(S)-5-ethyl-5-methyl-3-(1-methylethoxy)-4-[(4-methylsulfonyl)phenyl]-3-oxolen-2-one | 189954-93-6

• 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: (S)-5-ethyl-5-methyl-3-(1-methylethoxy)-4-[(4-methylsulfonyl)phenyl]-3-oxolen-2-one
• 英文别名: (5S)-5-ethyl-3-isopropoxy-5-methyl-4-[4-(methylsulfonyl)phenyl]furan-2(5H)-one；(S)-5-ethyl-3-isopropoxy-5-methyl-4-[4-(methylsulfonyl)phenyl]furan-2(5H)-one；(5S)-ethyl-5-methyl-4-(4-(methanesulfonyl)phenyl)-3-(2-propoxy)-(5H)-furan-2-one；(5S) 5-ethyl-5-methyl-4-(4-(methylsulfonyl)phenyl)-3-(2-propoxy)-5H-furan-2-one；5(S)-5-ethyl-5-methyl-4-(4-(methylsulfonyl)phenyl)-3-(2-propoxy)-5H-furan-2-one；5(S)-ethyl-5-methyl-4-(4-(methylsulfonyl)phenyl)-3-(2-propoxy)-5H-furan-2-one；5-Ethyl-3-isopropoxy-4-(4-methanesulfonyl-phenyl)-5-methyl-5H-furan-2-one；(5S)-5-ethyl-5-methyl-4-(4-methylsulfonylphenyl)-3-propan-2-yloxyfuran-2-one
• CAS: 189954-93-6
• 化学式: C₁₇H₂₂O₅S
• 分子量: 338.425
• InChiKey: FZYAFLPJDVKKQI-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  5

制备方法与用途

COX-2-IN-36（化合物1）是一种非常有效的、特异性的COX-2抑制剂，其IC50值为0.4 μM。

反应信息

• 作为反应物：
  描述：

  (S)-5-ethyl-5-methyl-3-(1-methylethoxy)-4-[(4-methylsulfonyl)phenyl]-3-oxolen-2-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以95%的产率得到(5S)-5-ethyl-3-isopropoxy-5-methyl-4-[4-(methylsulfonyl)phenyl]furan-2(5H)-thione
  参考文献：
  名称：

  Water soluble prodrugs of COX-2 inhibitors

  摘要：

  揭示了作为COX-2抑制剂的前药有用的水溶性化合物，以及包含它们的药物组合物。

  公开号：

  US20060189682A1
• 作为产物：
  描述：

  (S)-2-hydroxy-2-methyl-1-(pyrrolidin-1-yl)butan-1-one 在 4-二甲氨基吡啶 、 sodium tungstate 、 正丁基锂 、 三氟乙酸异丙酯 、 三苯基甲烷 、 双氧水 、 三甲基乙酰氯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 、 乙腈 为溶剂， 反应 3.5h， 生成 (S)-5-ethyl-5-methyl-3-(1-methylethoxy)-4-[(4-methylsulfonyl)phenyl]-3-oxolen-2-one
  参考文献：
  名称：

  实用的COX-2特异性抑制剂的对映选择性合成

  摘要：

  已经描述了COX-2特异性抑制剂1的两种合成策略，其允许以（S）-2-羟基-2-甲基丁酸的79％的总产率大量制备。这些研究已导致鉴定出（±）-2-羟基-2-甲基丁酸的有效拆分和新型亚硫酰氯辅助从酸6形成酰胺11的方法。

  DOI：

  10.1016/s0040-4020(02)00826-8

文献信息

• Combination therapy using COX-2 selective inhibitor and thromboxane inhibitor and compositions therefor
  申请人：——

  公开号：US20020016342A1

  公开（公告）日：2002-02-07

  The present invention provides a method for the treatment or prophylaxis of COX-2-mediated conditions in patients who are at risk of developing thromboembolic events which comprises administering to said patient a therapeutically or prophylactically effective amount of a COX-2 selective inhibitor and a cardiovascular protective amount of a thromboxane inhibitor, as well as compositions therefor.

  本发明提供了一种治疗或预防COX-2介导的病症的方法，适用于有发生血栓栓塞事件风险的患者，包括向该患者施用治疗或预防有效量的COX-2选择性抑制剂和心血管保护量的血栓素抑制剂，以及相应的组合物。
• Methods for treating or reducing the risk of pain and inflammatory disorders by administering inhibitors of activated thrombin activatable fibrinolysis inhibitor
  申请人：——

  公开号：US20030035795A1

  公开（公告）日：2003-02-20

  The invention includes methods for treating or reducing the risk of inflammation in a patient which comprises treating the patient with an inhibitor of activated thrombin activatable fibrinolysis inhibitor. Such diseases include but are not limited to nephritis, systemic lupus erythematosus, rheumatoid arthritis, glomerulonephritis, and sacoidosis. The invention includes methods for treating or reducing the risk of pain in a patient which comprises treating the patient with an inhibitor of activated thrombin activatable fibrinolysis inhibitor. In one class of these methods, the inhibitor of activated thrombin activatable fibrinolysis inhibitor is selected from the group consisting of 2-(6-amino-pyridin-3-ylmethyl)-3-butyl-succinic acid, 2-(6-amino-pyridin-3-ylmethyl)-3-phenethyl-succinic acid, 2-(6-amino-pyridin-3-ylmethyl)-3-methyl-succinic acid, 2-(6-amino-5-methyl-pyridin-3-ylmethyl)-3-[(1-benzyloxycarbonylamino-2-methyl-propyl)hydroxy-phosphinoyl]-propionic acid, 2-(6-amino-pyridin-3-ylmethyl)-3-[hydroxy-(3-phenyl-propyl)-phosphinoyl]-propionic acid, 2-(amino-pyridin-3-ylmethyl)-N-hydroxy-succinamic acid, 3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-propionic acid, 2-(2-amino-pyridin-4-ylmethyl)-3-mercapto-propionic acid, 2-(6-amino-pyridin-3-ylmethyl)-2-mercaptomethyl-butyric acid, 3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid, 3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid, 3-(6-amino-4-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid, and 3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-butyric acid or a pharmaceutically acceptable salt thereof. The invention is also a method for treating or reducing the risk of inflammation in a patient, or treating or reducing the risk of pain, which comprises treating the patient with a composition comprising an inhibitor of activated thrombin activatable fibrinolysis inhibitor and an NSAID, e.g., a COX-2 inhibitor. Such diseases include but are not limited to nephritis, systemic lupus, erythematosus, rheumatoid arthritis, glomerulonephritis, and sacoidosis.

  该发明涉及治疗或减少患者炎症风险的方法，包括使用活化凝血酶活化的纤溶抑制剂治疗患者。这些疾病包括但不限于肾炎、系统性红斑狼疮、类风湿关节炎、肾小球肾炎和结节病。该发明还涉及治疗或减少患者疼痛风险的方法，包括使用活化凝血酶活化的纤溶抑制剂治疗患者。在这些方法的一类中，活化凝血酶活化的纤溶抑制剂选择自2-(6-氨基吡啶-3-基甲基)-3-丁基琥珀酸、2-(6-氨基吡啶-3-基甲基)-3-苯乙基琥珀酸、2-(6-氨基吡啶-3-基甲基)-3-甲基琥珀酸、2-(6-氨基-5-甲基吡啶-3-基甲基)-3-[(1-苄氧羰基氨基-2-甲基-丙基)羟基磷酰基]-丙酸、2-(6-氨基吡啶-3-基甲基)-3-[羟基-(3-苯基-丙基)-磷酰基]-丙酸、2-(氨基吡啶-3-基甲基)-N-羟基琥酰胺酸、3-(6-氨基吡啶-3-基)-2-巯基甲基丙酸、2-(2-氨基吡啶-4-基甲基)-3-巯基丙酸、2-(6-氨基吡啶-3-基甲基)-2-巯基甲基丁酸、3-(6-氨基-5-甲基吡啶-3-基)-2-巯基甲基-2-甲基丙酸、3-(6-氨基-5-甲基吡啶-3-基)-2-巯基甲基丙酸、3-(6-氨基-4-甲基吡啶-3-基)-2-巯基甲基丙酸和3-(6-氨基吡啶-3-基)-2-巯基甲基丁酸或其药学上可接受的盐。该发明还是一种治疗或减少患者炎症风险，或治疗或减少疼痛风险的方法，包括使用含有活化凝血酶活化的纤溶抑制剂和NSAID（例如COX-2抑制剂）的组合物治疗患者。这些疾病包括但不限于肾炎、系统性红斑狼疮、类风湿关节炎、肾小球肾炎和结节病。
• Use of a COX-2 inhibitor and a NK-1 receptor antagonist for treating inflammation
  申请人：——

  公开号：US20040097573A1

  公开（公告）日：2004-05-20

  The present invention provides the use of a COX-2 inhibitior and an NK-1 receptor antagonist for the treatment or prevention of inflammatory disorders.

  本发明提供了利用COX-2抑制剂和NK-1受体拮抗剂用于治疗或预防炎症性疾病的方法。
• Combination therapy for treating neurodegenerative disease
  申请人：——

  公开号：US20020115689A1

  公开（公告）日：2002-08-22

  The instant invention provides a novel drug combination comprised of an HMG-CoA reductase inhibitor and a selective COX-2 inhibitor, which is useful for treating, preventing, delaying the onset of and/or reducing the risk of developing Alzheimer's disease. One object of the instant invention is to administer the above-described combination therapy to people who do not yet show clinical signs of Alzheimer's disease, but who are at risk of developing Alzheimer's disease. These individuals may already show signs of mild cognitive impairment. Toward this end, the instant invention provides methods for preventing or reducing the risk of developing Alzheimer's by administering the above-described combination therapy to said at risk persons. Such treatment may halt or reduce the rate of further cognitive decline or, in fact, reverse cognitive decline. The present invention also provides for a method of preventing cognitive impairment or dementia, reducing the risk of cognitive decline or impairment or reducing cognitive decline or impairment resulting from stroke, stroke, cerebral ischemia or de-myelinating disorders.

  本发明提供了一种新颖的药物组合，包括HMG-CoA还原酶抑制剂和选择性COX-2抑制剂，用于治疗、预防、延缓阿尔茨海默病的发作和/或减少发展阿尔茨海默病的风险。本发明的一个目的是将上述所述的组合疗法用于尚未表现出阿尔茨海默病临床症状，但处于患阿尔茨海默病风险的人群。这些个体可能已经表现出轻度认知障碍的迹象。为此，本发明提供了通过向上述风险人群施用上述组合疗法来预防或减少发展阿尔茨海默病的方法。这种治疗可能会阻止或减少进一步的认知下降速度，或者实际上逆转认知下降。本发明还提供了一种预防认知障碍或痴呆、减少认知下降或障碍风险或减少由中风、脑卒中、脑缺血或脱髓鞘性疾病导致的认知下降或障碍的方法。
• Base-catalyzed deuterium and tritium labeling of aryl methyl sulfones
  作者：John Scheigetz、Carl Berthelette、Chun Li、Robert J. Zamboni

  DOI：10.1002/jlcr.880

  日期：2004.10.30

  for conveniently tritiating the aryl methyl sulfones of compounds identified as potent and selective inhibitors of human Cox-2 and as DP receptor antagonists. A base-catalyzed exchange reaction was conducted with deuterated water and the total deuterium incorporation, ranging from 46 to 99%, was calculated using mass spectrometry. Results from these exchanges were used as guidelines for tritium labeling

  提出了一种用于方便地氚化被鉴定为人 Cox-2 的有效和选择性抑制剂和 DP 受体拮抗剂的化合物的芳基甲基砜的方法。用氘水进行碱催化交换反应，并使用质谱法计算出总氘掺入量，范围为 46% 至 99%。这些交换的结果被用作氚标记的指南，给出 28–120 mCi/mmol (1.03–4.43 GBq/mmol) 范围内的特定放射性。版权所有 © 2004 John Wiley & Sons, Ltd.