4-(5-Cyano-7-methyl-1,3-benzoxazol-2-yl)benzoic acid | 1093565-24-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(5-Cyano-7-methyl-1,3-benzoxazol-2-yl)benzoic acid
• CAS: 1093565-24-2
• 化学式: C₁₆H₁₀N₂O₃
• 分子量: 278.267
• InChiKey: LDDCTYKKEONKOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  87.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {1-[4-(trifluoromethyl)phenyl]piperidin-4-yl}methanamine 、 4-(5-Cyano-7-methyl-1,3-benzoxazol-2-yl)benzoic acid 在 草酰氯 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(5-cyano-7-methylbenzo[d]oxazol-2-yl)-N-methyl-N-((1-(4-(trifluoromethyl)phenyl)piperidin-4-yl)methyl)benzamide
  参考文献：
  名称：

  2-(4-Carbonylphenyl)benzoxazole inhibitors of CETP: Scaffold design and advancement in HDLc-raising efficacy

  摘要：

  The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Initial efforts aimed at engineering replacements for the aniline substructures in the benchmark molecule. Reversing the connectivity of the central aniline lead to a new class of 2-(4-carbonylphenyl)benzoxazoles. Structure-activity studies at the C-7 and terminal pyridine ring allowed for the optimization of potency and HDLc-raising efficacy in this new class of inhibitors. These efforts lead to the discovery of benzoxazole 11v, which raised HDLc by 24 mg/dl in our transgenic mouse PD model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.090
• 作为产物：
  描述：

  methyl 4-(5-cyano-7-methyl-1,3-benzoxazol-2-yl)benzoate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以97%的产率得到4-(5-Cyano-7-methyl-1,3-benzoxazol-2-yl)benzoic acid
  参考文献：
  名称：

  2-(4-Carbonylphenyl)benzoxazole inhibitors of CETP: Scaffold design and advancement in HDLc-raising efficacy

  摘要：

  The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Initial efforts aimed at engineering replacements for the aniline substructures in the benchmark molecule. Reversing the connectivity of the central aniline lead to a new class of 2-(4-carbonylphenyl)benzoxazoles. Structure-activity studies at the C-7 and terminal pyridine ring allowed for the optimization of potency and HDLc-raising efficacy in this new class of inhibitors. These efforts lead to the discovery of benzoxazole 11v, which raised HDLc by 24 mg/dl in our transgenic mouse PD model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.090

文献信息

• CETP INHIBITORS DERIVED FROM BENZOXAZOLE ARYLAMIDES
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2170058A1

  公开（公告）日：2010-04-07
• [EN] CETP INHIBITORS DERIVED FROM BENZOXAZOLE ARYLAMIDES<br/>[FR] INHIBITEURS DE CETP DÉRIVÉS DE BENZOXAZOLE ARYLAMIDES
  申请人：MERCK & CO INC

  公开号：WO2008156715A1

  公开（公告）日：2008-12-24

  [EN] Compounds having the structure of Formula I1 including pharmaceutically acceptable salts of the compounds, are potent CETP (cholesterol ester transfer protein) inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis Atherosclerosis and its clinical consequences, coronary heart disease (CHD), stroke and penpheral vascular disease, represent a truly enormous burden to the health care systems ofthe industrialized world In formula I, A-B is an arylamide moiety
  [FR] L'invention concerne des composés présentant une structure de formule I, ainsi que des sels acceptables sur le plan pharmaceutique desdits composés, qui sont de puissants inhibiteurs de CETP (protéine de transfert des esters de cholestérol), qui sont utiles pour augmenter le HDL cholestérol, réduire le LDL cholestérol, et qui permettent de traiter ou de prévenir l'athérosclérose. L'athérosclérose et ses conséquences cliniques, les coronaropathies (CHD), les AVC et maladies vasculaires périphériques, représentent un véritable fardeau pour les systèmes de soins de santé dans le monde industrialisé. Dans la formule I, A-B est un fragment arylamide.