基亚烯基青霉素结构的化合物，其作为D类酶的抑制剂。β-内酰胺酶水解β-内酰胺类抗生素，因此是细菌耐药的主要原因。本发明的化合物与β-内酰胺类抗生素结合后，将提供一种有效的治疗方法，用于治疗威胁生命的细菌感染。根据本发明，提供了一般式I的化合物，或其药学上可接受的盐或体内可水解的酯R5：其中：A和B中的一个表示氢，另一个表示可选择取代的融合双环杂环芳基团；X＝O或S。
• [EN] BICYCLIC 6-ALKYLIDENE-PENEMS AS ß-LACTAMASES INHIBITORS<br/>[FR] PENEMES 6-ALKYLIDENE BICYCLIQUES UTILISES EN TANT QU'INHIBITEURS DE ss-LACTAMASES
  申请人：WYETH CORP

  公开号：WO2003093279A1

  公开（公告）日：2003-11-13

  The present invention provides a compound of Formula (I), pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.

  本发明提供了一种化合物（I）的配方、药物组合物以及其用于治疗患有细菌感染或疾病的患者的用途。
• [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。
• Bicyclic and Tricyclic Substituted 6-Methylidene Carbapenems as Broad Spectrum Beta-Lactamase Inhibitors
  申请人：Mansour Tarek Suhayl

  公开号：US20100063023A1

  公开（公告）日：2010-03-11

  Provided is a β-lactamase antibiotic and a compound of formula I, a process of producing the compound, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.

  本文提供了一种β-内酰胺酶抗生素和一种I式化合物，以及制备该化合物的过程、制药组合物及其用于治疗患有细菌感染或疾病的患者。