3,5-dibromo-4-(4'-methoxy-3'-isopropyl-phenoxy)benzoic acid | 219692-12-3

• 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: 3,5-dibromo-4-(4'-methoxy-3'-isopropyl-phenoxy)benzoic acid
• 英文别名: 3,5-dibromo-4-(3-isopropyl-4-methoxyphenoxy)benzoate；3,5-Dibromo-4-(4-methoxy-3-isopropylphenoxy)benzoic acid；3,5-dibromo-4-(4-methoxy-3-propan-2-ylphenoxy)benzoic acid
• CAS: 219692-12-3
• 化学式: C₁₇H₁₆Br₂O₄
• 分子量: 444.12
• InChiKey: YAVNTSCGUSQEKV-UHFFFAOYSA-N

物化性质

• 沸点：
  472.433±45.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.592±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,5-dibromo-4-(4'-methoxy-3'-isopropyl-phenoxy)benzoic acid 、 4-硝基苯磺酰胺 以gave 8 mg (37%) of the title compound的产率得到3,5-Dibromo-4-(4-hydroxy-3-isopropylphenoxy)benzoyl-4-nitrobenzenesulphonamide
  参考文献：
  名称：

  Thyroid receptor ligands and method II

  摘要：

  提供了通式（I）的新甲状腺受体配体，其中：n是0到4的整数；R1是卤素，三氟甲基，或1到6个碳的烷基或3到7个碳的环烷基；R2和R3相同或不同，是氢，卤素，1到4个碳的烷基或3到5个碳的环烷基，其中至少一个R2和R3不是氢；R4是羧酸酰胺（CONR′R″）或酰基磺酰胺（CONHSO2R′）衍生物，或其药学上可接受的盐，以及其所有立体异构体；或当n等于或大于1时，R4可以是取代或未取代的杂环芳香族基，或胺（NR′R″）。R5是氢或酰基（例如乙酰或苯甲酰）或其他可生物转化为生成自由酚结构的基团（其中R5 = H）。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调节基因表达有关的疾病，在其中以上述化合物以治疗有效量进行治疗。这些与代谢功能障碍或依赖于T3调节基因表达有关的疾病的例子包括肥胖症，高胆固醇血症，动脉硬化，心律失常，抑郁症，骨质疏松症，甲状腺功能减退症，甲状腺肿，甲状腺癌以及青光眼，充血性心力衰竭和皮肤疾病。

  公开号：

  US06989402B1

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。
• Novel thyroid receptor ligands and method II
  申请人：Hangeland Jon

  公开号：US20050282872A1

  公开（公告）日：2005-12-22

  New thyroid receptor ligands are provided which have general formula (I) in which: n is an integer from 0 to 4; R 1 is halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; R 2 and R 3 are the same or differential hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, at least one of R 2 and R 3 being other than hydrogen; R 4 is a carboxylic acid thereof; or when n is equal to or greater than one, R 4 may be heteroaromatic moiety which may be substituted or unsubstituted, or an amine (NR′R″). R 5 is hydrogen or an acyl (such as acetyl or benzoyl) or other group capable of bioconversion to generate the free phenol structure (wherein R 5 —H). In addition, a method is provided for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependant upon the expression of a T 3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount. Examples of such diseases associated with metabolism dysfunction or are dependent upon the expression of a T 3 regulated gene include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma, congestive heart failure and skin disorders.

  提供了新的甲状腺受体配体，其具有以下通式（I）：其中：n是从0到4的整数；R1是卤素、三氟甲基或1至6个碳原子的烷基或3至7个碳原子的环烷基；R2和R3相同或不同，是氢、卤素、1至4个碳原子的烷基或3至5个碳原子的环烷基，其中至少有一个是氢之外的其他基团；R4是其羧酸；或当n等于或大于1时，R4可以是杂环芳基团，可能被取代或未取代，或胺（NR′R″）。R5是氢或酰基（如乙酰基或苯甲酰基）或其他能够生物转化以生成游离酚结构（其中R5-H）的基团。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相关或依赖于T3调节基因表达的疾病，其中上述描述的化合物以治疗有效剂量给予。与代谢功能障碍相关或依赖于T3调节基因表达的疾病的例子包括肥胖症、高胆固醇血症、动脉粥样硬化、心律失常、抑郁症、骨质疏松症、甲状腺功能减退症、甲状腺肿、甲状腺癌以及青光眼、充血性心力衰竭和皮肤疾病。
• Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders
  申请人：Malm Johan

  公开号：US20050107347A1

  公开（公告）日：2005-05-19

  This invention relates to novel compounds which are thyroid receptor ligands, preferably antagonists, and to methods for using such compounds in the treatment of cardiac and metabolic disorders, such as cardiac arrhythmias, thyrotoxicosis, subclinical hyperthyrodism and liver diseases.

  本发明涉及一种新型化合物，其是甲状腺受体配体，优选为拮抗剂，并涉及使用此类化合物治疗心脏和代谢性疾病的方法，例如心律失常、甲状腺毒症、亚临床甲状腺功能亢进和肝脏疾病。
• Thyroid receptor ligands
  申请人：Ryono E. Denis

  公开号：US20050004184A1

  公开（公告）日：2005-01-06

  Thyroid receptor ligands are provided which have the general formula I wherein: R1 is R2 and R3 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 R2 and R3 is other than hydrogen; R4 is R5 and R6 are the same or different and are selected from hydrogen, aryl, heteroaryl, alkyl, cycloalkyl, aralkyl or heteroaralkyl. R7 is aryl, heteroaryl, alkyl, aralkyl, or heteroaralkyl; R8 is aryl, heteroaryl, or cycloalkyl; R9 is R7 or hydrogen; R10 is hydrogen, halogen, cyano or alkyl; R11 and R12 are each independently selected from the group consisting of hydrogen, halogen, alkoxy, hydroxy (—OH) cyano, and alkyl; R13 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; R14 and R15 may be the same or different and are selected from hydrogen and alkyl, or R14 and R15 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; R16 is hydrogen or alkyl of 1 to 4 carbons; R17 and R18 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.

  所提供的甲状腺受体配体具有通式 I 其中 R1 是 R2和R3相同或不同，并且是氢、卤素、1至4个碳原子的烷基或3至5个碳原子的环烷基，条件是R2和R3中至少有一个不是氢； R4 是 R5 和 R6 相同或不同，选自氢、芳基、杂芳基、烷基、环烷基、芳基或杂烷基。R7 是芳基、杂芳基、烷基、芳烷基或杂烷基；R8 是芳基、杂芳基或环烷基；R9 是 R7 或氢；R10 是氢、卤素、氰基或烷基；R11 和 R12 各自独立地选自氢、卤素、烷氧基、羟基（-OH）氰基和烷基组成的组；R13 是羧酸（COOH）或其酯、膦酸和膦酸或其酯、磺酸、四唑、羟肟酸、噻唑烷二酮、酰基磺酰胺或本领域已知的其他羧酸代用品；R14 和 R15 可以相同或不同，并且选自氢和烷基，或者 R14 和 R15 可以连接在一起，形成 2 至 5 个亚甲基[-(CH2)m-，m=2、3、4 或 5]链，从而形成 3 至 6 元环烷基环；R16 是氢或 1 至 4 个碳原子的烷基；R17 和 R18 可以相同或不同，并且选自氢、卤素和烷基；n 是 0 或 1 至 4 的整数； X 是氧（-O-）、硫（-S-）、磺酰基（-SO 2 -）、亚砜基（-SO-）、硒基（-Se-）、羰基（-CO-）、氨基（-NH-）或亚甲基（- -）；其中取代基如本文所述。 此外，还提供了一种方法，用于预防、抑制或治疗与新陈代谢功能障碍有关的疾病或紊乱，或依赖于表达 T 3 调节基因的表达有关的疾病或紊乱的方法，其中上述化合物以治疗有效量给药。
• NOVEL THYROID RECEPTOR LIGANDS AND METHOD
  申请人：KARO BIO AB

  公开号：EP1000008B1

  公开（公告）日：2003-06-25