莫非佐酸 | 78967-07-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 莫非佐酸
• 中文别名: 莫苯唑酸；莫芬唑酸；莫非唑酸
• 英文名称: mofezolac
• 英文别名: 2-(3,4-bis(4-methoxyphenyl)isoxazol-5-yl)acetic acid；3,4-bis(4-methoxyphenyl)-isoxazol-5-acetic acid；2-[3,4-bis(4-methoxyphenyl)-1,2-oxazol-5-yl]acetic acid
• CAS: 78967-07-4
• 化学式: C₁₉H₁₇NO₅
• 分子量: 339.348
• InChiKey: DJEIHHYCDCTAAH-UHFFFAOYSA-N

物化性质

• 熔点：
  147.5℃
• 沸点：
  527.2±50.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  81.8
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H317,H319
• 储存条件：
  -20℃

制备方法与用途

莫非唑酸是一种非甾体抗炎药(NSAID)，是一种选择性、可逆的口服活性COX-1抑制剂，其IC50值为1.44 nM。虽然它对COX-2的抑制活性较弱（IC50值为447 nM），但莫非唑酸仍能有效缓解疼痛并具有抗炎作用[1]。

反应信息

• 作为反应物：
  描述：

  莫非佐酸 在 dimethyl sulfide borane 、 双氧水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以68%的产率得到3,4-bis(4-methoxyphenyl)-5-hydroxyethylisoxazole
  参考文献：
  名称：

  [EN] HETEROCYCLES AND THEIR RADIOLABELED ANALOGS USEFUL AS COX-1 SELECTIVE INHIBITORS
  [FR] HÉTÉROCYCLES ET LEURS ANALOGUES RADIOMARQUÉS UTILES EN TANT QU'INHIBITEURS SÉLECTIFS DE COX-1

  摘要：

  本发明涉及一种新型杂环化合物，这些化合物是环氧合酶-1（COX-1）的有效和选择性抑制剂，以及它们的放射标记衍生物，这些衍生物既可用作多种病理病变的诊疗药物。

  公开号：

  WO2014115020A1
• 作为产物：
  描述：

  [(4-甲氧苯基)次甲基]氮烷氧化 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 莫非佐酸
  参考文献：
  名称：

  Translational impact of novel widely pharmacological characterized mofezolac-derived COX-1 inhibitors combined with bortezomib on human multiple myeloma cell lines viability

  摘要：

  A set of novel diarylisoxazoles has been projected using mofezolac (1) as a lead compound to investigate structure-inhibitory activity relationships of new compounds and the cyclooxygenases (COXs) catalytic activity. Mofezolac was chosen because is the most potent and selective reversible COX-1 inhibitor [COX-1 IC50 = 0.0079 mu M and COX-2 IC50 > 50 mu M, with a selectivity index (SI) in favor of COX-1 higher than 6300]. Seventeen new compounds were synthesized in fair to good yields and evaluated for their COXs inhibitory activity and selectivity. Sls ranged between 1 and higher than 11903,4-Bis(4-methoxyphenyl)-5-vinylisoxazole (22) has the highest SI with COX-1 IC50 = 0.042 mu M and COX-2 IC50 > 50 mu M. 1 and 22 were superior to aspirin in inhibiting platelet aggregation (IC50 = 0.45, 0.63 and 1.11 mu M, respectively) in human platelet rich plasma (hPRP) assay. They did not induce blood coagulation and hemolysis, and are neither genotoxic nor mutagen. 1 and 22 slightly increase bortezomib cytotoxic effect on multiple myeloma (MM) cell lines (NCI-H929 and RPMI-8226) and affects MM cell cycle and apoptosis when co-administered with the proteasome inhibitor bortezomib, a drug clinically used to treat plasma cell neoplasms including MM. In addition, structure-based binding mode of 1 and 22, through Fingerprints for Ligands and Proteins (FLAG) calculation, allowed to explain the one order of magnitude difference between COX-1 IC50 values of the two compounds. Specifically, the higher inhibitory potency seems due to the formation of a H-bond between COX-1 S530 and the carboxyl, present in 1 and absent in 22. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.12.029

文献信息

• TROPAN COMPOUND
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1785421A1

  公开（公告）日：2007-05-16

  The conventional anticholinergic drugs for administration through inhalation have been considered to have the possibility of aggravating dysuria associated with prostatic hyperplasia mediated by blood, and it has been demanded that the conventional anticholinergic drugs for administration through inhalation will have to show reduced side effects or adverse ractions. The present invention relates to a compound represented by the general formula (I): (wherein A represents; and R1, R2, R3 and R1 each a hydrogen atom or a substituent; R5 is a substituent; X- is an anion;the symbol: denotes an exo-form or endo-form, or their mixture), its salt or solvation product thereof. They are useful as a prophylactic and/or therapeutic agent with reduced side effects or adverse reactions for the diseases mediated by the muscarinic receptor.

  传统的抗胆碱药物通过吸入给药被认为可能加重与前列腺增生相关的排尿困难，并要求传统的抗胆碱药物通过吸入给药必须显示减少副作用或不良反应。 本发明涉及一种由通式（I）表示的化合物： （其中A代表; 和R1、R2、R3和R1分别是氢原子或取代基; R5是取代基; X-是阴离子;符号: 表示外向型或内向型，或它们的混合物），其盐或溶剂化产物。它们可用作通过胆碱受体介导的疾病的预防和/或治疗剂，具有减少副作用或不良反应。
• CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY
  申请人：Cerulean Pharma Inc.

  公开号：US20130196906A1

  公开（公告）日：2013-08-01

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  提供了关于使用CDP-治疗剂偶联物治疗疾病或紊乱的方法，例如自身免疫疾病、炎症性疾病、中枢神经系统紊乱、心血管疾病或代谢紊乱。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。
• [EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2005019228A1

  公开（公告）日：2005-03-03

  The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.

  本发明提供了具有抗菌活性的公式(I)和公式(II)的化合物及盐类：本发明还提供了用于制造公式(I)和公式(II)化合物的新的合成中间体。变量A1、R2、R3、R5、R6、R7、A8和R9在此文中定义。本文披露的某些公式(I)和公式(II)化合物是细菌DNA合成和细菌复制的强效和选择性抑制剂。本发明还提供了含有一种或多种公式(I)或公式(II)化合物以及一种或多种载体、辅料或稀释剂的抗菌组合物，包括药物组合物。这样的组合物可以只含有公式(I)或公式(II)的化合物作为唯一的活性成分，也可以含有公式(I)或公式(II)的化合物与一种或多种其他活性成分的组合。本发明还提供了用于治疗动物微生物感染的方法。
• DIAZENIUMDIOLATED NON-STEROIDAL ANTI-INFLAMMATORY DRUGS, COMPOSITIONS THEREOF, AND RELATED METHODS
  申请人：Velázquez Carlos A.

  公开号：US20090186859A1

  公开（公告）日：2009-07-23

  Disclosed are compounds that release nitric oxide, e.g., a compound of Formula (I) wherein R 1-10 , X, and n are as described herein, which are NSAID derivatives comprising a diazeniumdiolate moiety N 2 O 2 − . The compounds are chemopreventive agents with gastric-sparing, analgesic, cardioprotective, and/or anti-inflammatory properties. Also disclosed is a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable carrier. Also disclosed is a method of preventing or treating cancer or treating inflammation or an inflammation-related condition in a mammal comprising administering an effective amount of a compound of the invention to the mammal.

  披露了释放一氧化氮的化合物，例如，式(I)的化合物，其中R1-10、X和n如本文所述，这些化合物是非甾体抗炎药（NSAID）衍生物，包含亚硝基二醇基团N2O2−。这些化合物是具有胃保护、镇痛、心脏保护和/或抗炎特性的化学预防剂。还披露了一种药物组合物，包括本发明的化合物和药用载体。还披露了一种预防或治疗癌症或治疗炎症或炎症相关状况的方法，包括向哺乳动物施用本发明的化合物的有效量。
• COMPOSITIONS AND METHODS FOR TREATMENT OF AUTOIMMUNE AND OTHER DISEASE
  申请人：CERULEAN PHARMA INC.

  公开号：US20180193486A1

  公开（公告）日：2018-07-12

  Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of autoimmune disease, inflammatory disease, or cancer. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

  提供了关于使用CDP-治疗剂偶联物治疗自身免疫疾病、炎症性疾病或癌症的方法。还提供了CDP-治疗剂偶联物、包含CDP-治疗剂偶联物的颗粒以及包含CDP-治疗剂偶联物的组合物。