2-(3-(2-(2-(tert-butyl)-4-chlorophenoxy)ethyl)-3-methylureido)benzoic acid

• 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-(3-(2-(2-(tert-butyl)-4-chlorophenoxy)ethyl)-3-methylureido)benzoic acid
• 英文别名: 2-(3-(2-(2-(Tert-butyl)-4-chlorophenoxy)ethyl)-3-methylureido) benzoic acid；2-[[2-(2-tert-butyl-4-chlorophenoxy)ethyl-methylcarbamoyl]amino]benzoic acid
• 化学式: C₂₁H₂₅ClN₂O₄
• 分子量: 404.894
• InChiKey: ABVXFUIMBDWVRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(叔丁基)-4-氯苯酚 在 盐酸 、 sodium tetrahydroborate 、 lithium hydroxide monohydrate 、 caesium carbonate 、 戴斯-马丁氧化剂 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 生成 2-(3-(2-(2-(tert-butyl)-4-chlorophenoxy)ethyl)-3-methylureido)benzoic acid
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Nonretinoid Retinol Binding Protein 4 Antagonists for the Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease

  摘要：

  Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4(-/-). mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.

  DOI：

  10.1021/jm5010013

文献信息

• [EN] N-ALKYL-2-PHENOXYETHANAMINES, THEIR PREPARATION AND USE<br/>[FR] N-ALKYL-2-PHÉNOXYÉTHANAMINES, LEURS PRÉPARATION ET UTILISATION
  申请人：UNIV COLUMBIA

  公开号：WO2014151959A1

  公开（公告）日：2014-09-25

  The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is alkyl; A is absent or present, and when present is -C(O)- or -C(O)NH-; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is -C(O)-, or a pharmaceutically acceptable salt thereof.

  本发明提供一种具有以下结构的化合物：（结构表示）其中R1、R2、R3、R4和R5分别独立地为H、卤素、CF3或C1-C4烷基；R6为烷基；A为不存在或存在，当存在时为-C(O)-或-C(O)NH-；B为取代或未取代的单环、双环、杂单环、杂双环、苄基、CO2H或（C1-C4烷基）-CO2H，其中当B为CO2H时，A存在且为-C(O)-，或其药用盐。
• N-ALKYL-2-PHENOXYETHANAMINES, THEIR PREPARATION AND USE
  申请人：PETRUKHIN Konstantin

  公开号：US20160046649A1

  公开（公告）日：2016-02-18

  The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is alkyl; A is absent or present, and when present is —C(O)— or —C(O)NH—; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is —C(O)—, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种具有以下结构的化合物：（结构表示）其中R1、R2、R3、R4和R5各自独立地为H、卤素、CF3或C1-C4烷基；R6为烷基；A不存在或存在，当存在时为—C（O）—或—C（O）NH—；B为取代或未取代的单环、双环、杂单环、杂双环、苄基、CO2H或（C1-C4烷基）-CO2H，其中当B为CO2H时，A存在且为—C（O）—，或其药学上可接受的盐。
• N-alkyl-2-phenoxyethanamines, their preparation and use
  申请人：The Trustees of Columbia University In the City of New York

  公开号：US10570148B2

  公开（公告）日：2020-02-25

  The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is alkyl; A is absent or present, and when present is —C(O)— or —C(O)NH—; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is —C(O)—, or a pharmaceutically acceptable salt thereof.

  本发明提供了一种具有以下结构的化合物：(结构表示），其中 R1、R2、R3、R4 和 R5 各自独立地为 H、卤素、CF3 或 C1-C4 烷基；R6 为烷基；A 不存在或存在，存在时为 -C(O)- 或 -C(O)NH- ；B 为取代或未取代的单环、单车、杂单环、杂单车、苄基、CO2H 或 (C1-C4 烷基)-CO2H，其中当 B 为 CO2H 时，则 A 存在且为 -C(O)-，或其药学上可接受的盐。
• US9938291B2
  申请人：——

  公开号：US9938291B2

  公开（公告）日：2018-04-10
• [EN] RBP4 ANTAGONISTS FOR TREATMENT AND PREVENTION OF NON-ALCOHOLIC FATTY LIVER DISEASE AND GOUT<br/>[FR] ANTAGONISTES DE RBP4 POUR LE TRAITEMENT ET LA PRÉVENTION DE LA STÉATOSE HÉPATIQUE NON ALCOOLIQUE ET DE LA GOUTTE
  申请人：UNIV COLUMBIA

  公开号：WO2020028723A1

  公开（公告）日：2020-02-06

  The subject invention provides a method for treating a non-alcoholic fatty liver disease (NAFLD) disease in a subject afflicted therewith comprising administering to the subject a pharmaceutical composition comprising an amount of a compound which is a non-retinoid retinol- binding protein 4 (RBP4) antagonist effective to treat the subject, thereby treating the subject. The subject invention provides a method for treating gout in a subject afflicted therewith comprising administering to the subject a pharmaceutical composition comprising an amount of a compound which is a retinol-binding protein 4 (RBP4) antagonist effective to treat the subject, thereby treating the subject.