1-(3-dodecyloxyphenyl)-5-[2-(ethyloxy)-2-oxoethyl]-1-hydroxy-3-oxo-1,2-dihydropyrrolo[3,4-c]pyridinium bromide | 1179810-96-8

• 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: 1-(3-dodecyloxyphenyl)-5-[2-(ethyloxy)-2-oxoethyl]-1-hydroxy-3-oxo-1,2-dihydropyrrolo[3,4-c]pyridinium bromide
• 英文别名: 1-[3-(dodecyloxy)phenyl]-5-(2-ethoxy-2-oxoethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-5-ium bromide；ethyl 2-[1-(3-dodecoxyphenyl)-1-hydroxy-3-oxo-2H-pyrrolo[3,4-c]pyridin-5-ium-5-yl]acetate;bromide
• CAS: 1179810-96-8
• 化学式: Br*C₂₉H₄₁N₂O₅
• 分子量: 577.559
• InChiKey: WKPHGRMCMRHTBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.78
• 重原子数：
  37
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  88.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3-dodecyloxyphenyl)-5-[2-(ethyloxy)-2-oxoethyl]-1-hydroxy-3-oxo-1,2-dihydropyrrolo[3,4-c]pyridinium bromide 在 三乙酰氧基硼氢化钠 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 0.17h， 以51%的产率得到ethyl 3-aminocarbonyl-[4-(3-dodecyloxybenzoyl)-1,4-dihydropyridin-1-yl]acetate
  参考文献：
  名称：

  Development of isoniazid–NAD truncated adducts embedding a lipophilic fragment as potential bi-substrate InhA inhibitors and antimycobacterial agents

  摘要：

  Isoniazid-NAD truncated adducts embedding a lipophilic fragment were designed, synthesized and evaluated as inhibitors of the enoyl-acyl carrier protein (ACP) reductase (InhA) of Mycobacterium tuberculosis and as antimycobacterial agents. These compounds, planned as bi-substrate inhibitors and inspired from the active metabolite of isoniazid, combine both the nicotinamide moiety of the cofactor NAD and a lipophilic hydrocarbon chain mimic of the InhA substrate. The lipophilic fragment was introduced using either Suzuki-Miyaura cross-coupling or a classical nucleophilic substitution reaction. Several compounds developed in this work were indeed able to inhibit the InhA activity and showed promising antimycobacterial activities. However a direct correlation between the expressed activity and the bi-substrate mode of action could not yet be unambiguously demonstrated (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.016
• 作为产物：
  描述：

  1-(3-dodecyloxyphenyl)-1-hydroxy-1,2-dihydropyrrolo[3,4-c]pyridine-3-one 、 溴乙酸乙酯 以 四氢呋喃 为溶剂， 以54%的产率得到1-(3-dodecyloxyphenyl)-5-[2-(ethyloxy)-2-oxoethyl]-1-hydroxy-3-oxo-1,2-dihydropyrrolo[3,4-c]pyridinium bromide
  参考文献：
  名称：

  Development of isoniazid–NAD truncated adducts embedding a lipophilic fragment as potential bi-substrate InhA inhibitors and antimycobacterial agents

  摘要：

  Isoniazid-NAD truncated adducts embedding a lipophilic fragment were designed, synthesized and evaluated as inhibitors of the enoyl-acyl carrier protein (ACP) reductase (InhA) of Mycobacterium tuberculosis and as antimycobacterial agents. These compounds, planned as bi-substrate inhibitors and inspired from the active metabolite of isoniazid, combine both the nicotinamide moiety of the cofactor NAD and a lipophilic hydrocarbon chain mimic of the InhA substrate. The lipophilic fragment was introduced using either Suzuki-Miyaura cross-coupling or a classical nucleophilic substitution reaction. Several compounds developed in this work were indeed able to inhibit the InhA activity and showed promising antimycobacterial activities. However a direct correlation between the expressed activity and the bi-substrate mode of action could not yet be unambiguously demonstrated (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.016

文献信息

• NOVEL ANTI-INFECTIOUS DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND USES OF SAID DERIVATIVES IN TREATMENT
  申请人：Bernadou Jean

  公开号：US20110092536A1

  公开（公告）日：2011-04-21

  The invention relates to bi-substrate inhibitor molecules associating (i) a pyridine, pyridinium or dihydropyridine-type structure allied to active metabolites of isoniazide, or related structures, and (ii) a hydrophobic substituent. The invention also relates to the method for producing said molecules, to the pharmaceutical compositions containing said molecules, and to the use thereof as inhibitors of enoyl reductase for the preparation of a medicament, especially an anti-infectious medicament for the treatment of tuberculosis.

  该发明涉及与异烟肼的活性代谢产物相关的吡啶、吡啶盐或二氢吡啶类型结构以及疏水取代基相结合的双底物抑制分子。该发明还涉及制备该分子的方法、含有该分子的药物组合物，以及将其用作烯醇还原酶抑制剂的用途，用于制备药物，特别是用于治疗结核病的抗感染药物。
• NOUVEAUX DÉRIVÉS ANTI-INFECTIEUX, LEUR PROCÉDÉ DE PRÉPARATION, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT ET LEURS UTILISATIONS EN THÉRAPEUTIQUE
  申请人：Centre National de la Recherche Scientifique (CNRS)

  公开号：EP2240449B1

  公开（公告）日：2016-01-06
• US8710073B2
  申请人：——

  公开号：US8710073B2

  公开（公告）日：2014-04-29
• Development of isoniazid–NAD truncated adducts embedding a lipophilic fragment as potential bi-substrate InhA inhibitors and antimycobacterial agents
  作者：Tamara Delaine、Vania Bernardes-Génisson、Annaïk Quémard、Patricia Constant、Bernard Meunier、Jean Bernadou

  DOI：10.1016/j.ejmech.2010.07.016

  日期：2010.10

  Isoniazid-NAD truncated adducts embedding a lipophilic fragment were designed, synthesized and evaluated as inhibitors of the enoyl-acyl carrier protein (ACP) reductase (InhA) of Mycobacterium tuberculosis and as antimycobacterial agents. These compounds, planned as bi-substrate inhibitors and inspired from the active metabolite of isoniazid, combine both the nicotinamide moiety of the cofactor NAD and a lipophilic hydrocarbon chain mimic of the InhA substrate. The lipophilic fragment was introduced using either Suzuki-Miyaura cross-coupling or a classical nucleophilic substitution reaction. Several compounds developed in this work were indeed able to inhibit the InhA activity and showed promising antimycobacterial activities. However a direct correlation between the expressed activity and the bi-substrate mode of action could not yet be unambiguously demonstrated (C) 2010 Elsevier Masson SAS. All rights reserved.