ethyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate | 1245617-64-4

• 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: ethyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
• 英文别名: 2-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid ethyl ester
• CAS: 1245617-64-4
• 化学式: C₁₆H₂₃BO₄
• 分子量: 290.167
• InChiKey: SQYOCUYUOZHWFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.47
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate 、 3-(3-fluoro-5-(trifluoromethyl)benzyl)-1-methyl-1H-pyrazol-5-yl trifluoromethanesulfonate 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 以86%的产率得到ethyl 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-1-methyl-1Hpyrazol-5-yl)-2-methylbenzoate
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of 4-azolyl-benzamide derivatives as novel GPR52 agonists

  摘要：

  G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzy1)-5-methyl-1H-1,2,4-triazol-1-y1)-2-methylbenzamide (4u; half maximal effective concentration (EC50) = 75 nM, maximal response (E-max) = 122%) starting from a high-throughput screening hit 3 (EC50 = 470 nM, E-max = 56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists. A structure-activity relationship study of 4-azolylbenzamide resulted in the design of the 1,2,4-triazole derivative 4u, which demonstrated excellent bioavailability in rats (F = 53.8%). Oral administration of 4u (10 mg/kg) significantly suppressed methamphetamine-induced hyperlocomotion in mice. Thus, 4u is a promising lead compound for drug discovery research of GPR52 agonists. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.03.064
• 作为产物：
  描述：

  对甲苯甲酸 在 (1,5-cyclooctadiene)(methoxy)iridium(I) dimer 、 硫酸 、 8-([2,2'-bipyridin]-5-yl)quinolin-2(1H)-one 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 ethyl 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
  参考文献：
  名称：

  Ir催化的C–H活化中的非共价相互作用：L型配体，用于芳族酯的部分选择性硼化反应

  摘要：

  描述了一种用于芳族酯的对位选择性硼化的有效策略。为了获得高的对位选择性，已经开发了一种新的催化体系，该体系改变了联吡啶的核心结构。有人提出，L型配体对于通过非共价相互作用识别酯羰基的氧原子的功能至关重要，这为超选择性C–H活化/硼化提供了空前的控制因素。

  DOI：

  10.1021/jacs.7b04490

文献信息

• [EN] 1,1-(Dimethyl-Ethylamino)-2-Hydroxy-Propoxy]-Ethyl}-3-Methyl-Biphenyl-4- Carboxylic Acid Derivatives As Calcium Receptor Antagonists<br/>[FR] DÉRIVÉS DE L'ACIDE 1,1-(DIMÉTHYL-ÉTHYLAMINO)-2-HYDROXY-PROPOXY]-ÉTHYL}-3-MÉTHYL-BIPHÉNYL-4-CARBOXYLIQUE UTILES EN TANT QU'ANTAGONISTES DES RÉCEPTEURS DU CALCIUM
  申请人：PFIZER

  公开号：WO2010103429A1

  公开（公告）日：2010-09-16

  The present invention is directed to novel 1,1 -(dimethyl-ethylamino)-2- hydroxy-propoxy]-ethyl}-3-methyl-biphenyl-4-carboxylic acid derivatives and pharmaceutically acceptable salts thereof of structural formula I wherein the variable R1 is as described herein. Also provided are pharmaceutical compositions comprising the compounds of formula I as well as methods of treatment employing compounds of formula I to treat a disease or disorder characterized by abnormal bone or mineral homeostasis such as hypoparathyroidism, osteoporosis, osteopenia, periodontal disease, Paget's disease, bone fracture, osteoarthritis, rheumatoid arthritis, and humoral hypercalcemia of malignancy.

  本发明涉及新颖的1,1-(二甲基乙基氨基)-2-羟基-丙氧基]-乙基}-3-甲基联苯基-4-羧酸衍生物及其结构式I中的药用盐，其中变量R1如本文所述。还提供了包含结构式I化合物的药物组合物，以及利用结构式I化合物治疗由异常骨骼或矿物质稳态特征的疾病或紊乱的方法，如甲状旁腺功能减退症、骨质疏松症、骨质疏松症、牙周病、帕吉特病、骨折、骨关节炎、类风湿性关节炎和恶性高钙血症。