4-(3-(tert-butyl)-5-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid | 1400633-31-9

• 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-(3-(tert-butyl)-5-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid
• 英文别名: 4-[5-Tert-butyl-3-(3,4-dichlorophenyl)-3,4-dihydropyrazol-2-yl]benzoic acid
• CAS: 1400633-31-9
• 化学式: C₂₀H₂₀Cl₂N₂O₂
• 分子量: 391.297
• InChiKey: IZCUZELGZSQULX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (E)-1-(3,4-dichlorophenyl)-4,4-dimethylpent-1-en-3-one 、 4-羧基苯肼盐酸盐 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以90%的产率得到4-(3-(tert-butyl)-5-(3,4-dichlorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid
  参考文献：
  名称：

  发现三取代吡唑啉作为开发选择性磷酸二酯酶 5 抑制剂的新型支架

  摘要：

  塞来昔布是一种选择性环氧合酶-2 (COX2) 抑制剂，具有 1,5-二芳基吡唑支架。与其他具有全身性高血压和血栓栓塞并发症副作用的 COX2 抑制剂相比，塞来昔布具有更好的安全性。这可能部分归因于涉及磷酸二酯酶 5 (PDE5) 抑制和 NO/cGMP 信号增强的脱靶活性，允许冠状血管舒张和主动脉舒张。受塞来昔布结构的启发，我们合成了一系列化学成分多样的化合物，其中包含 1,3,5-三取代的吡唑啉支架，以提高 PDE5 抑制效力，同时消除 COX2 抑制活性。PDE5 抑制的 SAR 研究揭示了 1-苯基上的羧酸官能团的重要作用，以及非平面吡唑啉核心在平面吡唑上的重要性，5-苯基部分可以耐受一系列取代基。这些修改导致新的 PDE5 抑制剂与塞来昔布相比，抑制 PDE5 的效力提高了大约 20 倍，并且没有 COX-2 抑制活性。化合物的 PDE 同工酶分析图 11显示了良好的选择性。这些

  DOI：

  10.1016/j.bioorg.2020.104322

文献信息

• [EN] DERIVATIVES OF CELECOXIB, USE THEREOF AND PREPARATION THEREOF<br/>[FR] DÉRIVÉS DE CÉLÉCOXIB, LEUR UTILISATION ET LEUR PRÉPARATION
  申请人：SOUTHERN RES INST

  公开号：WO2012125884A1

  公开（公告）日：2012-09-20

  Derivatives of celecoxib that lack cyclooxygenase inhibitory activity but have improved PDE5 inhibitory activity are provided along with pharmaceutical compositions containing them for the treatment or prevention of cancer. Such compounds are expected to have reduced toxicity compared with celecoxib and other cyclooxygenase inhibitors, and greater efficacy compared with conventional PDE5 inhibitors. Derivatives of celecoxib are also suitable for treating chronic inflammatory conditions, erectile dysfunction, pulmonary hypertension, congestive heart failure, and enhancement of cognitive function.

  提供了缺乏环氧合酶抑制活性但具有改善PDE5抑制活性的Celecoxib衍生物，以及包含它们的药物组合物，用于治疗或预防癌症。这些化合物预计与Celecoxib和其他环氧合酶抑制剂相比，具有减少的毒性，并与传统的PDE5抑制剂相比具有更大的疗效。Celecoxib的衍生物也适用于治疗慢性炎症性疾病、勃起功能障碍、肺动脉高压、充血性心力衰竭和增强认知功能。
• AIR CONDITIONING SYSTEM
  申请人：Suzuki Yoshinobu

  公开号：US20140165838A1

  公开（公告）日：2014-06-19

  As a permeable membrane of an air conditioning system that performs as supply to a space to be air conditioned through the permeable membrane and/or gas discharge from the space to be air conditioned through the permeable membrane, an asymmetric membrane is used. The asymmetric membrane is made of a cyclic olefin addition polymer obtained by addition polymerization of a cyclic olefin functionality siloxane, or by addition polymerization of the cyclic olefin functionality siloxane and a cyclic olefin compound, and in which a rate of a structural unit derived from the cyclic olefin functionality siloxane is 5 to 100 mol % of the addition polymer, and a number average molecular weight (Mn) is 10,000 to 2,000,000 in terms of polystyrene conversion measured by a GPC using tetrahydrofuran as a solvent.
• DERIVATIVES OF CELEBOXIB, USE THEREOF AND PREPARATION THEREOF
  申请人：Piazza Gary A.

  公开号：US20140171477A1

  公开（公告）日：2014-06-19

  Derivatives of celecoxib that lack cyclooxygenase inhibitory activity but have improved PDE5 inhibitory activity are provided along with pharmaceutical compositions containing them for the treatment or prevention of cancer. Such compounds are expected to have reduced toxicity compared with celecoxib and other cyclooxygenase inhibitors, and greater efficacy compared with conventional PDE5 inhibitors. Derivatives of celecoxib are also suitable for treating chronic inflammatory conditions, erectile dysfunction, pulmonary hypertension, congestive heart failure, and enhancement of cognitive function.
• US8999043B2
  申请人：——

  公开号：US8999043B2

  公开（公告）日：2015-04-07
• US9388139B2
  申请人：——

  公开号：US9388139B2

  公开（公告）日：2016-07-12