KB-131092 | 219691-88-0

• 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: KB-131092
• 英文别名: 3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid；2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid
• CAS: 219691-88-0
• 化学式: C₁₇H₁₆Br₂O₄
• 分子量: 444.12
• InChiKey: FDLOBNTWQDSHPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 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：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  KB-131092 在 sodium hydroxide 、 TEA 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 L-N-[3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl]alanine
  参考文献：
  名称：

  Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-α-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141

  摘要：

  Based on the scaffold of the pharmacologically selective thyromimetic 2b, structurally a close analog to KB-141 (2a), a number of novel N-acylated-alpha-amino acid derivatives were synthesized and tested in a TR radioligand binding assay as well as in a reporter cell assay. On the basis of TR beta(1)-isoform selectivity and affinity, as well as affinity to the reporter cell assay, 3d was selected for further studies in the cholesterol-fed rat model. In this model 3d revealed an improved therapeutic window between cholesterol and TSH lowering but decreased margins versus tachycardia compared with 2a. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.049
• 作为产物：
  描述：

  3,5-二溴-4-羟基苯乙酸甲酯 在 三溴化硼 、 铜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 KB-131092
  参考文献：
  名称：

  甲状腺受体配体。1.对甲状腺受体beta1具有选择性的激动剂配体。

  摘要：

  内源性甲状腺受体激素3,5,3'，5'-四碘-1-甲状腺素（T（4），1）和3,5,3'-三碘-1-甲状腺素（T（3），2）对哺乳动物的生长，发育和体内平衡具有重大影响。它们调节肠，骨骼和心肌，肝脏和中枢神经系统中的重要基因，影响整体代谢率，胆固醇和甘油三酸酯水平和心率，并影响情绪和整体幸福感。文献表明，甲状腺激素对心脏的许多或大多数作用，特别是对心率和节律的影响，是通过TRalpha（1）亚型介导的，而大多数激素对肝脏和其他组织的作用更多地是通过甲状腺激素介导的。受体的TRbeta（1）同工型。如果可以将不良反应减至最小或消除，则甲状腺激素的某些作用可能在非甲状腺疾病中具有治疗作用。这些潜在有用的功能包括：减轻体重以治疗肥胖症；降低胆固醇以治疗高血脂症；减轻抑郁症；以及刺激骨质疏松症中的骨形成。先前在药理上利用甲状腺激素治疗这些疾病的尝试受到甲亢的表现，特别是心血管毒性的限制。因此，对β

  DOI：

  10.1021/jm021080f

文献信息

• 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。
• Thyroid receptor ligands and method II
  申请人：Karo Bio AB

  公开号：US07288571B2

  公开（公告）日：2007-10-30

  New thyroid receptor ligands are provided which have general formula (I) in which: n is an integer from 0 to 4; R1 is halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons; 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, at least one of R2 and R3 being other than hydrogen; R4 is a carboxylic acid amide (CONR′R″) or an acylsulphonamide (CONHSO2R′) derivative, or a pharmaceutically acceptable salt thereof, and all stereolsom thereof; or when n is equal to or greater than one, R4 may be heteroaromatic moiety which may be substituted or unsubstituted, or an amine (NR′R″). R5 is hydrogen or an acyl (such as acetyl or benzoyl) or other group capable of bioconversion to generate the free phenol structure (wherein R5—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 T3 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 T3 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，其具有一般式（I），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，以及所有立体异构体；或当n等于或大于1时，R4可以是杂环芳基基团，可以是取代或未取代的，或者是胺（NR′R″）。R5是氢或酰基（例如乙酰或苯甲酰）或其他能够生物转化为生成自由酚结构（其中R5-H）的基团。此外，提供了一种用于预防、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的方法，其中以上述化合物以治疗有效量的方式给予。与代谢功能障碍相关或依赖于T3调节基因表达的这些疾病的示例包括肥胖症、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。
• NOVEL THYROID RECEPTOR LIGANDS AND METHOD
  申请人：KARO BIO AB

  公开号：EP1000008B1

  公开（公告）日：2003-06-25
• THYROID RECEPTOR LIGANDS
  申请人：KARO BIO AB

  公开号：EP1144370A2

  公开（公告）日：2001-10-17
• METHOD OF TREATING HAIR LOSS
  申请人：UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER

  公开号：EP1185229A1

  公开（公告）日：2002-03-13