methyl 4-chloroacetamidosalicylate | 14035-08-6

• 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: methyl 4-chloroacetamidosalicylate
• 英文别名: methyl 4-2-chloroacetamido-2-hydroxybenzoate；N-Monochloracetyl-p-aminosalicylsaeure-methylester；4-Chloracetamino-salicylsaeure-methylester；Methyl 4-[(2-chloroacetyl)amino]-2-hydroxybenzoate；methyl 4-[(2-chloroacetyl)amino]-2-hydroxybenzoate
• CAS: 14035-08-6
• 化学式: C₁₀H₁₀ClNO₄
• 分子量: 243.647
• InChiKey: IJUAAMSFNGESFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-chloroacetamidosalicylate 在 sodium acetate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 26.0h， 生成 methyl 2-hydroxy-4-[(5-(Z)-(3-thienylmethylidene)-4(H)-oxo-1,3-thiazol-2-yl)amino]benzoate
  参考文献：
  名称：

  Conjugation of 4-aminosalicylate with thiazolinones afforded non-cytotoxic potent in vitro and in vivo anti-inflammatory hybrids

  摘要：

  Eicosanoids like leukotrienes and prostaglandins that produced within the arachidonic acid cascade are involved in the pathogenesis of pain, acute and chronic inflammatory diseases. A promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Aiming to develop balanced COX/LOX inhibitors; 4-aminosalicylate based thiazolinones having different substituents at the 5th position of the 4-thiazolinone ring (2-22) were designed, synthesized, characterized and evaluated in vitro and in vivo for their anti-inflammatory activity. Most of the investigated compounds showed high COX-2 inhibitory potencies (IC(50)( )39-200 mu M) with selectivity indexes (30-84). Two compounds, 19 and 21, (IC50 = 41 and 44 mu M), are equipotent to celecoxib (IC50, = 49 mu M), while compound 22 (IC50 = 39 mu M) was the most potent. For 15-LOX, compounds 5, 11, 19, 21 and 22 revealed higher potency (IC50 1.5-2.2 mu M) than zileuton (IC50 15 mu M). Thus, compounds 5, 11, 19, 21 and 22 are potent dual inhibitors of COX-2 and 15-LOX. In vivo anti-inflammatory testing of these compounds revealed that, compounds 5 and 21 had an anti-inflammatory activity similar to indomethacin and celecoxib (% inhibition of oedema = 60 +/- 9) and higher than diclofenac potassium (% inhibition = 52 +/- 29), while compound 22 (% inhibition = 63 +/- 5) was more active than the reference drugs. The results showed that the activity is controlled by the bulkiness and lipophilicity of the substituent at the 5th position. The cytotoxicity results revealed that all compounds are not cytotoxic, additionally, in an experimental model of ulcerogenic effect, the most active compounds 21 and 22 showed better safety profile than indomethacin. Further, at the active sites of the COX-1, COX-2 and 15-LOX co-crystal, 19, 21, and 22 showed high binding forces in free binding energy study, which is consistent with in vitro and in vivo results. In conclusion, these compounds are good candidates for further biological investigation as potential anti-inflammatory drugs with dual balanced inhibition of COX and 15-LOX and good safety profile.

  DOI：

  10.1016/j.bioorg.2019.103378
• 作为产物：
  描述：

  4-氨基水杨酸 在 硫酸 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 4-chloroacetamidosalicylate
  参考文献：
  名称：

  对氨基水杨酸氟喹诺酮类衍生物及其中间体、制备方法和应用

  摘要：

  本发明公开了对氨基水杨酸氟喹诺酮类衍生物及其中间体、制备方法和应用，属于药物合成技术领域；对氨基水杨酸氟喹诺酮类衍生物的结构式如下；体外活性测定结果表明，部分对氨基水杨酸氟喹诺酮类衍生物(简称化合物)及中间体对耻垢分枝杆菌均有抑制作用；化合物及中间体对常见致病菌的抑制活性整体较好；绝大多数化合物和中间体对毕赤酵母菌的抑菌活性整体较好；部分化合物对柑橘溃疡病菌的抑制活性较好；本发明的对氨基水杨酸氟喹诺酮类衍生物及其中间体在抗结核、抗细菌、抗真菌和抗柑橘病菌领域均具有潜在的应用前景。

  公开号：

  CN112159355B

文献信息

• 对氨基水杨酸唑类衍生物及其制备方法和应用
  申请人：西南大学

  公开号：CN112028833B

  公开（公告）日：2022-07-05

  本发明公开了对氨基水杨酸唑类衍生物及其制备方法和应用，属于药物合成技术领域。对氨基水杨酸唑类衍生物的结构式如下。抗菌活性测定结果表明，本发明的对氨基水杨酸唑类衍生物对常见致病菌抑制活性整体很好，部分分子对毕赤酵母菌的抑菌活性强于或相当于阳性药物氟康唑，所有分子对柑橘胶孢炭疽病菌的抑制活性较好、部分分子与阳性对照咪鲜胺的抑制活性相当或更强，多数分子对柑橘溃疡病菌具有良好的抑制作用。抗肿瘤细胞活性测定结果显示，本发明的对氨基水杨酸唑类衍生物对三种肿瘤细胞均有抑制作用。本发明的对氨基水杨酸唑类衍生物在抗细菌、抗真菌、抗柑橘病菌和抗肿瘤领域具有潜在的应用前景。
• Synthesis, biological evaluation and molecular docking study of some new 4-aminosalicylic acid derivatives as anti-inflammatory and antimycobacterial agents
  作者：Maha Q.M. Qahtan、Etify A. Bakhite、Jyothi kumari、Ahmed M. Sayed、Mahmoud Kandeel、Dharmarajan Sriram、Hajjaj H.M. Abdu-Allah

  DOI：10.1016/j.bioorg.2023.106344

  日期：2023.3

  In this study, new derivatives of the antitubercular and anti-inflammatory drug, 4-aminosaliclic acids (4-ASA) were synthesized, characterized, and evaluated for these activities. In vivo and in viro evaluation of anti-inflammatory activity revealed that compounds 10, 19 and 20 are the most active with potent cyclooxygenase-2 (COX-2) and 5-lipooxgenase (5-LOX) inhibition and without causing gasric

  在这项研究中，抗结核和抗炎药物 4-氨基水杨酸 (4-ASA) 的新衍生物被合成、表征并评估了这些活性。抗炎活性的体内和体外评估表明，化合物10、19和20具有最强的环氧合酶 2 (COX-2) 和 5-脂氧合酶 (5-LOX) 抑制活性，并且不会引起胃损伤。还测量了新合成化合物对结核分枝杆菌H37RV 的最低抑制浓度 (MIC)。供试化合物17 , 19和20表现出显着的抗结核分枝杆菌生长的活性。20是最有效的，其 (MIC 1.04 µM) 比母体药物 4-ASA 强 2.5 倍。20显示出对正常细胞的低细胞毒性，提供了高治疗指数。通过对接和结构-活性关系分析来分析重要的结构特征，以更好地了解预测抗炎和抗结核活性的结构决定因素。我们的结果表明，化合物19和20是发现双重抗炎和抗结核候选药物的潜在先导化合物。
• 以对氨基水杨酸为母核的三分子缀合物、中间体、制备方法及用途
  申请人：西南大学

  公开号：CN114478486B

  公开（公告）日：2023-07-25

  本发明公开了式I所示的以对氨基水杨酸(PAS)为母核的三分子缀合物，是由PAS、异烟酸和氟喹诺酮这三种结构单元缀合而成；经抗人致病菌活性测试，本发明合成的三分子缀合物均具有一定的抗细菌活性，尤其存在对结核分枝杆菌、沙门氏菌、铜绿假单胞菌、金黄色葡萄球菌具有高抑菌活性的多个分子，同时溶血性测试验证了分子的安全性，具有进一步开发研制抗细菌药物尤其是抗结核药物的潜力。
• Conjugation of 4-aminosalicylate with thiazolinones afforded non-cytotoxic potent in vitro and in vivo anti-inflammatory hybrids
  作者：Hajjaj H.M. Abdu-Allah、Alshaimaa A.B. Abdelmoez、Hamadeh Tarazi、Abdel-Nasser A. El-Shorbagi、Raafat El-Awady

  DOI：10.1016/j.bioorg.2019.103378

  日期：2020.1

  Eicosanoids like leukotrienes and prostaglandins that produced within the arachidonic acid cascade are involved in the pathogenesis of pain, acute and chronic inflammatory diseases. A promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Aiming to develop balanced COX/LOX inhibitors; 4-aminosalicylate based thiazolinones having different substituents at the 5th position of the 4-thiazolinone ring (2-22) were designed, synthesized, characterized and evaluated in vitro and in vivo for their anti-inflammatory activity. Most of the investigated compounds showed high COX-2 inhibitory potencies (IC(50)( )39-200 mu M) with selectivity indexes (30-84). Two compounds, 19 and 21, (IC50 = 41 and 44 mu M), are equipotent to celecoxib (IC50, = 49 mu M), while compound 22 (IC50 = 39 mu M) was the most potent. For 15-LOX, compounds 5, 11, 19, 21 and 22 revealed higher potency (IC50 1.5-2.2 mu M) than zileuton (IC50 15 mu M). Thus, compounds 5, 11, 19, 21 and 22 are potent dual inhibitors of COX-2 and 15-LOX. In vivo anti-inflammatory testing of these compounds revealed that, compounds 5 and 21 had an anti-inflammatory activity similar to indomethacin and celecoxib (% inhibition of oedema = 60 +/- 9) and higher than diclofenac potassium (% inhibition = 52 +/- 29), while compound 22 (% inhibition = 63 +/- 5) was more active than the reference drugs. The results showed that the activity is controlled by the bulkiness and lipophilicity of the substituent at the 5th position. The cytotoxicity results revealed that all compounds are not cytotoxic, additionally, in an experimental model of ulcerogenic effect, the most active compounds 21 and 22 showed better safety profile than indomethacin. Further, at the active sites of the COX-1, COX-2 and 15-LOX co-crystal, 19, 21, and 22 showed high binding forces in free binding energy study, which is consistent with in vitro and in vivo results. In conclusion, these compounds are good candidates for further biological investigation as potential anti-inflammatory drugs with dual balanced inhibition of COX and 15-LOX and good safety profile.
• 对氨基水杨酸氟喹诺酮类衍生物及其中间体、制备方法和应用
  申请人：西南大学

  公开号：CN112159355B

  公开（公告）日：2022-06-24

  本发明公开了对氨基水杨酸氟喹诺酮类衍生物及其中间体、制备方法和应用，属于药物合成技术领域；对氨基水杨酸氟喹诺酮类衍生物的结构式如下；体外活性测定结果表明，部分对氨基水杨酸氟喹诺酮类衍生物(简称化合物)及中间体对耻垢分枝杆菌均有抑制作用；化合物及中间体对常见致病菌的抑制活性整体较好；绝大多数化合物和中间体对毕赤酵母菌的抑菌活性整体较好；部分化合物对柑橘溃疡病菌的抑制活性较好；本发明的对氨基水杨酸氟喹诺酮类衍生物及其中间体在抗结核、抗细菌、抗真菌和抗柑橘病菌领域均具有潜在的应用前景。