8-bromo-1,2,3,5-tetrahydro-4H-pyrido[2,3-b][1,4]diazepin-4-one | 941604-90-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 8-bromo-1,2,3,5-tetrahydro-4H-pyrido[2,3-b][1,4]diazepin-4-one
• 英文别名: 8-bromo-2,3-dihydro-1H-pyrido[2,3-b][1,4]diazepin-4(5H)-one；8-bromo-1,2,3,5-tetrahydropyrido[2,3-b][1,4]diazepin-4-one
• CAS: 941604-90-6
• 化学式: C₈H₈BrN₃O
• 分子量: 242.075
• InChiKey: FOOYKUCJIQWSSY-UHFFFAOYSA-N

物化性质

• 沸点：
  340.5±52.0 °C(Predicted)
• 密度：
  1.88±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-bromo-1,2,3,5-tetrahydro-4H-pyrido[2,3-b][1,4]diazepin-4-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 8-bromo-2,3,4,5-tetrahydro-1H-pyrido[2,3-b][1,4]diazepine
  参考文献：
  名称：

  2,3,4,5-Tetrahydro-1H-pyrido[2,3-b and e][1,4]diazepines as inhibitors of the bacterial enoyl ACP reductase, FabI

  摘要：

  In the search for new antibacterial agents, the enzyme FabI has been identified as an attractive target. Employing a structure guided approach, the previously reported ene-amide series of FabI inhibitors were expanded to include 2,3,4,5-tetrahydro-1H-pyrido[2,3-b and e][1,4]diazepines. These novel series incorporate additional H-bonding functions and can be more water soluble than their naphthyridinone progenitors; diazepine 16c is shown to be efficacious in a mouse infection model. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.094
• 作为产物：
  描述：

  1-(2-amino-5-bromopyridin-3-yl)azetidin-2-one 在 titanium(IV) isopropylate 甲醇 、 二氯甲烷 、 silica gel 作用下， 以 甲苯 、 hexanes 为溶剂， 反应 31.0h， 生成 8-bromo-1,2,3,5-tetrahydro-4H-pyrido[2,3-b][1,4]diazepin-4-one
  参考文献：
  名称：

  3-Heterocyclylacrylamide Compounds as Fab I Inhibitors and Antibacterial Agents

  摘要：

  本发明的部分涉及具有FabI抑制性质的化合物。这些化合物也可能抑制其他酶，包括那些在结构或功能上类似于FabI的酶，例如Fab K。还提供了包括所述化合物的试剂盒和组合物。还揭示了治疗细菌性疾病患者的方法。

  公开号：

  US20090156578A1

文献信息

• [EN] SUBSTITUTED PYRIDINE DERIVATIVES AS FABI INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDINE SUBSTITUÉS EN TANT QU'INHIBITEURS DE FABI
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2013080222A1

  公开（公告）日：2013-06-06

  The present invention provides substituted pyridine derivatives of formula (I), which may be therapeutically useful as as anti-bacterial agents, more particulalrly FabI inhibitors. Formula(I) in which R1 to R5 and L have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage anti-bacterial agents, more particularly FabI inhibitors. The present invention also provides methods for synthesizing and administering the FabI inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the FabI inhibitor compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

  本发明提供了式(I)的取代吡啶衍生物，其可能作为抗细菌剂，特别是FabI抑制剂，具有治疗用途。式(I)中，R1至R5和L具有说明书中给出的含义，以及用于治疗和预防疾病或失调的药用可接受盐，特别是在有优势使用抗细菌剂，尤其是FabI抑制剂的疾病或失调中的用途。本发明还提供了合成和管理FabI抑制剂化合物的方法。本发明还提供了包含至少一种FabI抑制剂化合物和用于其的药用可接受载体、稀释剂或助剂的药物制剂。
• SUBSTITUTED PYRIDINE DERIVATIVES AS FABI INHIBITORS
  申请人：Aurigene Discovery Technologies Limited

  公开号：US20140336153A1

  公开（公告）日：2014-11-13

  The present invention provides substituted pyridine derivatives of formula (I), which may be therapeutically useful as as anti-bacterial agents, more particularly FabI inhibitors. Formula (I) in which R1 to R5 and L have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage anti-bacterial agents, more particularly FabI inhibitors. The present invention also provides methods for synthesizing and administering the FabI inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the FabI inhibitor compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor.

  本发明提供了式（I）的取代吡啶衍生物，其可作为抗菌剂，更特别地是FabI抑制剂，具有治疗上的用途。式（I）中，R1至R5和L具有规范中所给出的含义，以及其药学上可接受的盐，在特定的疾病或疾病预防治疗中有用，特别是在有优势的抗菌剂，更特别地是FabI抑制剂的疾病或疾病预防治疗中的使用。本发明还提供了合成和给予FabI抑制剂化合物的方法。本发明还提供了包含至少一种FabI抑制剂化合物的药物配方，以及与其药学上可接受的载体、稀释剂或赋形剂一起使用的药物配方。
• 3-Heterocyclylacrylamide Compounds as Fab I Inhibitors and Antibacterial Agents
  申请人：Pauls Henry

  公开号：US20090156578A1

  公开（公告）日：2009-06-18

  In part, the present invention is directed towards compounds with FabI inhibiting properties. Such compounds may also inhibit other enzymes, including those similar to FabI either structurally or functionally, for example, Fab K. Kits and compositions that include the disclosed compounds are also provided. Methods of treating a subject with a bacterial illness is also disclosed.

  本发明的部分涉及具有FabI抑制性质的化合物。这些化合物也可能抑制其他酶，包括那些在结构或功能上类似于FabI的酶，例如Fab K。还提供了包括所述化合物的试剂盒和组合物。还揭示了治疗细菌性疾病患者的方法。
• WO2007/67416
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors
  作者：Mohamed Takhi、Kandepu Sreenivas、Chandrashekar K. Reddy、Mahadari Munikumar、Kolakota Praveena、Pabolu Sudheer、Bandaru N.V.M. Rao、Gollamudi Ramakanth、Jampala Sivaranjani、Shardaprasad Mulik、Yeruva R. Reddy、Krishnamurthy Narasimha Rao、Rentala Pallavi、Anirudha Lakshminarasimhan、Sunil K. Panigrahi、Thomas Antony、Iskandar Abdullah、Yean K. Lee、Murali Ramachandra、Rohana Yusof、Noorsaadah A. Rahman、Hosahalli Subramanya

  DOI：10.1016/j.ejmech.2014.07.036

  日期：2014.9

  A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.