methyl 2-[3,5-dichloro-4-[4-methoxy-3-[4-(trifluoromethyl)phenyl]phenoxy]phenyl]acetate | 788824-24-8

• 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: methyl 2-[3,5-dichloro-4-[4-methoxy-3-[4-(trifluoromethyl)phenyl]phenoxy]phenyl]acetate
• CAS: 788824-24-8
• 化学式: C₂₃H₁₇Cl₂F₃O₄
• 分子量: 485.287
• InChiKey: SMGHOCTXNFYGOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 2-[3,5-dichloro-4-[4-methoxy-3-[4-(trifluoromethyl)phenyl]phenoxy]phenyl]acetate 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 [3,5-Dichloro-4-(6-hydroxy-4'-trifluoromethyl-biphenyl-3-yloxy)-phenyl]-acetic acid methyl ester
  参考文献：
  名称：

  Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta

  摘要：

  A set of thyromimetics having improved selectivity for TR-beta1 were prepared by replacing the 3'-isopropyl group of 2 and 3 with substituents having increased steric bulk. From this limited SAR study, the most potent and selective compounds identified were derived from 2 and contained a 3'-phenyl moiety bearing small hydrophobic groups meta to the biphenyl link. X-ray crystal data of 15c complexed with TR-beta1 LBD shows methionine 442 to be displaced by the bulky R3' phenyl ethyl amide side chain. Movement of this amino acid side chain provides an expanded pocket for the bulky side chain while the ligand-receptor complex retains full agonist activity.

  DOI：

  10.1016/j.bmcl.2004.04.032
• 作为产物：
  描述：

  [4-(3-Bromo-4-methoxy-phenoxy)-3,5-dichloro-phenyl]-acetic acid methyl ester 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 potassium acetate 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 二甲基亚砜 为溶剂， 生成 methyl 2-[3,5-dichloro-4-[4-methoxy-3-[4-(trifluoromethyl)phenyl]phenoxy]phenyl]acetate
  参考文献：
  名称：

  Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta

  摘要：

  A set of thyromimetics having improved selectivity for TR-beta1 were prepared by replacing the 3'-isopropyl group of 2 and 3 with substituents having increased steric bulk. From this limited SAR study, the most potent and selective compounds identified were derived from 2 and contained a 3'-phenyl moiety bearing small hydrophobic groups meta to the biphenyl link. X-ray crystal data of 15c complexed with TR-beta1 LBD shows methionine 442 to be displaced by the bulky R3' phenyl ethyl amide side chain. Movement of this amino acid side chain provides an expanded pocket for the bulky side chain while the ligand-receptor complex retains full agonist activity.

  DOI：

  10.1016/j.bmcl.2004.04.032

文献信息

• THYROID RECEPTOR LIGANDS
  申请人：Ryono Denis E.

  公开号：US20100298276A1

  公开（公告）日：2010-11-25

  Thyroid receptor ligands are provided which have the general formula I wherein: R 1 is R 2 and R 3 are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, provided that at least one of R 2 and R 3 is other than hydrogen; R 4 is R 5 and R 6 are the same or different and are selected from hydrogen, aryl, heteroaryl, alkyl, cycloalkyl, aralkyl or heteroaralkyl. R 7 is aryl, heteroaryl, alkyl, aralkyl, or heteroaralkyl; R 8 is aryl, heteroaryl, or cycloalkyl; R 9 is R 7 or hydrogen; R 10 is hydrogen, halogen, cyano or alkyl; R 11 and R 12 are each independently selected from the group consisting of hydrogen, halogen, alkoxy, hydroxy (—OH) cyano, and alkyl; R 13 is carboxylic acid (COOH) or esters thereof, phosphonic and phosphinic acid or esters thereof, sulfonic acid, tetrazole, hydroxamic acid, thiazolidinedione, acylsulfonamide, or other carboxylic acid surrogates known in the art; R 14 and R 15 may be the same or different and are selected from hydrogen and alkyl, or R 14 and R 15 may be joined together forming a chain of 2 to 5 methylene groups [—(CH2)m-, m=2, 3, 4 or 5], thus forming 3- to 6-membered cycloalkyl rings; R 16 is hydrogen or alkyl of 1 to 4 carbons; R 17 and R 18 are the same or different and selected from hydrogen, halogen and alkyl; n is 0 or an integer from 1 to 4; X is oxygen (—O—), sulfur (—S—), sulfonyl (—SO 2 —), sulfenyl (—SO—) selenium (—Se—), carbonyl (—CO—), amino (—NH—) or methylene (—CH2-); wherein the substituents are as described herein. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T 3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount.

  提供了甲状腺受体配体，其具有一般公式I，其中：R1为R2和R3，R2和R3相同或不同，为氢、卤素、1至4个碳原子的烷基或3至5个碳原子的环烷基，但至少其中一个为非氢；R4为R5和R6，R5和R6相同或不同，选择自氢、芳基、杂环芳基、烷基、环烷基、芳基烷基或杂环芳基；R7为芳基、杂环芳基、烷基、芳基烷基或杂环芳基；R8为芳基、杂环芳基或环烷基；R9为R7或氢；R10为氢、卤素、氰基或烷基；R11和R12各自独立选择自氢、卤素、烷氧基、羟基（—OH）、氰基和烷基；R13为羧酸（COOH）或其酯、膦酸和膦酸酯、磺酸、四唑、羟胺酸、噻唑二酮、酰基磺胺或艺术中已知的其他羧酸替代物；R14和R15可相同或不同，选择自氢和烷基，或R14和R15可结合形成2至5个亚甲基组成的链[—(CH2)m-，m=2、3、4或5]，从而形成3至6成员的环烷基环；R16为氢或1至4个碳原子的烷基；R17和R18相同或不同，选择自氢、卤素和烷基；n为0或1至4的整数；X为氧（—O—）、硫（—S—）、砜基（—SO2—）、砜基（—SO—）、硒（—Se—）、羰基（—CO—）、氨基（—NH—）或亚甲基（— -）；其中取代基如上述所述。此外，提供了一种方法，用于预防、抑制或治疗与代谢功能障碍或依赖于T3调节基因表达的疾病或障碍，其中上述化合物以治疗有效剂量给予。