7,8-dimethyl-1-((pyrrolidine-1-carbonyl)oxy)phenazine 5,10-dioxide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7,8-dimethyl-1-((pyrrolidine-1-carbonyl)oxy)phenazine 5,10-dioxide
• 英文别名: (7,8-Dimethyl-5-oxido-10-oxophenazin-10-ium-1-yl) pyrrolidine-1-carboxylate；(7,8-dimethyl-5-oxido-10-oxophenazin-10-ium-1-yl) pyrrolidine-1-carboxylate
• 化学式: C₁₉H₁₉N₃O₄
• 分子量: 353.378
• InChiKey: OXVJIQFEQGIBBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  75.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-甲氧基儿茶酚 在 三乙烯二胺 、 三溴化硼 、 四氯苯醌 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醚 、 甲苯 为溶剂， 反应 38.0h， 生成 7,8-dimethyl-1-((pyrrolidine-1-carbonyl)oxy)phenazine 5,10-dioxide
  参考文献：
  名称：

  吩嗪 5,10-二氧化物天然产物碘宁和粘菌素的新前药和类似物促进对人急性髓系白血病细胞的选择性细胞毒性

  摘要：

  需要针对急性髓系白血病（AML）治疗的新化疗策略。我们最近证明吩嗪 5,10-二氧化物天然产物碘宁 ( 3 ) 和粘菌素 ( 4 ) 对 MOLM-13 人 AML 细胞表现出有效的缺氧选择性细胞死亡，并且N-氧化物功能对于细胞毒活性。哺乳动物细胞系上专门针对吩嗪 5,10-二氧化物的构效关系研究很少，目前的工作描述了我们在天然化合物碘宁 ( 3 ) 和粘菌素 ( 4 ) 的体外先导化合物优化方面所做的努力。前药策略表明氨基甲酸酯侧链是最佳的苯酚连接基团。如果烷基或氨基甲酸酯侧链连接到苯酚的位置 1，则吩嗪骨架的第 6 位不带氧取代基（–OH 或 -OCH 3 ）的衍生物仍能保持效力。 7,8-二卤代-和 7,8与所有其他研究化合物相比，1-羟基吩嗪 5,10-二氧化物 ( 21 ) 的二甲基化类似物在 MOLM-13 细胞中显示出更高的细胞毒性效力。另一方面，二卤代化合物对成肌细胞 H9c2

  DOI：

  10.1039/d1md00020a

文献信息

• Substituted phenazines and methods of treating cancer and bacterial diseases
  申请人：Rongved Pål

  公开号：US11046678B2

  公开（公告）日：2021-06-29

  Compounds of formula (Ia) or (Ib), or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the compounds, and methods of treatment using the compounds.

  式 (Ia) 或 (Ib) 的化合物，或其药学上可接受的盐、 包含这些化合物的药物组合物，以及使用这些化合物的治疗方法。
• N-OXIDE HETEROCYCLES FOR USE IN THE TREATMENT OF CANCER AND BACTERIAL DISEASES
  申请人：Rongved, Pål

  公开号：EP3555052A1

  公开（公告）日：2019-10-23
• COMPOUNDS
  申请人：RONGVED Pål

  公开号：US20200095237A1

  公开（公告）日：2020-03-26

  The invention provides compounds of general formula (I′), and their pharmaceutically acceptable salts: wherein: Z is a group having the formula: -T-S-A-Y in which: T is a group selected from —O—, —NH—, —S—, —(XCR 7 R 8 )— (where R 7 and R 8 is independently —H or C 1-3 alkyl and X is selected from from —O—, —NH—, —S—); S is —(C═O)—, —(SO 2 )—, —(PO 2 )—; A, —O—, —NH—, —S— or —NH(CO)—, —(CR 7 R 8 X)— (where R 7 and R 8 is independently —H or C 1-3 alkyl and X is selected from from —O—, —NH—, —S—), -T-S-A- is a group susceptible to hydrolytic and/or enzymatic cleavage in vivo to leave a group selected from —OH, —NH 2 , —SH, —COOH, —CONH 2 , —O—(CR 7 R 8 )—COOH and —(CR 7 R 8 )—CONH 2 ; Y is one or more targeting groups or a lipophilic or hydrophilic group affecting the solubility in water and the biodistribution in a living organism or a living cell; R 1 -R 6 are independently selected from hydrogen, halogen (e.g. F, Cl, Br, I), lower alkyl (e.g. C 1-6 alkyl), optionally substituted with an acidic group which is —COOH, —SO 3 H, —PO 3 H 2 or —B(OH) 2 . Such compounds find particular use as anti-neoplastic and anti-infective agents.
• SUBSTITUTED PHENAZINES AND METHODS OF TREATING CANCER AND BACTERIAL DISEASES
  申请人：Rongved Pål

  公开号：US20210292313A1

  公开（公告）日：2021-09-23

  A combination product comprising a carbapenem and a compound of formula (I′), or a pharmaceutically acceptable salt thereof: a pharmaceutical composition comprising the combination product; and methods of treating bacterial or fungal infections using the combination product and pharmaceutical composition.
• [EN] N-OXIDE HETEROCYCLES FOR USE IN THE TREATMENT OF CANCER AND BACTERIAL DISEASES<br/>[FR] HÉTÉROCYCLES N-OXYDE POUR UTILISATION DANS LE TRAITEMENT DU CANCER ET DES MALADIES BACTÉRIENNES
  申请人：UNIV OSLO

  公开号：WO2018109504A1

  公开（公告）日：2018-06-21

  The invention provides compounds of general formula (P), and their pharmaceutically acceptable salts: (Formula (I')) wherein X is an N-oxide functionality (N+-0"), or CH; Z is a group susceptible to hydrolytic and/or enzymatic cleavage in vivo to form a group selected from -OH, -COOH, -CONH2, -O-Q-COOH and -0-Q-CONH2 (where Q is a straight chained or branched alkylene group, preferably Ci-3 alkylene, e.g. methylene), and Z is optionally linked to one or more targeting groups; Ri and R2 are independently selected from hydrogen, lower alkyl (e.g. C1 -6 alkyl), halogen (e.g. F, CI, Br, I), an acidic group which is -COOH, -S03H, -P03H2 or -B(OH)2; and an aryl group (e.g. phenyl); or R] and R2, together with the intervening carbon atoms, form an optionally substituted aromatic group; each W is independently selected from lower alkyl (e.g. Ci-6 alkyl), halogen (e.g. F, CI, Br, I), OH, and an acidic group which is -COOH, -S03H, -P03H2 or -B(OH)2; and p is an integer from 0 to 3. Such compounds find particular use as anti-neoplastic and anti-infective agents.