(Z)-acetyloxymethoxyimino-[methyl-[2-[5-(4-methylphenyl)-1-(4-methylsulfonylphenyl)pyrazole-3-carbonyl]oxyethyl]amino]-oxidoazanium | 1046152-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (Z)-acetyloxymethoxyimino-[methyl-[2-[5-(4-methylphenyl)-1-(4-methylsulfonylphenyl)pyrazole-3-carbonyl]oxyethyl]amino]-oxidoazanium
• CAS: 1046152-10-6
• 化学式: C₂₄H₂₇N₅O₈S
• 分子量: 545.573
• InChiKey: VPCHEXSLBROUBU-WCTVFOPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  167
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  O2-acetoxymethyl-1-[N-(2-methylsulfonyloxyethyl)-N-methylamino]diazen-1-ium-1,2-diolate 、 1-(4-(methylsulfonyl)phenyl)-5-(p-tolyl)-1H-pyrazole-3-carboxylic acid 在 sodium carbonate 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 72.0h， 以28%的产率得到(Z)-acetyloxymethoxyimino-[methyl-[2-[5-(4-methylphenyl)-1-(4-methylsulfonylphenyl)pyrazole-3-carbonyl]oxyethyl]amino]-oxidoazanium
  参考文献：
  名称：

  Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids: Synthesis, nitric oxide release studies and anti-inflammatory activities

  摘要：

  A new group of hybrid nitric oxide-releasing anti-inflammatory drugs (NONO-coxibs) wherein an O(2)-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (11a-c) NO-donor moiety is attached directly to the carboxylic acid group of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids were synthesized. The diazen-1-ium-1,2-diolate compounds 11a-c all released a low amount of NO upon incubation with phosphate buffer (PBS) at pH 7.4 (7.7-9.3% range). In comparison, the percentage of NO released was significantly higher (67.5-73.6% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum. These incubation studies suggest that both NO and the anti-inflammatory 1-(4-methanesulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3- carboxylic acid (9a-c) would be released from the parent NONO-coxib upon in vivo cleavage by non-specific serum esterases. The 1-(4-methanesulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3- carboxylic acids (9a-c) exhibited AI activities (ID(50) = 85.2-104.4 mg/kg po range) between that exhibited by the reference drugs aspirin (ID(50) = 128.7 mg/kg po) and celecoxib (ID(50) = 10.8 mg/kg po). Hybrid ester anti-inflammatory/NO-donor prodrugs (NONO-coxibs) offers a potential drug design concept targeted toward the development of anti-inflammatory drugs that are devoid of adverse ulcerogenic and/or cardiovascular effects. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.028

文献信息

• [EN] NO-RELEASING NONOATE(OXYGEN-BOUND)CHROMENE CONJUGATES<br/>[FR] CONJUGUÉS DE NONOATE(LIÉ À L'OXYGÈNE)CHROMÈNE LIBÉRANT DE L'OXYDE NITRIQUE
  申请人：EUCLISES PHARMACEUTICALS INC

  公开号：WO2015109014A1

  公开（公告）日：2015-07-23

  The present invention provides NO-releasing NONOate(oxygen bound)chromene conjugates, having the structure of Formula (I): wherein Z, R1, R2, R3, R4, R5, R6, and R7 are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis, or acne, using a compound of Formula (I).

  本发明提供了释放NO的NONOate（氧结合）香豆素共轭物，其具有如下结构（I）的结构：其中Z、R1、R2、R3、R4、R5、R6和R7如详细描述中所定义；包括至少一种化合物的制药组合物（I）；以及使用化合物（I）有益于愈合伤口、预防和治疗癌症，或治疗光老化性角化症、囊性纤维化或痤疮的方法。
• NO-RELEASING NONOATE(NITROGEN-BOUND)SULFONAMIDE-LINKED-COXIB ANTI-CANCER AGENTS
  申请人：Euclises Pharmaceuticals, Inc.

  公开号：US20140018544A1

  公开（公告）日：2014-01-16

  The present invention provides NO-releasing NONOate(nitrogen bound)sulfonamide-linked-coxib anti-cancer agents, having the structure of Formula (I): wherein R 1 , X, L, R 2 , R 3 , R 4 , and Z are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis or acne, using a compound of Formula (I).

  本发明提供了一种NO释放的NONOate（氮结合）磺酰胺-联苯并咪唑类抗癌药物，具有以下结构式（I）：其中R1、X、L、R2、R3、R4和Z如详细说明中所定义；包括至少一种式（I）化合物的制药组合物；以及使用式（I）化合物有益于治疗伤口、预防和治疗癌症、或治疗光化性角化症、囊性纤维化或痤疮的方法。
• US8859781B2
  申请人：——

  公开号：US8859781B2

  公开（公告）日：2014-10-14
• [EN] NO-RELEASING NONOATE (NITROGEN-BOUND) SULFONAMIDE-LINKED-COXIB ANTI-CANCER AGENTS<br/>[FR] AGENTS ANTICANCÉREUX DE COXIB LIÉS À UN SULFONAMIDE (LIAISON À L'AZOTE) DE NONOATE À LIBÉRATION DE NO
  申请人：EUCLISES PHARMACEUTICALS INC

  公开号：WO2014012074A2

  公开（公告）日：2014-01-16

  The present invention provides NO-releasing NONOate(nitrogen bound)sulfonamide- linked-coxib anti-cancer agents, having the structure of Formula (I): wherein R1, X, L, R2, R3, R4, and Z are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis or acne, using a compound of Formula (I).
• [EN] DEUTERATED NO-RELEASING NONOATE(OXYGEN-BOUND)CHROMENE CONJUGATES<br/>[FR] CONJUGUÉS DE CHROMÈNE DÉUTÉRÉ NONOATE(OXYGÈNE-LIÉ) LIBÉRANT DU NO
  申请人：EUCLISES PHARMACEUTICALS INC

  公开号：WO2015109017A2

  公开（公告）日：2015-07-23

  The present invention provides deuterated NO-releasing NONOate(oxygen bound)chromene conjugates, having the structure of Formula (I): wherein Z, R1, R2, R3, R4, R5, R6, and R7 are as defined in the detailed description; pharmaceutical compositions comprising at least one compound of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis, or acne, using a compound of Formula (I).