tert-butyl 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylate | 1381777-25-8

• 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: tert-butyl 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylate
• 英文别名: tert-butyl 2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylate；tert-butyl 5-(2,4-difluorophenyl)-2-hydroxybenzoate
• CAS: 1381777-25-8
• 化学式: C₁₇H₁₆F₂O₃
• 分子量: 306.309
• InChiKey: OXCGZFWPJSROHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylate 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 potassium carbonate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.08h， 生成 2-((3-(tert-butoxycarbonyl)-2',4'-difluoro-[1,1'-biphenyl]-4-yl)-oxy)acetic acid
  参考文献：
  名称：

  Peptide Half-Life Extension: Divalent, Small-Molecule Albumin Interactions Direct the Systemic Properties of Glucagon-Like Peptide 1 (GLP-1) Analogues

  摘要：

  Noncovalent binding of biopharmaceuticals to human serum albumin protects against enzymatic degradation and renal clearance. Herein, we investigated the effect of mono- cor divalent small-molecule albumin binders for half-life extension of peptides. For proof-of-principle, the clinically relevant glucagon-like peptide 1 (GLP-1) was functionalized with diflunisal, indomethacin, or both. In vitro, all GLP-1 analogues had subnanomolar GLP-1 receptor potency. Surface plasmon resonance revealed that both small molecules were able to confer albumin affinity to GLP-1 and indicated that affinity is increased for divalent analogues. In lean mice, the divalent GLP-1 analogues were superior to monovalent analogues with respect to control of glucose homeostasis and suppression of food intake. Importantly, divalent GLP-1 analogues showed efficacy comparable to liraglutide, an antidiabetic GLP-1 analogue that carries a long-chain fatty acid. Finally, pharmacokinetic investigations of a divalent GLP-1 analogue demonstrated a promising gain in circulatory half-life and absorption time compared to its monovalent equivalent.

  DOI：

  10.1021/acs.jmedchem.7b00787
• 作为产物：
  描述：

  二氟尼柳 、 叔丁醇 在 N,N'-羰基二咪唑 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 以68%的产率得到tert-butyl 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylate
  参考文献：
  名称：

  Thiocarbonates as Anti-Inflammatory and Antioxidant Compounds Useful For Treating Metabolic Disorders

  摘要：

  该发明涉及Formula (I)-(III)的硫代碳酸酯化合物以及治疗动脉硬化、神经病变、肾病、视网膜病变、炎症性疾病、慢性阻塞性肺病（COPD）、心血管疾病、代谢紊乱、1型糖尿病、2型糖尿病、LADA、Wolfram综合症1、Wolcott-Rallison综合症、代谢综合症、血脂异常、高血糖或胰岛素抵抗的方法。该发明的化合物还可用于保护胰岛β细胞，减少游离脂肪酸、甘油三酯、高级糖基化终产物、ROS、脂质过氧化、组织和血浆TNFα和IL6水平，或延缓或预防与动脉硬化相关的心血管并发症。

  公开号：

  US20120149769A1

文献信息

• Pharmaceutical Combinations Including Anti-Inflammatory and Antioxidant Conjugates Useful for Treating Metabolic Disorders
  申请人：Laria Julio Cesar Castro Palomino

  公开号：US20150025006A1

  公开（公告）日：2015-01-22

  One aspect of the present invention is a pharmaceutical combination comprising (a) an anti-inflammatory agent/anti-oxidant agent conjugate; and (b) an insulin secretogogue, an insulin sensitizer, an alpha-glucosidase inhibitor, a peptide analog, or a combination thereof. Another aspect of the invention relates to methods of treating metabolic disorders with such conjugates.

  本发明的一个方面是一种药物组合，包括（a）一种抗炎/抗氧化药物偶联物；以及（b）一种胰岛素分泌素、胰岛素敏感剂、α-葡萄糖苷酶抑制剂、肽类类似物或其组合。本发明的另一个方面涉及使用这种偶联物治疗代谢性疾病的方法。
• [EN] PHARMACEUTICAL COMBINATIONS INCLUDING ANTI-INFLAMMATORY AND ANTIOXIDANT CONJUGATES USEFUL FOR TREATING METABOLIC DISORDERS<br/>[FR] COMBINAISONS PHARMACEUTIQUES CONTENANT DES CONJUGUÉS ANTI-INFLAMMATOIRE- ANTIOXYDANT ET DESTINÉES À ÊTRE UTILISÉES EN VUE DU TRAITEMENT D'AFFECTIONS MÉTABOLIQUES
  申请人：GENMEDICA THERAPEUTICS SL

  公开号：WO2013037985A8

  公开（公告）日：2013-04-11
• PHARMACEUTICAL COMBINATIONS INCLUDING ANTI-INFLAMMATORY AND ANTIOXIDANT CONJUGATES USEFUL FOR TREATING METABOLIC DISORDERS
  申请人：Genmedica Therapeutics SL

  公开号：EP2755645A1

  公开（公告）日：2014-07-23
• US8466197B2
  申请人：——

  公开号：US8466197B2

  公开（公告）日：2013-06-18
• [EN] NEW THIOCARBONATES AS ANTI-INFLAMMATORY AND ANTIOXIDANT COMPOUNDS USEFUL FOR TREATING METABOLIC DISORDERS<br/>[FR] NOUVEAUX THIOCARBONATES EN TANT QUE COMPOSÉS ANTI-INFLAMMATOIRES ET ANTIOXYDANTS UTILES POUR LE TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：GENMEDICA THERAPEUTICS SL

  公开号：WO2012080371A1

  公开（公告）日：2012-06-21

  The invention is directed to thiocarbonate compounds of Formula (I)-( III) and methods of treating atherosclerosis, neuropathy, nephropathy, retinopathy, inflammatory disorders, COPD, cardiovascular diseases, metabolic disorders, type I diabetes mellitus, type II diabetes mellitus, LAD A, Wolfram Syndrome 1, Wolcott-Rallison syndrome, metabolic syndrome, dyslipidemia, hyperglycemia, or insulin resistance. The compounds of the invention are also useful for protecting pancreatic beta-cells and for reducing free fatty acids, triglycerides, advanced glycated end products, ROS, lipid peroxidation, tissue and plasma TNFalpha and IL6 levels, or for delaying or preventing cardiovascular complications associated with atherosclerosis.