1,2-benzenedicarboxylic acid, mono[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]ester | 126613-32-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,2-benzenedicarboxylic acid, mono[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]ester
• 英文别名: 1-[2-(2-Methyl-5-nitro-1H-imidazol-1-yl)ethyl] 1,2-benzenedicarboxylate；2-[2-(2-methyl-5-nitroimidazol-1-yl)ethoxycarbonyl]benzoic acid
• CAS: 126613-32-9
• 化学式: C₁₄H₁₃N₃O₆
• 分子量: 319.274
• InChiKey: YFDJEILXTCHWQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5,7-二碘-8-羟基喹啉 、 1,2-benzenedicarboxylic acid, mono[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]ester 在 氯甲酸乙酯 、 三乙胺 作用下， 生成 1-(5,7-diiodoquinolin-8-yl)-4-[2-(2-methyl-5-nitro-1H-imidazolyl)ethyl]phthalate
  参考文献：
  名称：

  Aboul-Fadl, Tarek; Mahfouz, Nadia M., Scientia Pharmaceutica, 1998, vol. 66, # 4, p. 309 - 324

  摘要：

  DOI：
• 作为产物：
  描述：

  苯酐 、 甲硝唑 在 4-二甲氨基吡啶 作用下， 以 乙腈 为溶剂， 以87.1%的产率得到1,2-benzenedicarboxylic acid, mono[2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl]ester
  参考文献：
  名称：

  [EN] PROTEIN BINDING COMPOUNDS
  [FR] COMPOSES DE FIXATION DES PROTEINES

  摘要：

  公开号：

  WO2005025552A3

文献信息

• Protein Binding Compounds
  申请人：Klaveness Jo

  公开号：US20070259889A1

  公开（公告）日：2007-11-08

  The present invention provides a prodrug compound comprising a therapeutically effective moiety coupled via a metabolically cleavable bond to a blood protein binding moiety.

  本发明提供了一种前药化合物，其包括通过代谢可被切断的键与血液蛋白结合基团耦合的治疗有效基团。
• Compounds
  申请人：Klaveness Jo

  公开号：US20080103110A1

  公开（公告）日：2008-05-01

  The invention provides a water-soluble prodrug compound comprising a therapeutically effective moiety coupled via a metabolically cleavable bond to a protein binding moiety, wherein said therapeutically effective moiety has an anticancer, antiinflammatory, antiinfective or antipain effect, said protein binding moiety binds non-covalently to blood proteins, and the protein binding of said compound is at least 100% higher than that of the therapeutically effective moiety itself, with the exclusion of (i) the monoester of gemcitabine with azelaic acid, (ii) the monoester of dideoxycytidine with 1,12-dodecanedicarboxylic acid, (iii) 2-amino-1,9-dihydro-9(2′-(1-(10-acetyl-decanoyloxy)ethoxymethyl))-guanine, (iv) 5′-cytarabine monoester with 1,4-phenylene diacetic acid, (v) the monoester of metronidazole with 1,4-butanedicarboxylic acid, and (vi) the monoester of metronidazole with 1,6-phenylene diacetic acid; and pre-prodrugs metabolizable thereto.

  本发明提供了一种水溶性前药化合物，其包括通过代谢可裂解键与蛋白结合基团耦合的治疗有效基团，其中所述治疗有效基团具有抗癌、抗炎、抗感染或抗疼痛作用，所述蛋白结合基团与血液蛋白非共价结合，且所述化合物的蛋白结合至少比治疗有效基团本身高100％，不包括（i）阿齐拉酸与吉西他滨的单酯，（ii）1,12-十二烷二羧酸与二脱氧胞苷的单酯，（iii）2-氨基-1,9-二氢-9（2′-（1-（10-乙酰基癸酰氧）乙氧甲基）-鸟嘌呤，（iv）1,4-苯二乙酸单酯的5′-胞嘧啶，（v）1,4-丁二酸单酯的甲硝唑，以及（vi）1,6-苯二乙酸单酯的甲硝唑；以及可代谢为前药的前前药。
• [EN] DRUG CONJUGATES OF LONG CHAIN FATTY ACID OR ESTER MOIETIES AS PROTEIN BINDING PRODRUGS<br/>[FR] COMPOSÉS
  申请人：DRUG DISCOVERY LAB AS

  公开号：WO2006030217A3

  公开（公告）日：2007-03-22
• Metronidazole twin ester prodrugs: synthesis, physicochemical properties, hydrolysis kinetics and antigiardial activity
  作者：Nadia M. Mahfouz、Tarek Aboul-Fadl、Ahmed K. Diab

  DOI：10.1016/s0223-5234(98)80026-3

  日期：1998.9

  A series of identical twin esters 3a-e of metronidazole was synthesized and evaluated as potential prodrugs with improved physicochemical and pharmacokinetic properties. The synthesis of the twin esters 3a-e was achieved by interaction of metronidazole with the respective dicarboxylic acid anhydride or their dichloride. Their structures were verified by elemental and spectroscopic analyses. The lipophilicity of metronidazole and the prodrugs 3a-e, expressed as R-m values, were determined using reversed-phase TLC and revealed enhanced lipophilic properties compared with metronidazole. Reversion kinetics of the parent drug from its twin esters was investigated in aqueous buffer solutions (pH 1.2 and 7.4) as well as in biological media (80% human plasma and 20 % rat liver homogenate) at 37 degrees C using HPLC. in all cases, the hydrolysis followed pseudo-first-order kinetics in a two-step reaction (k(1) and k(2)) via the intermediate formation of the respective metronidazole hemiester. All the synthesized twin ester prodrugs 3a-e were proved to be chemically stable at acidic pH (t(1/2) similar to 25-72 h) and also at the physiological pH (t(1/2) similar to 13-40 h). Meanwhile, the release of the first molecule of metronidazole from its twin esters 3a-d ensued rapidly in 80% human plasma (t(1/2) similar to 10-150 min) and in rat liver homogenate (t(1/2) similar to 4-55 min). The resulting hemiesters 2a-d showed a sustained release of the second molecule in the same biological fluids (t(1/2) similar to 3-9 h and 1-11 h respectively). in vivo evaluation studies of metronidazole and its twin esters 3a-d in mice and 3b in rabbits revealed that the prodrugs have been absorbed almost unhydrolyzed with considerable higher plasma level. Antiparasitic activity of the synthesized compounds was evaluated in mice against Giardia muris, the prodrug 3b showed improved antigiardial activity compared to the parent drug. These results suggest that the synthesized identical twin esters 3a-d may be useful as a promising new prodrug form of metronidazole for oral drug delivery. (C) Elsevier, Paris.
• [EN] PROTEIN BINDING COMPOUNDS<br/>[FR] COMPOSES DE FIXATION DES PROTEINES
  申请人：DRUG DISCOVERY LAB AS

  公开号：WO2005025552A3

  公开（公告）日：2005-10-13