4-((2-hydroxy-3-methoxybenzyl)amino)-N-(5-phenylthiazol-2-yl)benzenesulfonamide | 1532593-40-0

• 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: 4-((2-hydroxy-3-methoxybenzyl)amino)-N-(5-phenylthiazol-2-yl)benzenesulfonamide
• 英文别名: 4-[(2-hydroxy-3-methoxyphenyl)methylamino]-N-(5-phenyl-1,3-thiazol-2-yl)benzenesulfonamide
• CAS: 1532593-40-0
• 化学式: C₂₃H₂₁N₃O₄S₂
• 分子量: 467.569
• InChiKey: TVRYXKQZKQZCAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氨基-5-苯基噻唑 在 吡啶 、 sodium tetrahydroborate 、 palladium 10% on activated carbon 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙酸乙酯 为溶剂， 20.0~100.0 ℃ 、5.0 MPa 条件下， 反应 18.0h， 生成 4-((2-hydroxy-3-methoxybenzyl)amino)-N-(5-phenylthiazol-2-yl)benzenesulfonamide
  参考文献：
  名称：

  4-（（2-羟基-3-甲氧基苄基）氨基）苯磺酰胺衍生物作为 12-脂氧化酶的强效和选择性抑制剂的合成和构效关系研究

  摘要：

  人类脂肪氧化酶 (LOX) 是一类含铁酶，可催化多不饱和脂肪酸氧化以提供相应的生物活性羟基二十碳四烯酸 (HETE) 代谢物。这些类二十烷酸信号分子参与了许多生理反应，例如血小板聚集、炎症和细胞增殖。我们小组对血小板型 12-( S )-LOX (12-LOX)产生了特别的兴趣，因为它在皮肤病、糖尿病、血小板止血、血栓形成和癌症中发挥了重要作用。在此，我们报告了基于 4-（（2-羟基-3-甲氧基苄基）氨基）苯磺酰胺的支架的鉴定和药物化学优化。顶级化合物，以35和36为例, 显示对 12-LOX 的 nM 效力，对相关脂肪氧化酶和环氧化酶具有出色的选择性，并具有良好的 ADME 特性。此外，这两种化合物均抑制 PAR-4 诱导的人血小板聚集和钙动员，并减少 β 细胞中的 12-HETE。

  DOI：

  10.1021/jm4016476

文献信息

• [EN] 4-((2-HYDROXY-3-METHOXYBENZYL)AMINO) BENZENESULFONAMIDE DERIVATIVES AS 12-LIPOXYGENASE INHIBITORS<br/>[FR] DÉRIVÉS DE 4-((2-HYDROXY-3-MÉTHOXYBENZYL)AMINO)BENZÈNESULFONAMIDE COMME INHIBITEUR DE LA 12-LIPOXYGÉNASE
  申请人：EASTERN VIRGINIA MED SCHOOL

  公开号：WO2015054662A1

  公开（公告）日：2015-04-16

  Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3- methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells. The compounds can also be used in methods for treating or preventing a 12- lipoxygenase mediated disease or disorder.

  人类脂氧合酶（LOXs）是一类含铁酶的家族，参与催化多不饱和脂肪酸的氧化，提供相应的生物活性羟基二十碳四烯酸（HETE）代谢产物。这些花生四烯酸信号分子参与许多生理反应，如血小板聚集、炎症和细胞增殖。血小板型12-（S）-LOX（12-LOX）因其在皮肤疾病、糖尿病、血小板止血、血栓形成和癌症中的已知作用而特别引起关注。本文揭示了基于4-（（2-羟基-3-甲氧基苯基）氨基）苯磺酰胺骨架的鉴定和药物化学优化。这些化合物对12-LOX具有纳摩尔级的效力，并且对相关的脂氧合酶和环氧合酶具有良好的选择性。除了具有良好的ADME性质外，这些化合物还可以抑制PAR-4诱导的人类血小板聚集和钙离子动员，并减少小鼠/人类β细胞中的12-HETE。这些化合物还可以用于治疗或预防12-脂氧合酶介导的疾病或紊乱的方法。
• 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase
  申请人：Eastern Virginia Medical School

  公开号：US10266488B2

  公开（公告）日：2019-04-23

  Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells. The compounds can also be used in methods for treating or preventing a 12-lipoxygenase mediated disease or disorder.

  人类脂氧合酶（LOXs）是一个含铁酶家族，参与催化多不饱和脂肪酸的氧化，以提供相应的具有生物活性的羟基二十碳四烯酸（HETE）代谢物。这些类二十碳烷烃信号分子参与了许多生理反应，如血小板聚集、炎症和细胞增殖。血小板型 12-(S)-LOX（12-LOX）尤其令人感兴趣，因为它在皮肤病、糖尿病、血小板止血、血栓形成和癌症中的作用已得到证实。本文公开了 4-((2-羟基-3-甲氧基苄基)氨基)苯磺酰胺基支架的鉴定和药物化学优化。这些化合物对 12-LOX 具有 nM 效能，对相关脂氧合酶和环氧合酶具有极佳的选择性。除了具有良好的 ADME 特性外，这些化合物还能抑制 PAR-4 诱导的人血小板聚集和钙动员，并减少小鼠/人 beta 细胞中的 12-HETE。这些化合物还可用于治疗或预防 12-脂氧合酶介导的疾病或紊乱。
• 4-((2-HYDROXY-3-METHOXYBENZYL)AMINO) BENZENESULFONAMIDE DERIVATIVES AS 12-LIPOXYGENASE INHIBITORS
  申请人：Eastern Virginia Medical School

  公开号：EP3054936A1

  公开（公告）日：2016-08-17
• 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide Derivatives as Potent and Selective Inhibitors of 12-Lipoxygenase
  申请人：EASTERN VIRGINIA MEDICAL SCHOOL

  公开号：US20170001955A1

  公开（公告）日：2017-01-05

  Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells. The compounds can also be used in methods for treating or preventing a 12-lipoxygenase mediated disease or disorder.
• 4-((2-HYDROXY-3-METHOXYBENZYL)AMINO)BENZENESULFONAMIDE DERIVATIVES AS POTENT AND SELECTIVE INHIBITORS OF 12-LIPOXYGENASE
  申请人：Eastern Virginia Medical School

  公开号：US20190276395A1

  公开（公告）日：2019-09-12

  Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells. The compounds can also be used in methods for treating or preventing a 12-lipoxygenase mediated disease or disorder.