methyl (RS)-5-[3-(hydroxy)phenyl]-4-(2-methylphenyl)-5-oxo-pentanoate | 170282-10-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: methyl (RS)-5-[3-(hydroxy)phenyl]-4-(2-methylphenyl)-5-oxo-pentanoate
• 英文别名: (+/-)-methyl 5-(3-hydroxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate；methyl (RS)-5-(3-hydroxyphenyl)-5-oxo-4-(2-methylphenyl)pentanoate；methyl 5-(3-hydroxyphenyl)-4-(2-methylphenyl)-5-oxopentanoate
• CAS: 170282-10-7
• 化学式: C₁₉H₂₀O₄
• 分子量: 312.365
• InChiKey: QBJGKUTUBROANX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (RS)-5-[3-(hydroxy)phenyl]-4-(2-methylphenyl)-5-oxo-pentanoate 在 sodium hydroxide 、 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (RS)-5-[3-(3-Chlorobenzyloxy)phenyl]-4-(2-methylphenyl)-5-oxopentanoic acid
  参考文献：
  名称：

  Selective endothelin A receptor antagonists. 2. Discovery and structure-activity relationships of 5-ketopentanoic acid derivatives

  摘要：

  The second in this series of papers describes the further progress made in the discovery of a potent and selective endothelin ETA receptor antagonist for the potential treatment of diseases in which endothelin has been shown to have a pathophysiological role including hypertension, ischaemic diseases and atherosclerosis. We describe herein the synthesis and structure-activity relationships of a novel series of 5-ketopentanoic acid derivatives exemplified by the lead compound 1 (IC50 0.72 mu M, rat aortic ETAR). Optimisation of the in vitro binding of 1 led to the identification of a more potent compound (37) which exhibited an IC50 < 0.1 mu M with > 300-fold selectivity for the ETA receptor over the ETB receptor. This compound demonstrated functional antagonism of endothelin-induced vasoconstriction in vitro.

  DOI：

  10.1016/s0223-5234(97)84014-7
• 作为产物：
  描述：

  3-氰基苯酚 在 palladium on activated charcoal 盐酸 、 potassium tert-butylate 、 氢气 、 碘 、 sodium hydride 、 magnesium 作用下， 以 四氢呋喃 、 甲醇 、 乙酸甲酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 methyl (RS)-5-[3-(hydroxy)phenyl]-4-(2-methylphenyl)-5-oxo-pentanoate
  参考文献：
  名称：

  Selective endothelin A receptor antagonists. 2. Discovery and structure-activity relationships of 5-ketopentanoic acid derivatives

  摘要：

  The second in this series of papers describes the further progress made in the discovery of a potent and selective endothelin ETA receptor antagonist for the potential treatment of diseases in which endothelin has been shown to have a pathophysiological role including hypertension, ischaemic diseases and atherosclerosis. We describe herein the synthesis and structure-activity relationships of a novel series of 5-ketopentanoic acid derivatives exemplified by the lead compound 1 (IC50 0.72 mu M, rat aortic ETAR). Optimisation of the in vitro binding of 1 led to the identification of a more potent compound (37) which exhibited an IC50 < 0.1 mu M with > 300-fold selectivity for the ETA receptor over the ETB receptor. This compound demonstrated functional antagonism of endothelin-induced vasoconstriction in vitro.

  DOI：

  10.1016/s0223-5234(97)84014-7

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.

  式(I)的化合物描述如下，其中R1为氢，-(较低烷基)q(CO2R6或OH)，—CN，—C(R7)HNOR8，NO2，—O(较低烷基)R9，—C≡C—R10，—CR11CH(R12)(R13)，—C(O)CH2C(O)CO2H，—CO(R14)，烷基硫醚，烷基亚砜基，烷基磺酰基，氨基甲酰基，硫代氨基甲酰基，取代的氨基甲酰基，取代的硫代氨基甲酰基，磺酰胺基或可选择取代的含氮环，m、n、o和p独立地为零或1，R2、R3、R4和R5为各种基团；以及其生理学上可接受的盐、N-氧化物和前药。这些化合物具有内皮素拮抗活性，并可用作药物。
• Selective endothelin A receptor antagonists. 2. Discovery and structure-activity relationships of 5-ketopentanoic acid derivatives
  作者：P.C. Astles、T.J. Brown、N.V. Harris、M.F. Harper、C McCarthy、B Porter、C Smith、R.J.A. Walsh

  DOI：10.1016/s0223-5234(97)84014-7

  日期：1997.6

  The second in this series of papers describes the further progress made in the discovery of a potent and selective endothelin ETA receptor antagonist for the potential treatment of diseases in which endothelin has been shown to have a pathophysiological role including hypertension, ischaemic diseases and atherosclerosis. We describe herein the synthesis and structure-activity relationships of a novel series of 5-ketopentanoic acid derivatives exemplified by the lead compound 1 (IC50 0.72 mu M, rat aortic ETAR). Optimisation of the in vitro binding of 1 led to the identification of a more potent compound (37) which exhibited an IC50 < 0.1 mu M with > 300-fold selectivity for the ETA receptor over the ETB receptor. This compound demonstrated functional antagonism of endothelin-induced vasoconstriction in vitro.