5-(4-叔丁基苯基)-1H-吡唑-3-羧酸 | 852816-01-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(4-叔丁基苯基)-1H-吡唑-3-羧酸
• 英文名称: 5-(4-tert-butylphenyl)-1H-pyrazole-3-carboxylic acid
• 英文别名: 5-[4-(1,1-dimethylethyl)phenyl]-1H-pyrazole-3-carboxylic acid；3-(4-tert-butylphenyl)-1H-pyrazole-5-carboxylic acid
• CAS: 852816-01-4
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: YKSQTHUPPONYBR-UHFFFAOYSA-N

物化性质

• 沸点：
  467.1±33.0 °C(Predicted)
• 密度：
  1.188±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-叔丁基苯基)-1H-吡唑-3-羧酸 在 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  [EN] SUBSTITUTED PYRAZOLES AS PPAR AGONISTS
  [FR] PYRAZOLES SUBSTITUES UTILISES EN TANT QU'AGONISTES DE PPAR

  摘要：

  式（I）的化合物及其药学上可接受的盐、溶剂化合物和可水解酯（I）其中：p为O或1；q为O或1；R1和R2独立地为H或C1-3烷基；R3和R4独立地为H、C1-6烷基、-OC1-6烷基、卤素、OH、C2-6烯基或CF3；R5为H、C1-6烷基（可选地被一个或多个卤素、-CO苯基、OC1-6烷基、苯基吗啡啉或C2-6烯基取代）。R6为C1-6烷基、卤素、-OCH2苯基、苯基（可选地被C1-3烷基取代）、吗啡啉、吡咯啉、哌啶、噻吩基、呋喃基吡啶基或-OC2-6烯基。这些化合物激活hppar受体的α和γ亚型，在糖尿病、血脂异常或X综合征的治疗中很有用。

  公开号：

  WO2005049578A1
• 作为产物：
  描述：

  对叔丁基苯乙酮 在 sodium methylate 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 15.0h， 生成 5-(4-叔丁基苯基)-1H-吡唑-3-羧酸
  参考文献：
  名称：

  5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII

  摘要：

  Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4-50 mu M). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho-and meta-positions inhibited hCA IX with Kis ranging between 5 and 25 mu M. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.052

文献信息

• Substituted Pyrazoles As Ppar Agonists
  申请人：Faucher Eric Nicolas

  公开号：US20080021030A1

  公开（公告）日：2008-01-24

  A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof wherein: p is 0 or 1; q is 0 or 1; R 1 and R 2 are independently H or C 1-3 alkyl; R 3 and R 4 are independently H, C 1-6 alkyl, —OC 1-6 alkyl, halogen, OH, C 2-6 alkenyl or CF 3 ; R 5 is H, or C 1-6 alkyl, wherein said C 1-6 alkyl is optionally substituted by one or more halogens, —COphenyl, —OC 1-6 alkyl, phenyl, morpholino, or C 2-6 alkenyl; R 6 is C 1-6 alkyl, halogen, —OCH 2 phenyl, morpholino, pyrrolidino, piperidino, thiophenyl, furanyl, pyridinyl, —OC 2-6 alkenyl, or phenyl, wherein said phenyl is optionally substituted by C 1-3 alkyl.

  化合物的分子式为（I），其药学上可接受的盐、溶剂化物和可水解酯类，其中：p为0或1；q为0或1；R1和R2独立地为H或C1-3烷基；R3和R4独立地为H、C1-6烷基、—OC1-6烷基、卤素、OH、C2-6烯基或CF3；R5为H或C1-6烷基，其中所述的C1-6烷基可以选用一个或多个卤素、—CO苯基、—OC1-6烷基、苯基、吗啉基或C2-6烯基进行取代；R6为C1-6烷基、卤素、—OCH2苯基、吗啉基、吡咯烷基、哌啶基、噻吩基、呋喃基、吡啶基、—OC2-6烯基或苯基，其中所述的苯基可以选用C1-3烷基进行取代。
• [EN] COMPOUND AND USE THEREOF IN PREPARATION OF BCL-XL INHIBITOR<br/>[FR] COMPOSÉ ET SON UTILISATION DANS LA PRÉPARATION D'UN INHIBITEUR DE BCL-XL<br/>[ZH] 一种化合物及其在制备BCL-XL抑制剂中的用途
  申请人：[en]HITGEN INC.;[zh]成都先导药物开发股份有限公司

  公开号：WO2023236814A1

  公开（公告）日：2023-12-14

  本发明公开了一种化合物及其在制备BCL-XL抑制剂中的用途，属于制药领域。本发明提供的化合物结构如式I所示，该化合物可以有效结合BCL-XL蛋白，从而进一步抑制BCL-XL蛋白的活性。本发明化合物能够用于制备BCL-XL抑制剂，以及预防和/或治疗与BCL-XL蛋白活性有关疾病(例如癌症，自身免疫性疾病等)的药物，临床应用前景广阔。本发明化合物具有良好的药理学特性，其稳定性好、成药可能性高，并且该化合物制备方法简单，产率高，成本低，适合工业化生产。
• SUBSTITUTED PYRAZOLES AS PPAR AGONISTS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1685113B1

  公开（公告）日：2008-07-30
• [EN] SUBSTITUTED PYRAZOLES AS PPAR AGONISTS<br/>[FR] PYRAZOLES SUBSTITUES UTILISES EN TANT QU'AGONISTES DE PPAR
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005049578A1

  公开（公告）日：2005-06-02

  A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof (I) wherein: p is O or 1; q is O or 1; R1 and R2 are independently H or C1-3 alkyl; R3 and R4 are independently H, C1-6 alkyl, -OC1-6 alkyl, halogen, OH, C2-6 alkenyl or CF3; R5 is H, C1-6 alkyl (optionally substituted by one or more halogens, -COphenyl, OC1-6 alkyl, phenyl morpholino or C2-6 alkenyl. R6 is C1-6 alkyl, halogen, -OCH2 phenyl, phenyl (optionally substituted by C1-3 alkiyl), morpholino, pyrrolidino, piperidino, thiophenyl, furanyl pyridinyl or -OC2-6 alkenyl. These compounds activate the alpha and gamma subtypes fo the hppar receptor and are useful e.g. in the treatment of diabetes, dyslipidemia or syndrome X.

  式（I）的化合物及其药学上可接受的盐、溶剂化合物和可水解酯（I）其中：p为O或1；q为O或1；R1和R2独立地为H或C1-3烷基；R3和R4独立地为H、C1-6烷基、-OC1-6烷基、卤素、OH、C2-6烯基或CF3；R5为H、C1-6烷基（可选地被一个或多个卤素、-CO苯基、OC1-6烷基、苯基吗啡啉或C2-6烯基取代）。R6为C1-6烷基、卤素、-OCH2苯基、苯基（可选地被C1-3烷基取代）、吗啡啉、吡咯啉、哌啶、噻吩基、呋喃基吡啶基或-OC2-6烯基。这些化合物激活hppar受体的α和γ亚型，在糖尿病、血脂异常或X综合征的治疗中很有用。
• 5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII
  作者：Ilija N. Cvijetić、Muhammet Tanç、Ivan O. Juranić、Tatjana Ž. Verbić、Claudiu T. Supuran、Branko J. Drakulić

  DOI：10.1016/j.bmc.2015.05.052

  日期：2015.8

  Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4-50 mu M). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho-and meta-positions inhibited hCA IX with Kis ranging between 5 and 25 mu M. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.