[(4-{3-[(4-氟苯基)(羟基)甲基]-4-羟基苯氧基}-3,5-二甲基苯基)氨基](羰基)乙酸 | 169799-03-5

• 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: [(4-{3-[(4-氟苯基)(羟基)甲基]-4-羟基苯氧基}-3,5-二甲基苯基)氨基](羰基)乙酸
• 英文名称: N-<4-<3-<(4-fluorophenyl)hydroxymethyl>-4-hydroxyphenoxy>-3,5-dimethylphenyl>oxamic acid
• 英文别名: N-[4-[3'-[(4-fluorophenyl) hydroxymethyl]-4'-hydroxyphenoxy]-3,5dimethylphenyl]oxamic acid；((4-(3-(4-Fluoro-alpha-hydroxybenzyl)-4-hydroxyphenoxy)-3,5-dimethylphenyl)amino)oxoacetate；2-[4-[3-[(4-fluorophenyl)-hydroxymethyl]-4-hydroxyphenoxy]-3,5-dimethylanilino]-2-oxoacetic acid
• CAS: 169799-03-5
• 化学式: C₂₃H₂₀FNO₆
• 分子量: 425.413
• InChiKey: JLRFZRFZFZGWFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-[4-[3'-(4-fluorobenzoyl)4'-hydroxyphenoxy]-3,5-dimethylphenyl]oxamic acid 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以9.5%的产率得到[(4-{3-[(4-氟苯基)(羟基)甲基]-4-羟基苯氧基}-3,5-二甲基苯基)氨基](羰基)乙酸
  参考文献：
  名称：

  与L-甲状腺素有关的草酸和乙酸衍生物的合成及其构效关系。

  摘要：

  制备了与L-三碘甲甲状腺素（L-T3）有关的芳基草酸7和23，（芳基氨基）乙酸29，芳基丙酸33，芳基硫代乙酸37和（芳氧基）乙酸41并在体外测试了与大鼠肝脏的结合核L-T3受体和大鼠膜L-T3受体。描述了这些化合物的构效关系，其中7f，23a，29c，33a，37b和41对核受体显示出出色的效价（IC50分别为0.19、0.16、1.1、0.11、3.5和0.10 nM）。并显着降低了对膜受体的结合亲和力（IC50> 5 microM）。这些化合物中的某些，尤其是草酰胺酸系列7和23，对甲基取代的衍生物（例如7f和23a）表现出空前的效价。化合物7f和23a在具有ED50'的大鼠中显示出良好的降脂作用

  DOI：

  10.1021/jm00004a015

文献信息

• Heteroacetic acid derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05401772A1

  公开（公告）日：1995-03-28

  Disclosed are compounds of formula ##STR1## wherein R is hydroxy, esterified hydroxy or etherified hydroxy; R.sub.1 is halogen, trifluoromethyl or lower alkyl; R.sub.2 is halogen, trifluoromethyl or lower alkyl; R.sub.3 is halogen, trifluoromethyl, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl; or R.sub.3 is the radical ##STR2## wherein R.sub.8 is hydrogen, lower alkyl, aryl, cycloalkyl, aryl-lower alkyl or cycloalkyl-lower alkyl; R.sub.9 is hydroxy or acyloxy; R.sub.10 represents hydrogen or lower alkyl; or R.sub.9 and R.sub.10 together represent oxo; R.sub.4 is hydrogen, halogen, trifluoromethyl or lower alkyl; X is --NR.sub.7, S or O; W is O or S; R.sub.5 represents hydrogen, lower alkyl or aryl-lower alkyl;and R.sub.6 represents hydrogen; or R.sub.5 and R.sub.6 together represent oxo provided that X represents --NR.sub.7; R.sub.7 represents hydrogen or lower alkyl; Z represents carboxyl, carboxyl derivatized as a pharmaceutically acceptable ester or as a pharmaceutically acceptable amide; and pharmaceutically acceptable salts thereof; which are useful as hypocholesteremic agents.

  揭示了以下式的化合物##STR1##其中R是羟基，酯化羟基或醚化羟基；R.sub.1是卤素，三氟甲基或较低烷基；R.sub.2是卤素，三氟甲基或较低烷基；R.sub.3是卤素，三氟甲基，较低烷基，芳基，芳基-较低烷基，环烷基或环烷基-较低烷基；或R.sub.3是基团##STR2##其中R.sub.8是氢，较低烷基，芳基，环烷基，芳基-较低烷基或环烷基-较低烷基；R.sub.9是羟基或酰氧基；R.sub.10代表氢或较低烷基；或R.sub.9和R.sub.10一起代表氧代；R.sub.4是氢，卤素，三氟甲基或较低烷基；X是--NR.sub.7，S或O；W是O或S；R.sub.5代表氢，较低烷基或芳基-较低烷基；和R.sub.6代表氢；或R.sub.5和R.sub.6一起代表氧代，前提是X代表--NR.sub.7；R.sub.7代表氢或较低烷基；Z代表羧基，羧基衍生物，作为药学上可接受的酯或作为药学上可接受的酰胺；及其药学上可接受的盐；这些化合物可用作降胆固醇药物。
• Oxamic acid derivatives as hypocholesteremic agents
  申请人：CIBA-GEIGY AG

  公开号：EP0580550A1

  公开（公告）日：1994-01-26

  Disclosed are compounds of formula wherein    R is hydrogen, hydroxy, esterified hydroxy or etherified hydroxy;    R₁ is hydrogen, halogen, trifluoromethyl or lower alkyl;    R₂ is hydrogen, halogen, trifluoromethyl or lower alkyl;    R₃ is halogen, trifluoromethyl, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl; or    R₃ is the radical wherein R₈ is hydrogen, lower alkyl, aryl, cycloalkyl, aryl-lower alkyl or cycloalkyl-lower alkyl; R₉ is hydroxy or acyloxy; R₁₀ represents hydrogen or lower alkyl; or R₉ and R₁₀ together represent oxo;    R₄ is hydrogen, halogen, trifluoromethyl or lower alkyl;    X is -NR₇;    W is O or S;    R₅ and R₆ together represent oxo;    R₇ represents hydrogen or lower alkyl;    Z represents carboxyl, carboxyl derivatized as a pharmaceutically acceptable ester or as a pharmaceutically acceptable amide; and pharmaceutically acceptable salts thereof; which are useful as hypocholesteremic agents.

  所公开的是式 其中 R 是氢、羟基、酯化羟基或醚化羟基； R₁ 是氢、卤素、三氟甲基或低级烷基； R₂ 是氢、卤素、三氟甲基或低级烷基； R₃ 是卤素、三氟甲基、低级烷基、芳基、芳基-低级烷基、环烷基或环烷基-低级烷基；或 R₃ 是基团 其中 R₈ 是氢、低级烷基、芳基、环烷基、芳基-低级烷基或环烷基-低级烷基；R₉ 是羟基或酰氧基；R₁₀ 代表氢或低级烷基；或 R₉ 和 R₁₀ 共同代表氧代； R₄ 是氢、卤素、三氟甲基或低级烷基； X 是-NR₇； W 是 O 或 S； R₅ 和 R₆ 共同代表氧代； R₇ 代表氢或低级烷基； Z 代表羧基、作为药学上可接受的酯或作为药学上可接受的酰胺的羧基衍生物；及其药学上可接受的盐；可用作降胆固醇药。
• Thyromimetic antiobesity agents
  申请人：Pfizer Products Inc.

  公开号：EP1036564A1

  公开（公告）日：2000-09-20

  The invention relates to pharmaceutical compositions and methods useful in the treatment of obesity which methods comprise administering to animal, including a human or companion animal, in need of such treatment an effective amount of a compound of the structural formula or a pharmaceutically acceptable salt, racemate or enantiomer thereof, wherein R is hydroxy, esterified hydroxy or etherified hydroxy; R1 and R2 are, independently, halogen, trifluoromethyl or lower alkyl; R3 is halogen, trifluoromethyl, lower alkyl, aryl, aryl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl, carbocyclic arylmethyl, carbocyclic aroyl, carbocyclic arylhydroxymethyl; or R3 is the radical wherein R8 is hydrogen, lower alkyl, aryl, cycloalkyl, aryl-lower alkyl or cycloalkyl-lower alkyl; R9 is hydroxy or acyloxy; R10 is hydrogen or lower alkyl; or R9 and R10, taken together with the carbon atom to which they are attached, form a carbonyl group; R4 is hydrogen, halogen, trifluoromethyl or lower alkyl; R5 and R6 are, independently, hydrogen or lower alkyl or R5 and R6, taken together with the carbon atom to which they are attached, form a carbonyl group; X is O, S or -NR7; R7 is hydrogen or lower alkyl; W is O or S; and Z is carboxyl or carboxyl derivatized as a pharmaceutically acceptable ester or amide. The invention further provides for pharmaceutical compositions and methods of using the compounds of structural formula (I), or the pharmaceutically acceptable salts, racemates and enantiomers thereof, in combination with an anorectic agent, in treating obesity.

  本发明涉及用于治疗肥胖症的药物组合物和方法，其方法包括向需要治疗的动物（包括人或伴侣动物）施用有效量的结构式如下的化合物 或其药学上可接受的盐、外消旋体或对映体，其中 R 是羟基、酯化羟基或醚化羟基； R1 和 R2 分别为卤素、三氟甲基或低级烷基； R3 是卤素、三氟甲基、低级烷基、芳基、芳基-低级烷基、环烷基或环烷基-低 级烷基、碳环芳基甲基、碳环芳基、碳环芳基羟甲基；或 R3 是基团 其中 R8 是氢、低级烷基、芳基、环烷基、芳基-低级烷基或环烷基-低级烷基； R9 是羟基或酰氧基；R10 是氢或低级烷基；或 R9 和 R10 与它们所连接的碳原子一起形成一个羰基； R4 是氢、卤素、三氟甲基或低级烷基； R5 和 R6 分别为氢或低级烷基，或 R5 和 R6 与它们所连接的碳原子一起形成一个羰基； X 是 O、S 或-NR7； R7 是氢或低级烷基 W 是 O 或 S；以及 Z 是羧基或羧基衍生化的药学上可接受的酯或酰胺。 本发明进一步提供了使用结构式（I）化合物或其药学上可接受的盐、外消旋体和对映体的药物组合物和方法，结合一种厌食症药物治疗肥胖症。
• Anti-hypercholesterolemic drug combination
  申请人：——

  公开号：US20030212137A1

  公开（公告）日：2003-11-13

  This invention provides a drug combination comprised of a thyroid hormone receptor beta agonist with a fibrate in therapeutically effective amounts, which is useful for reducing cholesterol synthesis, lowering plasma cholesterol levels and lowering plasma triglyceride levels.

  本发明提供了一种由甲状腺激素受体β激动剂和治疗有效量的纤维酸盐组成的药物组合，可用于减少胆固醇合成、降低血浆胆固醇水平和血浆甘油三酯水平。
• Method for stimulating weight loss and/or for lowering triglycerides in patients
  申请人：Morkin Eugene

  公开号：US20080146668A1

  公开（公告）日：2008-06-19

  Administration of a therapeutically effective amount of 3,5-diiodothyropropionic acid stimulates weight loss in patients, lowers triglyceride levels and reduces risk of death or progression of coronary heart disease in patients with metabolic syndrome.