3-(benzyloxy)-5-chlorobenzoic acid | 53985-44-7

• 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: 3-(benzyloxy)-5-chlorobenzoic acid
• 英文别名: 3-benzyloxy-5-chlorobenzoic acid；KSC-392-023；3-Benzyloxy-5-chlor-benzoesaeure；3-Benzyloxy-5-chlorbenzoesaeure；3-(Benzoxy)-5-chlorobenzoic acid；3-chloro-5-phenylmethoxybenzoic acid
• CAS: 53985-44-7
• 化学式: C₁₄H₁₁ClO₃
• 分子量: 262.693
• InChiKey: KJGCTENTYBZIAT-UHFFFAOYSA-N

物化性质

• 沸点：
  432.6±30.0 °C(Predicted)
• 密度：
  1.322±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-5-chlorobenzoic acid 在 lithium aluminium tetrahydride 、 二苯基膦叠氮化物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.0h， 生成 [3-(Benzyloxy)-5-chlorophenyl]methanamine
  参考文献：
  名称：

  3-Aminopyrrolidinone Farnesyltransferase Inhibitors:  Design of Macrocyclic Compounds with Improved Pharmacokinetics and Excellent Cell Potency

  摘要：

  A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic properties with a reduced potential for side effects. In dogs, oral bioavailability was good to excellent, and increases in plasma half-life were due to attenuated clearance. It was observed that in vivo clearance correlated with the flexibility of the molecules and this concept proved useful in the design of FTIs that exhibited low clearance, such as FTI 78. X-ray crystal structures of compounds 49 and 66 complexed with farnesyltransferase (FTase)-farnesyl diphosphate (FPP) were determined, and they provide details of the key interactions in such ternary complexes. Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date.

  DOI：

  10.1021/jm010531d
• 作为产物：
  描述：

  3,5-二氯苯酚 在 caesium carbonate 、 magnesium 、 碘甲烷 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 3-(benzyloxy)-5-chlorobenzoic acid
  参考文献：
  名称：

  3-Aminopyrrolidinone Farnesyltransferase Inhibitors:  Design of Macrocyclic Compounds with Improved Pharmacokinetics and Excellent Cell Potency

  摘要：

  A series of macrocyclic 3-aminopyrrolidinone farnesyltransferase inhibitors (FTIs) has been synthesized. Compared with previously described linear 3-aminopyrrolidinone FTIs such as compound 1, macrocycles such as 49 combined improved pharmacokinetic properties with a reduced potential for side effects. In dogs, oral bioavailability was good to excellent, and increases in plasma half-life were due to attenuated clearance. It was observed that in vivo clearance correlated with the flexibility of the molecules and this concept proved useful in the design of FTIs that exhibited low clearance, such as FTI 78. X-ray crystal structures of compounds 49 and 66 complexed with farnesyltransferase (FTase)-farnesyl diphosphate (FPP) were determined, and they provide details of the key interactions in such ternary complexes. Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date.

  DOI：

  10.1021/jm010531d

文献信息

• [EN] SMALL MOLECULE INHIBITORS OF THE MITOCHONDRIAL PERMEABILITY TRANSITION PORE (mtPTP)<br/>[FR] PETITES MOLÉCULES INHIBITRICES DU PORE DE TRANSITION DE PERMÉABILITÉ MITOCHONDRIALE (MTPTP)
  申请人：UNIV KANSAS

  公开号：WO2016073633A1

  公开（公告）日：2016-05-12

  The present technology relates to compounds of any one of Formula I, II, IIa, III, IV, and/or V as described herein and their tautomers and/or pharmaceutically acceptable salts, compositions, and methods of uses thereof.

  目前的技术涉及到本文描述的任一式I、II、IIa、III、IV和/或V的化合物，以及它们的互变异构体和/或药用盐、组合物以及使用方法。
• Inhibitors of prenyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US06441017B1

  公开（公告）日：2002-08-27

  The present invention is directed to macrocyclic compounds which inhibit prenyl-protein transferase (FTase) and the prenylation of the oncogene protein Ras. The invention is further directed to chemothera-peutic compositions containing the compounds of this invention and methods for inhibiting prenyl-protein transferase and the prenylation of the oncogene protein Ras.

  本发明涉及抑制萜基-蛋白转移酶（FTase）和致癌基因蛋白Ras的大环化合物。该发明还涉及含有本发明化合物的化疗组合物以及抑制萜基-蛋白转移酶和致癌基因蛋白Ras的方法。
• Substituted benzoic acid hypolipemic agents
  申请人：Pfizer Inc.

  公开号：US03953595A1

  公开（公告）日：1976-04-27

  Polysubstituted benzoic acids, and their use in mammals as hypolipemic agents.

  多取代苯甲酸及其在哺乳动物中作为降血脂剂的应用。
• [EN] BIARYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS<br/>[FR] DÉRIVÉS D'ACIDE BIARYL-PROPIONIQUE ET LEUR UTILISATION EN TANT QUE PRODUITS PHARMACEUTIQUES
  申请人：SANOFI SA

  公开号：WO2014154727A1

  公开（公告）日：2014-10-02

  The present invention relates to compounds of the formula (I), wherein X, R, R1, R2, D, E1, E2, E3, E4, G1, G2, G3 and G4 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease cathepsin A, and are useful for the treatment of diseases such as atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula (I), their use and pharmaceutical compositions comprising them.

  本发明涉及式(I)的化合物，其中X、R、R1、R2、D、E1、E2、E3、E4、G1、G2、G3和G4在权利要求中所示的含义，这些化合物是有价值的药用活性化合物。它们是蛋白酶卡特普辛A的抑制剂，可用于治疗动脉粥样硬化、心力衰竭、肾脏疾病、肝脏疾病或炎症性疾病等疾病。此外，本发明还涉及制备式(I)化合物的方法，它们的用途以及包含它们的药物组合物。
• <i>N</i>-Phenylbenzamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore
  作者：Sudeshna Roy、Justina Šileikytė、Benjamin Neuenswander、Michael P. Hedrick、Thomas D. Y. Chung、Jeffrey Aubé、Frank J. Schoenen、Michael A. Forte、Paolo Bernardi

  DOI：10.1002/cmdc.201500545

  日期：2016.2

  the mitochondrial permeability transition pore (PTP), an inner membrane channel, leads to mitochondrial dysfunction and renders the PTP a therapeutic target for a host of life‐threatening diseases. Herein, we report our effort toward identifying small‐molecule inhibitors of this target through structure–activity relationship optimization studies, which led to the identification of several potent analogues

  内膜通道线粒体通透性过渡孔（PTP）的持续打开会导致线粒体功能障碍，并使PTP成为许多威胁生命的疾病的治疗靶标。本文中，我们报告了我们通过结构-活性关系优化研究确定该目标的小分子抑制剂的努力，该研究导致通过高通量筛选鉴定了N-苯基苯甲酰胺化合物系列附近的几种有效类似物。特别是化合物4（3-（苄氧基）-5-氯-N-（4-（哌啶-1-基甲基）苯基）苯甲酰胺）在线粒体溶胀试验中显示出显着的抑制活性（EC 50 = 280 n m），理化性能差到很好以及体外药代动力学特性，并赋予线粒体很高的钙保留能力。从数据来看，我们认为该系列化合物 4代表了具有药理学意义的PTP抑制剂的发展前景。