2-[(4-{[({5-[4-(1,1-dimethylethyl)phenyl]-1-methyl-1H-pyrazol-3-yl}carbonyl)amino]methyl}-2-methylphenyl)oxy]-2-methylpropanoic acid | 852814-21-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-[(4-{[({5-[4-(1,1-dimethylethyl)phenyl]-1-methyl-1H-pyrazol-3-yl}carbonyl)amino]methyl}-2-methylphenyl)oxy]-2-methylpropanoic acid
• 英文别名: GSK183390A；Propanoic acid, 2-(4-((((5-(4-(1,1-dimethylethyl)phenyl)-1-methyl-1H-pyrazol-3-yl)carbonyl)amino)methyl)-2-methylphenoxy)-2-methyl-；2-[4-[[[5-(4-tert-butylphenyl)-1-methylpyrazole-3-carbonyl]amino]methyl]-2-methylphenoxy]-2-methylpropanoic acid
• CAS: 852814-21-2
• 化学式: C₂₇H₃₃N₃O₄
• 分子量: 463.577
• InChiKey: BMCXRYMMKLEOTJ-UHFFFAOYSA-N

物化性质

• 熔点：
  136-137 °C(Solv: isopropyl acetate (108-21-4))
• 沸点：
  651.3±55.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  93.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ((1-(4-(tert-butyl)phenyl)vinyl)oxy)trimethylsilane 在 氯化亚砜 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 4.45h， 生成 2-[(4-{[({5-[4-(1,1-dimethylethyl)phenyl]-1-methyl-1H-pyrazol-3-yl}carbonyl)amino]methyl}-2-methylphenyl)oxy]-2-methylpropanoic acid
  参考文献：
  名称：

  Development of a Scalable Synthesis of GSK183390A, a PPAR α/γ Agonist

  摘要：

  A scalable synthesis of GSK183390A, a PPAR alpha/gamma agonist, is described. This synthesis is highlighted by (1) a regioselective formal 1,3-dipolar cycloaddition reaction between an enamine and a nitrile imine dipole to form a 1,3,5-trisubstituted pyrazole and (2) a regioselective amidomethylation of an o-cresol derivative using 2-chloro-N-hydroxymethylacetamide.

  DOI：

  10.1021/op700164t

文献信息

• [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。
• 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。
• The discovery of equipotent PPARα/γ dual activators
  作者：Paul Martres、Nicolas Faucher、Alain Laroze、Olivier Pineau、Marie Helene Fouchet、Florent Potvain、Didier Grillot、Veronique Beneton

  DOI：10.1016/j.bmcl.2008.09.094

  日期：2008.12

  We report the design and synthesis of equipotent PPAR alpha/gamma dual agonists starting from selective PPAR alpha agonist 1. In vivo data for 7 in the Zucker fa/fa rat are presented. (C) 2008 Elsevier Ltd. All rights reserved.
• SUBSTITUTED PYRAZOLES AS PPAR AGONISTS
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：EP1685113A1

  公开（公告）日：2006-08-02
• SYSTEMS AND METHODS FOR ENHANCING VACCINE EFFICACY
  申请人：Phipps Richard P.

  公开号：US20110300129A1

  公开（公告）日：2011-12-08

  Pharmaceutical compositions of the invention include an antigen or a nucleic acid molecule encoding the antigen; one or both of a PPAR ligand and an RxR ligand; and a pharmaceutically suitable carrier. The pharmaceutical composition can optionally include a mitogen or other additives. Also disclosed are methods of inducing B cell differentiation and promoting an immune response against an antigen.