2-甲基-2-[4-[[4-甲基-2-[4-（三氟甲基）苯基]噻唑-5-羧酰胺基]甲基]苯氧基]丙酸 | 343321-96-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-甲基-2-[4-[[4-甲基-2-[4-（三氟甲基）苯基]噻唑-5-羧酰胺基]甲基]苯氧基]丙酸
• 英文名称: GW590735
• 英文别名: 2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]-thiazol-5-ylcarbonyl)amino]methyl}-phenoxy]propionic acid；2-Methyl-2-(4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazole-5-carboxamido)methyl)phenoxy)propanoic acid；2-methyl-2-[4-[[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carbonyl]amino]methyl]phenoxy]propanoic acid
• CAS: 343321-96-0；622402-22-6
• 化学式: C₂₃H₂₁F₃N₂O₄S
• 分子量: 478.492
• InChiKey: ILUPZUOBHCUBKB-UHFFFAOYSA-N

物化性质

• 熔点：
  130-131 °C(Solv: toluene (108-88-3))
• 密度：
  1.342±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(三氟甲基)硫代苯甲酰胺 在 sodium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 46.5h， 生成 2-甲基-2-[4-[[4-甲基-2-[4-（三氟甲基）苯基]噻唑-5-羧酰胺基]甲基]苯氧基]丙酸
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x

文献信息

• Thia-and oxazoles and their use as ppars activators
  申请人：——

  公开号：US20040102493A1

  公开（公告）日：2004-05-27

  A compound of formula (I) or pharmaceutically acceptable salts and solvates thereof. R 1 and R 2 are independently H or C 1-3 alkyl, m is 0-3; X 1 is NH, NCH 3 , O, S; R 3 , R 4 and R 5 are independently H, CH 3 , CF 3 , OCH 3 , allyl or halogen; X 2 is (CR 10 R 11 )n wherein n is 1 or 2; R 10 and R 11 independently represent H, fluorine or C 1-16 alkyl; R 26 and R 27 are independently H, C 1-3 alkyl or R 26 and R 27 together with the carbon atom to which they are bonded form a 3-5 membered cycloalklyl ring. R 6 and R 7 independently represent H, fluorine or C 1-16 alkyl; R 9 is C 1-6 alkyl or CF 3 ; One of Y and Z is N, the other is S or O; Each R 8 independently represents CF 3 , OCH 3 , CH 3 or halogen; y is O, 1, 2, 3, 4, 5. Use of a compound of formula (I) for the manufacture of a medicament for the prevention or treatment of a hPPAR mediated disease or condition, such as dyslipidemia, syndrome X, heart failure, hypercholesteremia, cardiovascular disease, type II diabetes mellitus, type 1 diabetes, insulin resistance hyperlipidemia, obesity, anorexia bulimia, inflammation and anorexia nervosa. 1

  一种具有化学式（I）或其药学上可接受的盐和溶剂的化合物。R1和R2独立地表示H或C1-3烷基，m为0-3；X1为NH、NCH3、O、S；R3、R4和R5独立地表示H、CH3、CF3、OCH3、烯丙基或卤素；X2为（CR10R11）n，其中n为1或2；R10和R11独立地表示H、氟或C1-16烷基；R26和R27独立地表示H、C1-3烷基或R26和R27与它们结合的碳原子一起形成3-5环的环烷基环。R6和R7独立地表示H、氟或C1-16烷基；R9为C1-6烷基或CF3；Y和Z中的一个为N，另一个为S或O；每个R8独立地表示CF3、OCH3、CH3或卤素；y为O、1、2、3、4、5。使用具有化学式（I）的化合物制备用于预防或治疗hPPAR介导的疾病或症状的药物，例如脂质代谢异常、X综合征、心力衰竭、高胆固醇血症、心血管疾病、2型糖尿病、1型糖尿病、胰岛素抵抗性高脂血症、肥胖、厌食症、炎症和神经性厌食症。
• [EN] PHENYLALKANOIC ACID AND PHENYLOXYALKANOIC ACID DERIVATIVES AS HPPAR ACTIVATORS<br/>[FR] ACIDE PHENYLALKANOIQUE ET DERIVES D'ACIDE PHENYLOXYALKANOIQUE EN TANT QU'ACTIVATEURS DE HPPAR
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004000315A1

  公开（公告）日：2003-12-31

  The present invention provides a compound of formula (I):wherein:R1 and R2 are independently H or C1-3 alkyl;X represents a O or (CH2)n where n is 0, 1 or 2;R3and R4 independently represent H, C1-3 alkyl, -OCH3, -CF3, allyl, or halogen;X1 represents O, S, SO2, SO, or CH2;R5 and R6 independently represent hydrogen, C1-6 alkyl (including branched alkyl and optionally substituted by one or more halogens or C1-6alkoxy), or together with the carbon atom to which they are bonded form a 3-6 membered cycloalkyl ring;R7 represents a phenyl or a 6 membered heteroaryl group containing 1, 2 or 3 nitrogen atoms wherein the phenyl or heteroaryl group is substituted by 1, 2 or 3 moieties selected from the group consisting of halogen, C1-6 alkoxy, C1-6 alkyl, CF3, hydroxy, or phenyl (which may be optionally substituted by one or more C1-3 alkyl, -OC1-3 alkyl, CN, acetyl, hydroxy, halogen or CF3).

  本发明提供了一种具有以下结构的化合物(I)：其中：R1和R2分别独立地表示H或C1-3烷基；X代表O或(CH2)n，其中n为0、1或2；R3和R4独立地表示H、C1-3烷基、-OCH3、-CF3、烯丙基或卤素；X1代表O、S、SO2、SO或CH2；R5和R6独立地表示氢、C1-6烷基（包括支链烷基，并且可以选择性地被一个或多个卤素或C1-6烷氧基取代），或者与它们键合的碳原子一起形成一个3-6环状烷基环；R7表示苯基或含有1、2或3个氮原子的6元杂芳基，其中苯基或杂芳基被选自卤素、C1-6烷氧基、C1-6烷基、CF3、羟基或苯基（可以选择性地被一个或多个C1-3烷基、-OC1-3烷基、CN、乙酰基、羟基、卤素或CF3取代）的1、2或3个取代基取代。
• Thiazole derivatives for treating ppar related disorders
  申请人：——

  公开号：US20040063964A1

  公开（公告）日：2004-04-01

  The present invention provides compounds of formula (I). These compounds are used for the treatment of PPAR related diseases. 1

  本发明提供了式(I)的化合物。这些化合物用于治疗与PPAR相关的疾病。
• Substituted oxazoles and thiazoles as hppar alpha agonists
  申请人：——

  公开号：US20040147571A1

  公开（公告）日：2004-07-29

  Compounds of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof wherein X is O or S; X 1 is O or S; X is S or O; R 1 and R 2 are independently H, methyl, or halogen; R 4 and R 5 are independently H or C 1-3 alkyl or R 4 and R 5 may, together with the carbon atom to which they are bonded, form a 3-5 membered cycloalkyl ring; R 6 and R 7 are independently H, C 1-3 alkyl, or allyl; each R 3 is independently halogen, C 1-6 straight or branched alkyl, or CF 3 ; and y is 0, 1, 2, 3, 4 or 5 act as hPPAR alpha agonists.

  化合物的式（I）及其药学上可接受的盐，溶剂化物和可水解酯，其中X为O或S；X1为O或S；X为S或O；R1和R2独立地为H、甲基或卤素；R4和R5独立地为H或C1-3烷基或R4和R5可以与它们所连接的碳原子一起形成3-5成员的环烷基环；R6和R7独立地为H、C1-3烷基或烯丙基；每个R3独立地为卤素、C1-6直链或支链烷基或CF3；y为0、1、2、3、4或5，可以作为hPPAR alpha激动剂。
• [EN] THIAZOLE DERIVATIVES FOR TREATING PPAR RELATED DISORDERS<br/>[FR] DERIVES THIAZOLE DESTINES AU TRAITEMENT DE TROUBLES ASSOCIES A DES RECEPTEURS PPAR
  申请人：GLAXO GROUP LTD

  公开号：WO2002062774A1

  公开（公告）日：2002-08-15

  The present invention provides compounds of formula (I). These compounds are used for the treatment of PPAR related diseases.

  本发明提供了式(I)的化合物。这些化合物用于治疗与PPAR相关的疾病。