methyl 2-cyclohexylmethoxy-4-benzyloxybenzoate | 170281-79-5

• 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-cyclohexylmethoxy-4-benzyloxybenzoate
• 英文别名: Methyl 2-(cyclohexylmethoxy)-4-phenylmethoxybenzoate
• CAS: 170281-79-5
• 化学式: C₂₂H₂₆O₄
• 分子量: 354.446
• InChiKey: LRXWIPLCIMYFDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 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：

  methyl 2-cyclohexylmethoxy-4-benzyloxybenzoate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以65%的产率得到4-benzyloxy-2-cyclohexylmethoxybenzoic 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：

  2,4-二羟基苯甲酸甲酯 在 四丁基氯化铵 、 sodium hydride 、 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 反应 31.17h， 生成 methyl 2-cyclohexylmethoxy-4-benzyloxybenzoate
  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

文献信息

• 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.
• Selective endothelin A receptor ligands. 1. Discovery and structure-activity of 2,4-disubstituted benzoic acid derivatives
  作者：PC Astles、TJ Brown、CM Handscombe、MF Harper、NV Harris、RA Lewis、PM Lockey、C McCarthy、IM McLay、B Porter、AG Roach、C Smith、RJA Walsh

  DOI：10.1016/s0223-5234(97)81678-9

  日期：1997.5

  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.