Methyl 2-hydroxy-4-(3-methoxybenzyloxy)benzoate | 1027284-00-9

• 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: Methyl 2-hydroxy-4-(3-methoxybenzyloxy)benzoate
• 英文别名: methyl 2-hydroxy-4-[(3-methoxyphenyl)methoxy]benzoate
• CAS: 1027284-00-9
• 化学式: C₁₆H₁₆O₅
• 分子量: 288.3
• InChiKey: SSQACFXTSOXXNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Methyl 2-hydroxy-4-(3-methoxybenzyloxy)benzoate 在 sodium hydroxide 、 sodium hydride 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-[(3-Methoxyphenyl)methoxy]-2-phenylmethoxybenzoic acid
  参考文献：
  名称：

  Selective endothelin A receptor ligands. 1. Discovery and structure-activity of 2,4-disubstituted benzoic acid derivatives

  摘要：

  This paper describes the discovery of a new non-peptide endothelin A (ETA) selective ligand, 2,4-dibenzyloxybenzoic acid 3, which inhibits the binding of [I-125]ET-1 to ETA receptors with an IC50 of 9 mu M (ET-1 = endothelin-1). Optimisation of 3 resulted in compound 52 which had an IC50 of 1 mu M. One of the analogues of 3, compound 15, was examined in a functional assay and shown to antagonise ET-1-induced contraction of rat aorta. The identification of 3 was made through the application of ChemDBS-3D searching of our corporate database. The 3D query, using an aromatic ring to a carboxylic acid group separated by 10.2 +/- 1.1 Angstrom, was derived from an examination of common pharmacophoric distances found in the low energy conformations of two known ETA antagonists, the cyclic pentapeptide BQ 123 1 and myriceron caffeoyl ester 2.

  DOI：

  10.1016/s0223-5234(97)81678-9
• 作为产物：
  描述：

  间甲氧基苯甲醇 在 吡啶 、 氯化亚砜 、 四丁基溴化铵 、 potassium carbonate 、 potassium iodide 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 6.0h， 生成 Methyl 2-hydroxy-4-(3-methoxybenzyloxy)benzoate
  参考文献：
  名称：

  Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity

  摘要：

  A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.01.003

文献信息

• Substituted phenyl compounds
  申请人：Rhone-Poulenc Rorer Limited

  公开号：US06211234B1

  公开（公告）日：2001-04-03

  Compounds of formula (I) are described wherein R1 is hydrogen, -(lower alkyl)q(CO2R6 or OH), —CN, —C(R7)═NOR8, NO2, —O(lower alkyl)R9, —C≡C—R10, —CR11═C(R12)(R13), —C(═O)CH2C(═O)CO2H, —CO(R14), alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, thiocarbamoyl, substituted carbamoyl, substituted thiocarbamoyl, sulphamoyl or an optionally substituted nitrogen-containing ring, m, n, o and p are independently zero or 1 and R2, R3, R4 and R5 are various groups; and physiologically acceptable salts, N-oxides and prodrugs thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.

  描述了化学式(I)的化合物，其中R1是氢，-(较低的烷基)q(CO2R6或OH)，—CN，—C(R7)═NOR8，NO2，—O(较低的烷基)R9，—C≡C—R10，—CR11═C(R12)(R13)，—C(═O)CH2C(═O)CO2H，—CO(R14)，烷基硫醇，烷基亚砜，烷基磺酰，氨基甲酰，硫代氨基甲酰，取代的氨基甲酰，取代的硫代氨基甲酰，磺酰胺或可选取代的含氮环，其中m，n，o和p独立地为零或1，而R2，R3，R4和R5是各种基团;以及其生理上可接受的盐，N-氧化物和前药。这些化合物具有内皮素拮抗剂活性，可用作药物。
• SUBSTITUTED PHENYL COMPOUNDS
  申请人：RHONE-POULENC RORER LIMITED

  公开号：EP0728128B1

  公开（公告）日：1998-09-16
• US6211234B1
  申请人：——

  公开号：US6211234B1

  公开（公告）日：2001-04-03
• [EN] SUBSTITUTED PHENYL COMPOUNDS<br/>[FR] COMPOSES PHENYLIQUES SUBSTITUES
  申请人：RHONE-POULENC RORER LIMITED

  公开号：WO1995013262A1

  公开（公告）日：1995-05-18

  (EN) Compounds of formula (I) are described wherein R1 is hydrogen, -(lower alkyl)q(CO2R6 or OH), -CN, -C(R7)=NOR8, NO2, -O(lower alkyl)R9, -C$m(0)C-R10, -CR11=C(R12)(R13), -C(=O)CH2C(=O)CO2H, -CO(R14), alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, thiocarbamoyl, substituted carbamoyl, substituted thiocarbamoyl, sulphamoyl or an optionally substituted nitrogen-containing ring, m, n, o and p are independently zero or 1 and R2, R3, R4 and R5 are various groups; and physiologically acceptable salts, N-oxides and prodrugs thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.(FR) L'invention concerne des composés de formule (I) dans laquelle R1 représente hydrogène, -(alkyle inférieur)q(CO2R6 ou OH), -CN, -C(R7)=NOR8, NO2, -O(alkyle inférieur)R9, -C$m(0)C-R10, -CR11=C(R12)(R13), -C(=O)CH2C(=O)CO2H, -CO(R14), alkylthio, alkylsulfinyle, alkylsulfonyle, carbamoyle, thiocarbamoyle, carbamoyle substitué, thiocarbamoyle substitué, sulfamoyle ou un cycle contenant de l'azote facultativement substitué, m, n, o et p représentent indépendamment zéro ou 1 et R2, R3, R4, et R5 représentent différents groupes. L'invention porte également sur des sels physiologiquement acceptables, des N-oxydes et des promédicaments de ces derniers. Ces composés présentent une activité d'antagonistes de l'endothéline et sont utiles en tant que produits pharmaceutiques.
• Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity
  作者：Jin Cai、Ligang Liu、Kwon Ho Hong、Peng Wang、Lushen Li、Meng Cao、Chunlong Sun、Xiaoqing Wu、Xi Zong、Junqing Chen、Min Ji

  DOI：10.1016/j.bmc.2015.01.003

  日期：2015.2

  A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases. (c) 2015 Elsevier Ltd. All rights reserved.