LASSBio-294 | 314021-07-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: LASSBio-294
• 英文别名: 3,4-methylenedioxybenzoyl-2-thienylhydrazone；N'-[(thiophen-2-yl)methylidene]-2H-1,3-benzodioxole-5-carbohydrazide；N-(thiophen-2-ylmethylideneamino)-1,3-benzodioxole-5-carboxamide
• CAS: 314021-07-3
• 化学式: C₁₃H₁₀N₂O₃S
• mdl: MFCD01425224
• 分子量: 274.3
• InChiKey: YMOJHAPRGAZUPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  LASSBio-294 在 Beauveria bassiana ATCC 7159 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以6%的产率得到
  参考文献：
  名称：

  Structure-based prediction and biosynthesis of the major mammalian metabolite of the cardioactive prototype LASSBio-294

  摘要：

  A new bioactive compound of the N-acylhydrazone class, LASSBio-294, was shown to produce a cardioinotropic effect and vasodilation. In this study, we report the structure-based drug metabolism prediction, biosynthesis and identification of the major mammalian metabolite of LASSBio-294. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.073
• 作为产物：
  描述：

  2-噻吩甲醛 、 3,4-亚甲基二氧苄肼 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以85%的产率得到LASSBio-294
  参考文献：
  名称：

  Thienylhydrazon with digitalis-like properties (positive inotropic effects)

  摘要：

  该发明揭示了一种具有以下式（I）的化合物，其中R1选自氢、1至6个碳原子的烷基、未取代苯基和取代苯基的群；R2选自H、烯烃、未取代酚和取代苯基的群；以及其药学上可接受的盐，具有类似毛地黄的特性。该发明进一步揭示了一种合成3,4-亚甲二氧基苯甲酰-2-硫代肼（LASSBio-294）的新方法。LASSBio-294对心脏和骨骼肌产生正性肌力作用。该发明可用于治疗充血性心力衰竭和肌肉疲劳。它不具有毛地黄苷类药物中所见的毒性效应。

  公开号：

  US07091238B1

文献信息

• CYP1A2-mediated biotransformation of cardioactive 2-thienylidene-3,4-methylenedioxybenzoylhydrazine (LASSBio-294) by rat liver microsomes and human recombinant CYP enzymes
  作者：Aline Guerra M. Fraga、Leandro Louback da Silva、Carlos Alberto Manssour Fraga、Eliezer J. Barreiro

  DOI：10.1016/j.ejmech.2010.11.024

  日期：2011.1

  We describe herein the metabolic fate of cardioactive 1,3-benzodioxolyl N-acylhydrazone prototype LASSBio-294 (4) and the structural identification of its major phase I metabolite from rat liver microsomal assays. Our results confirmed the hard-metabolic character of N-acylhydrazone (NAH) framework of LASSBio-294 (4). The development of a reproducible analytical methodology for the major metabolite by using HPLC-MS and the comparison with an authentic synthetic sample, allowed us to identify 2-thienylidene 3,4-dihydroxybenzoylhydrazine derivative (7), formed by oxidative scission of methylenedioxy bridge of LASSBio-294, as the main metabolite formed by action of CYP1A2 isoform. The identification of this isoform in the LASSBio-294 in the clearance of LASSBio-294 (4) oxidation was performed by the use of selective CYP inhibitors or human recombinant CYP enzymes. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Thienylhydrazon with digitalis-like properties (positive inotropic effects)
  申请人：University of Maryland

  公开号：US07091238B1

  公开（公告）日：2006-08-15

  The invention discloses a compound having the formula (I) wherein R1 is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, unsubstituted phenyl, and substituted phenyl; R2 is selected from the group consisting of H, alkene, un-substituted phenol, and substituted phenyl; and pharmaceutically acceptable salts thereof, having digitalis-like properties. The invention further discloses a novel method to synthesize 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294). LASSBio-294 produces positive inotropic effect on cardiac and skeletal muscle. The invention is useful for the treatment of congestive heart failure and muscle fatigue. It lacks toxic effects seen in digitalis glycosides.

  该发明揭示了一种具有以下式（I）的化合物，其中R1选自氢、1至6个碳原子的烷基、未取代苯基和取代苯基的群；R2选自H、烯烃、未取代酚和取代苯基的群；以及其药学上可接受的盐，具有类似毛地黄的特性。该发明进一步揭示了一种合成3,4-亚甲二氧基苯甲酰-2-硫代肼（LASSBio-294）的新方法。LASSBio-294对心脏和骨骼肌产生正性肌力作用。该发明可用于治疗充血性心力衰竭和肌肉疲劳。它不具有毛地黄苷类药物中所见的毒性效应。
• Structure-based prediction and biosynthesis of the major mammalian metabolite of the cardioactive prototype LASSBio-294
  作者：Emmanuel O. Carneiro、Carolina H. Andrade、Rodolpho C. Braga、Andréa C.B. Tôrres、Rosângela O. Alves、Luciano M. Lião、Carlos A.M. Fraga、Eliezer J. Barreiro、Valéria de Oliveira

  DOI：10.1016/j.bmcl.2010.04.073

  日期：2010.6

  A new bioactive compound of the N-acylhydrazone class, LASSBio-294, was shown to produce a cardioinotropic effect and vasodilation. In this study, we report the structure-based drug metabolism prediction, biosynthesis and identification of the major mammalian metabolite of LASSBio-294. (C) 2010 Elsevier Ltd. All rights reserved.