1,5-di-p-tolyl-3-(trifluoromethyl)-1H-pyrazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,5-di-p-tolyl-3-(trifluoromethyl)-1H-pyrazole
• 英文别名: 1,5-dip-tolyl-3-(trifluoromethyl)-1H-pyrazole；1,5-bis(4-methylphenyl)-3-(trifluoromethyl)pyrazole
• 化学式: C₁₈H₁₅F₃N₂
• 分子量: 316.326
• InChiKey: IUCYMYXIAQVGFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (E)-1,1,1,-trifluoro-4-(p-tolyl)but-3-en-2-one 在 copper(l) iodide 、 sodium acetate 、 potassium carbonate 、 对甲苯磺酰肼 、 N,N'-二甲基-1,2-环己二胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 12.0h， 生成 1,5-di-p-tolyl-3-(trifluoromethyl)-1H-pyrazole
  参考文献：
  名称：

  An efficient route to 3-trifluoromethylpyrazole via cyclization/1,5-H shift and its applications in the synthesis of bioactive compounds

  摘要：

  A methodology for regioselective synthesis of 3-trifluoromethylpyrazole from the reaction of trifluoromethyl alkenone and tosylhydrazone has been developed. The reaction was proposed to proceed through a tandem cyclization and 1,5-H shift reaction, which can be applied to the synthesis of bioactive compounds like Celecoxib, Mavacoxib, and SC-560. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.09.007

文献信息

• 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。
• CYCLOOXYGENASE-2 INHIBITOR/HISTONE DEACETYLASE INHIBITOR COMBINATION
  申请人：Chen Ying-Nan Pan

  公开号：US20080227845A1

  公开（公告）日：2008-09-18

  The invention relates to a combination which comprises (a) a cyclooxygenase-2 inhibitor (“COX-2 inhibitor”) and (b) a histone deacetylase inhibitor (“HDAI”) for simultaneous, concurrent, separate or sequential use, especially for use in the treatment of pre-malignant colon lesions or a colon cancer or other malignancies in a mammal, particularly a human. The invention also relates to pharmaceutical compositions comprising such a combination and to a method of treating pre-malignant colon lesions (e.g. polyps) and colon cancer, as well as other malignancies, in a mammal, particularly a human, with such a combination. The present invention further also relates to a commercial package or product comprising such a combination.

  本发明涉及一种组合物，包括（a）环氧合酶-2抑制剂（“COX-2抑制剂”）和（b）组蛋白去乙酰化酶抑制剂（“HDAI”），用于同时、并行、分离或顺序使用，特别是用于治疗哺乳动物，特别是人类的癌前结肠病变或结肠癌或其他恶性肿瘤。本发明还涉及包含这种组合物的制药组合物，以及使用这种组合物治疗癌前结肠病变（例如息肉）和结肠癌以及其他恶性肿瘤的方法。本发明还涉及包含这种组合物的商业包装或产品。
• Electrophotochemical Metal‐Catalyzed Decarboxylative Coupling of Aliphatic Carboxylic Acids
  作者：Kai Yang、Jiaqing Lu、Liubo Li、Sanzhong Luo、Niankai Fu

  DOI：10.1002/chem.202202370

  日期：2022.12.15

  Convergent paired metal electrocatalysis enables the direct use of simple primary and secondary aliphatic acids as coupling partners for C(sp2)−C(sp3) bond formation by radical decarboxylation. This new electrophotocatalytic method features a broad substrate scope, wide functional-group tolerance, and could be used for late-stage functionalization of complex molecules.

  收敛配对金属电催化能够直接使用简单的初级和次级脂肪酸作为通过自由基脱羧形成C(sp 2 )−C(sp 3 ) 键的偶联伙伴。这种新的电光催化方法具有广泛的底物范围和广泛的官能团耐受性，可用于复杂分子的后期功能化。
• PHARMACEUTICAL COMPOSITIONS OF CO-CRYSTALS OF TRAMADOL AND COXIBS
  申请人：LABORATORIOS DEL DR. ESTEVE, S.A.

  公开号：EP3158994A1

  公开（公告）日：2017-04-26

  The present invention relates to oral pharmaceutical compositions comprising co-crystals of tramadol and celecoxib, processes for preparation of the same and their use as medicaments, more particularly for the treatment of pain.

  本发明涉及由曲马多和塞来昔布的共晶体组成的口服药物组合物、其制备工艺及其作为药物的用途，特别是用于治疗疼痛。
• CYP2C9 Structure−Metabolism Relationships:  Optimizing the Metabolic Stability of COX-2 Inhibitors
  作者：Marie M. Ahlström、Marianne Ridderström、Ismael Zamora、Kristina Luthman

  DOI：10.1021/jm0705096

  日期：2007.9.1

  The cytochrome P450 (CYP) family is composed of a large group of monooxygenases that mediate the metabolism of xenobiotics and endogenous compounds. CYP2C9, one of the major isoforms of the CYP family, is responsible for the phase I metabolism of a variety of drugs. The aim of the present investigation is to use rational design together with MetaSite, a metabolism site prediction program, to synthesize compounds that retain their pharmacological effects but that are metabolically more stable in the presence of CYP2C9. The model compound for the study is the nonsteroidal anti-inflammatory drug celecoxib, a COX-2 selective inhibitor and known CYP2C9 substrate. Thirteen analogs of celecoxib were designed, synthesized, and evaluated with regard to their metabolic properties and pharmacologic effects. The docking solutions and the predictions from MetaSite gave useful information leading to the design of new compounds with improved metabolic properties.