ethyl (RS)-4-[2-(4,5-dihydrooxazol-2-yl)-5-(thien-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate | 170282-62-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: ethyl (RS)-4-[2-(4,5-dihydrooxazol-2-yl)-5-(thien-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate
• 英文别名: ethyl (RS)-4-[2-(4,5-dihydrooxazol-2-yl)-5-(3-thienylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate；ethyl 4-[2-(4,5-dihydro-1,3-oxazol-2-yl)-5-(thiophen-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate
• CAS: 170282-62-9
• 化学式: C₂₇H₂₉NO₅S
• 分子量: 479.597
• InChiKey: AOMONWBMWZOBJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  94.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl (RS)-4-[2-(4,5-dihydrooxazol-2-yl)-5-(thien-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate 在 黑色氧化镍 silica 、 乙酸乙酯 、 环己烷 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以to give ethyl (RS)-4-[2-(oxazol-2-yl)-5-(3-thienylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate (140 mg)的产率得到ethyl (RS)-4-[2-(oxazol-2-yl)-5-(thien-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate
  参考文献：
  名称：

  Substituted phenyl compounds

  摘要：

  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。

  公开号：

  US06211234B1
• 作为产物：
  描述：

  2-Hydroxy-N-(2-hydroxy-ethyl)-4-(thiophen-3-ylmethoxy)-benzamide 在 methoxycarbonylsulfamoyl-triethylammmonium hydroxide 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 ethyl (RS)-4-[2-(4,5-dihydrooxazol-2-yl)-5-(thien-3-ylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate
  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