2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester | 343321-95-9

• 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: 2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester
• 英文别名: 2-methyl-2-[4-{[(4-methyl-2-[4trifluoromethylphenyl]thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester；ethyl 2-methyl-2-[4-[[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carbonyl]amino]methyl]phenoxy]propanoate
• CAS: 343321-95-9
• 化学式: C₂₅H₂₅F₃N₂O₄S
• 分子量: 506.546
• InChiKey: QHOKKHFXFPZWNH-UHFFFAOYSA-N

物化性质

• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester 以75的产率得到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：

  Thiazole or oxazole derivatives which are useful in the treatment of cardiovascular and related diseases

  摘要：

  化合物的化学式为（I），其药学上可接受的盐、溶剂和可水解酯 其中 R1和R2独立地表示H或C1-3烷基，或者R1和R2与它们结合的碳原子一起形成3-5成员环烷基环； X1表示O或S； 每个R3、R4、R8和R9独立地表示H、卤素、—CH3和—OCH3； R5表示H或C1-6烷基，或者R4和R5一起形成3-6成员的环烷基环； X2表示NH、NCH3或O； Y和Z中的一个是N，另一个是O或S； R6表示苯基或吡啶基（其中N位于2或3位置），并且可以选择地被一个或多个卤素、CF3、C1-6直链或支链烷基（可选择地被卤素取代）取代，但当R6是吡啶基时，N未被取代； R7表示C1-6烷基（可选择地被一个或多个卤素取代）、—CO-8成员杂环烷基、C0-6烷基-(O)n-苯基，其中n为0或1，但当R1和R2为甲基、R8和R9为H、R5为H时，R7不能为CH3或CF3。

  公开号：

  US06867225B2
• 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 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 28.5h， 生成 2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]-1,3-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid ethyl ester
  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

• 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。
• Thiazole or oxazole derivatives which are useful in the treatment of cardiovascular and related diseases
  申请人：Dumaitre Bernard Andre

  公开号：US06867225B2

  公开（公告）日：2005-03-15

  A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof Wherein R 1 and R 2 are independently H or C 1-3 alkyl or R 1 and R 2 which are bonded to the same carbon atom may together with the carbon atom to which they are bonded form a 3-5 membered cycloalkyl ring; X 1 represents O or S; Each R 3 , R 4 , R 8 and R 9 independently represents H, halogen, —CH 3 and —OCH 3 ; R 5 represents H or C 1-6 alkyl or R 4 and R 5 together form a 3-6 membered cycloalkyl ring. X 2 represents NH, NCH 3 or O; One of Y and Z is N, and the other is O or S; R 6 represents phenyl or pyridyl (wherein the N is in position 2 or 3) and is optionally substituted by one or more halogen, CF 3 , C 1-6 straight or branched alkyl (optionally substituted by halogen), with the provision that when R 6 is pyridyl, the N is unsubstituted. R 7 represents C 1-6 alkyl, (optionally substituted by one or more halogens), —C 0-8 alkyl-5 membered heteroaryl, C 0-6 alkyl-(O) n -phenyl, wherein n is 0 or 1, with the proviso that when R 1 and R 2 are methyl, R 8 and R 9 are H, R 5 is H, then R 7 cannot be CH 3 or CF 3 .

  化合物的化学式为（I），其药学上可接受的盐、溶剂和可水解酯 其中 R1和R2独立地表示H或C1-3烷基，或者R1和R2与它们结合的碳原子一起形成3-5成员环烷基环； X1表示O或S； 每个R3、R4、R8和R9独立地表示H、卤素、—CH3和—OCH3； R5表示H或C1-6烷基，或者R4和R5一起形成3-6成员的环烷基环； X2表示NH、NCH3或O； Y和Z中的一个是N，另一个是O或S； R6表示苯基或吡啶基（其中N位于2或3位置），并且可以选择地被一个或多个卤素、CF3、C1-6直链或支链烷基（可选择地被卤素取代）取代，但当R6是吡啶基时，N未被取代； R7表示C1-6烷基（可选择地被一个或多个卤素取代）、—CO-8成员杂环烷基、C0-6烷基-(O)n-苯基，其中n为0或1，但当R1和R2为甲基、R8和R9为H、R5为H时，R7不能为CH3或CF3。
• [EN] SUBSTITUTED OXAZOLES AND THIAZOLES DERIVATIVES AS HPPAR ALPHA ACTIVATORS<br/>[FR] DERIVES D'OXAZOLES ET DE THIAZOLES SUBSTITUES EN TANT QU'ACTIVATEURS HPPAR (RECEPTEUR ACTIVE DE PROLIFERATION DU PERIXOSOME HUMAIN) ALPHA
  申请人：GLAXO GROUP LTD

  公开号：WO2001040207A1

  公开（公告）日：2001-06-07

  A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof wherein; X1 represents O or S; R?1 and R2¿ independently represent H, halogen, -CH¿3? and -OCH3; n represents 1 or 2; X2 represents NH, NCH3 or O; One of Y and Z is N, and the other is O or S; R?3¿ represents phenyl or pyridyl (wherein the N is in position 2 or 3) and is optionally substituted by one or more halogen, NO¿2?, NH2, CF3, OCF3, OC1-6 straight or branched alkyl, C1-6 straight or branched alkyl, alkenyl or alkynyl with the provision that when R?3¿ is pyridyl, the N is unsubstituted; R4 represents CF¿3? or CH3.

  化合物的公式（I）及其药学上可接受的盐、溶剂合物和可水解酯，其中：X1代表O或S；R?1和R2¿独立地代表H，卤素，-CH¿3?和-OCH3；n代表1或2；X2代表NH，NCH3或O；Y和Z中的一个是N，另一个是O或S；R?3¿代表苯基或吡啶基（其中N位于2或3位），并且可以被一个或多个卤素，NO¿2？ ，NH2，CF3，OCF3，OC1-6直链或支链烷基，C1-6直链或支链烷基，烯基或炔基取代，但当R?3¿为吡啶基时，N未被取代；R4代表CF¿3？或CH3。
• [EN] THIAZOLE OR OXAZOLE DERIVATIVES WHICH ARE USEFUL IN THE TREATMENT OF CARDIOVASCULAR AND RELATED DISEASES<br/>[FR] DERIVES DE THIAZOLE OU D'OXAZOLE POUVANT ETRE UTILISES DANS LE TRAITEMENT DES MALADIES CARDIOVASCULAIRES ET APPARENTEES
  申请人：GLAXO GROUP LTD

  公开号：WO2002096894A1

  公开（公告）日：2002-12-05

  A compound of formula (1) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof: wherein R?1 and R2¿ are independently H or C¿1-3? alkyl or R?1 and R2¿ which are bonded to the same carbon atom may together with the carbon atom to which they are bonded form a 3-5 membered cycloalkyl ring; X¿1? represents O or S; Each R?3, R4, R8 and R9¿ independently represents H, halogen, -CH¿3? and OCH3; R?5¿ represents H or C¿1-6? alkyl or R?4 and R5¿ together form a 3-6 membered cycloalkyl ring. X¿2? represents NH, NCH3 or O; One of Y and Z is N, and the other is O or S; R?6¿ represents phenyl or pyridyl (wherein the N is in position 2 or 3) and is optionally substituted by one more halogen, CF¿3?, C1-6 straight or branched alkyl (optionally substituted by halogen), with the provision that when R?6¿ is pyridyl, the N is unsubstituted. R7 represents C¿1-6? alkyl, (optionally substituted by one or halogens), -C0-6 alkyl-5 membered heteroaryl C0-6 alkyl (O)n- phenyl, wherein n is 0 or 1, with the proviso that when R?1 and R2¿ are methyl, R?8 and R9¿ are H, R5 is H, then R7 cannot be CH¿3? or CF3.

  化合物的式子（1）及其药学上可接受的盐、溶剂化合物和可水解酯：其中R1和R2分别为H或C1-3烷基，或者R1和R2结合到同一个碳原子上，可以与它们结合的碳原子一起形成3-5成员的环烷基环；X1表示O或S；每个R3、R4、R8和R9分别表示H、卤素、-CH3和OCH3；R5表示H或C1-6烷基，或者R4和R5一起形成3-6成员的环烷基环。X2表示NH、NCH3或O；Y和Z中的一个是N，另一个是O或S；R6表示苯基或吡啶基（其中N在2或3位置），并且可以选择性地被一个或多个卤素、CF3、C1-6直链或支链烷基（可选择性地被卤素取代）取代，但是当R6是吡啶基时，N没有被取代。R7表示C1-6烷基（可选择性地被一个或多个卤素取代）、-C0-6烷基-5成员杂环烷基C0-6烷基（O）n-苯基，其中n为0或1，但是当R1和R2为甲基，R8和R9为H，R5为H时，R7不能是CH3或CF3。
• Furan and thiophene derivatives that activate human peroxisome profilerator activated receptors
  申请人：——

  公开号：US20040157890A1

  公开（公告）日：2004-08-12

  A compound of formula (I) or pharmaceutically acceptable salts and solvates thereof, for the treatment of a hPPAR mediated disease or condition. 1

  化合物公式（I）或其药学上可接受的盐和溶剂，用于治疗hPPAR介导的疾病或病况。