3-(3-thienylmethoxy)phenol | 211108-25-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(3-thienylmethoxy)phenol
• 英文别名: 3-(thiophen-3-ylmethoxy)phenol
• CAS: 211108-25-7
• 化学式: C₁₁H₁₀O₂S
• 分子量: 206.265
• InChiKey: MZNHXCYUCOVIMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-thienylmethoxy)phenol 在 氢氧化钾 、 potassium carbonate 、 potassium iodide 作用下， 以 甲醇 、 丁酮 为溶剂， 反应 48.5h， 生成 4-[3-(Thiophen-3-ylmethoxy)-phenoxy]-4-o-tolyl-butyric acid
  参考文献：
  名称：

  Selective Endothelin A Receptor Antagonists. 3. Discovery and Structure−Activity Relationships of a Series of 4-Phenoxybutanoic Acid Derivatives

  摘要：

  The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated. These include hypertension, ischemic diseases, and atherosclerosis. In earlier publications we have outlined the discovery and structure-activity relations of two moderately potent series of nonpeptide ETA receptor antagonists. In this paper, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these two series of compounds to be merged into a single class of 4-phenoxybutanoic acid derivatives. The subsequent optimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid (12m). This compound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity over the ETB receptor. Data are presented to demonstrate that 12m is orally bioavailable in the rat and is a functional antagonist in vitro and in vivo of ET-1-induced vasoconstriction.

  DOI：

  10.1021/jm9707131
• 作为产物：
  描述：

  3-氯甲基噻吩 、 间苯二酚 在 四丁基溴化铵 、 potassium carbonate 、 potassium iodide 作用下， 以 丁酮 为溶剂， 反应 5.0h， 以27%的产率得到3-(3-thienylmethoxy)phenol
  参考文献：
  名称：

  Selective Endothelin A Receptor Antagonists. 3. Discovery and Structure−Activity Relationships of a Series of 4-Phenoxybutanoic Acid Derivatives

  摘要：

  The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated. These include hypertension, ischemic diseases, and atherosclerosis. In earlier publications we have outlined the discovery and structure-activity relations of two moderately potent series of nonpeptide ETA receptor antagonists. In this paper, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these two series of compounds to be merged into a single class of 4-phenoxybutanoic acid derivatives. The subsequent optimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid (12m). This compound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity over the ETB receptor. Data are presented to demonstrate that 12m is orally bioavailable in the rat and is a functional antagonist in vitro and in vivo of ET-1-induced vasoconstriction.

  DOI：

  10.1021/jm9707131

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.
• Selective Endothelin A Receptor Antagonists. 3. Discovery and Structure−Activity Relationships of a Series of 4-Phenoxybutanoic Acid Derivatives
  作者：Peter C. Astles、Clive Brealey、Thomas J. Brown、Vincenzo Facchini、Caroline Handscombe、Neil V. Harris、Clive McCarthy、Iain M. McLay、Barry Porter、Alan G. Roach、Carol Sargent、Christopher Smith、Roger J. A. Walsh

  DOI：10.1021/jm9707131

  日期：1998.7.1

  The third in this series of papers describes our further progress into the discovery of a potent and selective endothelin A (ETA) receptor antagonist for the potential treatment of diseases in which a pathophysiological role for endothelin has been implicated. These include hypertension, ischemic diseases, and atherosclerosis. In earlier publications we have outlined the discovery and structure-activity relations of two moderately potent series of nonpeptide ETA receptor antagonists. In this paper, we describe how a pharmacophore model for ETA receptor binding was developed which enabled these two series of compounds to be merged into a single class of 4-phenoxybutanoic acid derivatives. The subsequent optimization of in vitro activity against the ETA receptor led to the discovery of (R)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid (12m). This compound exhibits low-nanomolar binding to the ETA receptor and a greater than 1000-fold selectivity over the ETB receptor. Data are presented to demonstrate that 12m is orally bioavailable in the rat and is a functional antagonist in vitro and in vivo of ET-1-induced vasoconstriction.