2-[(4'-tert-butoxybiphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid benzyl ester

• 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-[(4'-tert-butoxybiphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid benzyl ester
• 英文别名: Benzyl 2-[[2-[4-[(2-methylpropan-2-yl)oxy]phenyl]benzoyl]amino]quinoline-6-carboxylate
• 化学式: C₃₄H₃₀N₂O₄
• 分子量: 530.623
• InChiKey: ADQANXPUVJKJBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(4'-tert-butoxybiphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid benzyl ester 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 2-[(4'-tert-butoxybiphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid
  参考文献：
  名称：

  Discovery of microsomal triglyceride transfer protein (MTP) inhibitors with potential for decreased active metabolite load compared to dirlotapide

  摘要：

  Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activity of likely human metabolites and increasing metabolite clearance to reduce exposure. Introduction of 4'-alkyl and 4'-alkoxy substituents afforded compounds exhibiting improved therapeutic index in rats with respect to liver triglyceride accumulation and enzyme elevation. Likely human metabolites of select compounds were prepared and characterized for their potential to inhibit MTP in vivo. Based on preclinical efficacy and safety data and its potential for producing short-lived, weakly active metabolites, compound 13 (PF-02575799) advanced into phase 1 clinical studies. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.099
• 作为产物：
  描述：

  喹啉-6-羧酸苄基酯 在 4-二甲氨基吡啶 、 苯酐 、 过氧化脲素 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-[(4'-tert-butoxybiphenyl-2-carbonyl)-amino]-quinoline-6-carboxylic acid benzyl ester
  参考文献：
  名称：

  Discovery of microsomal triglyceride transfer protein (MTP) inhibitors with potential for decreased active metabolite load compared to dirlotapide

  摘要：

  Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activity of likely human metabolites and increasing metabolite clearance to reduce exposure. Introduction of 4'-alkyl and 4'-alkoxy substituents afforded compounds exhibiting improved therapeutic index in rats with respect to liver triglyceride accumulation and enzyme elevation. Likely human metabolites of select compounds were prepared and characterized for their potential to inhibit MTP in vivo. Based on preclinical efficacy and safety data and its potential for producing short-lived, weakly active metabolites, compound 13 (PF-02575799) advanced into phase 1 clinical studies. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.099

文献信息

• [EN] SUBSTITUTED QUINOLINE COMPOUNDS<br/>[FR] COMPOSES DE QUINOLINE SUBSTITUES
  申请人：PFIZER PROD INC

  公开号：WO2005080373A1

  公开（公告）日：2005-09-01

  This invention relates to MTP/Apo-B secretion inhibitors of Formula (I) wherein R1-R7, X1, m and n are as defined in the specification, as well as pharmaceutical compositions comprising the compounds, and methods of use of the compounds and compositions. The compounds of the invention are useful in treating obesity and associated diseases, conditions or disorders.

  本发明涉及式(I)的MTP/Apo-B分泌抑制剂，其中R1-R7、X1、m和n的定义如说明书中所述，以及包含这些化合物的药物组合物，以及这些化合物和组合物的使用方法。本发明的化合物可用于治疗肥胖及其相关疾病、状况或失调。
• Substituted quinoline compounds
  申请人：Bertinato Peter

  公开号：US20050234099A1

  公开（公告）日：2005-10-20

  This invention relates to MTP/Apo-B secretion inhibitors of Formula (I) wherein R 1 -R 7 , X 1 , m and n are as defined in the specification, as well as pharmaceutical compositions comprising the compounds, and methods of use of the compounds and compositions. The compounds of the invention are useful in treating obesity and associated diseases, conditions or disorders.

  本发明涉及公式（I）中的MTP / Apo-B分泌抑制剂，其中R1-R7，X1，m和n如规范中所定义，以及包含该化合物的制药组合物，以及该化合物和组合物的使用方法。本发明的化合物在治疗肥胖和相关疾病，状况或障碍方面是有用的。
• TRIAMIDE-SUBSTITUTED HETEROBICYCLIC COMPOUNDS
  申请人：Bertinato Peter

  公开号：US20060223851A1

  公开（公告）日：2006-10-05

  This invention relates to MTP/Apo-B secretion inhibitors of Formula (I) wherein R 1 -R 7 , X 1 , m and n are as defined in the specification, as well as pharmaceutical compositions comprising the compounds, and methods of use of the compounds and compositions. The compounds of the invention are useful in treating obesity and associated diseases, conditions or disorders.

  本发明涉及公式（I）中的MTP / Apo-B分泌抑制剂，其中R1-R7，X1，m和n如规范中定义，以及包含该化合物的制药组合物和该化合物和组合物的使用方法。本发明的化合物在治疗肥胖及其相关疾病，情况或障碍方面有用。
• Triamide-substituted heterobicyclic compounds
  申请人：Bertinato Peter

  公开号：US20070093525A1

  公开（公告）日：2007-04-26

  This invention relates to MTP/Apo-B secretion inhibitors of Formula (I) wherein R 1 -R 7 , X 1 , m and n are as defined in the specification, as well as pharmaceutical compositions comprising the compounds, and methods of use of the compounds and compositions. The compounds of the invention are useful in treating obesity and associated diseases, conditions or disorders.

  本发明涉及公式(I)中的MTP / Apo-B分泌抑制剂，其中R1-R7，X1，m和n如说明书中所定义，以及包含该化合物的制药组合物，以及使用该化合物和组合物的方法。该发明的化合物对于治疗肥胖症及其相关疾病、病况或障碍具有用途。
• SUBSTITUTED QUINOLINE COMPOUNDS
  申请人：Pfizer Products Incorporated

  公开号：EP1716137A1

  公开（公告）日：2006-11-02