4-(3-羟基苯基)-2-戊酮 | 899797-71-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 4-(3-羟基苯基)-2-戊酮
• 英文名称: 4-(3-hydroxyphenyl)pentan-2-one
• 英文别名: 4-(3-Hydroxyphenyl)pentan-2-one
• CAS: 899797-71-8
• 化学式: C₁₁H₁₄O₂
• 分子量: 178.231
• InChiKey: QWLBJZFRZYLJOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3-羟基苯基)-2-戊酮 在 盐酸 、 三乙基硅烷 、 sodium hydride 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 2-[2,4-dichloro-3-(2,4-dimethylquinolin-8-yloxymethyl)benzenesulfonylamino]-2-methylpropionic acid
  参考文献：
  名称：

  Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 1. Synthesis and SAR of α,α-Dimethylglycine Sulfonamides

  摘要：

  We recently published the extensive in vivo pharmacological characterization of MEN 16132 (J. Pharmacol. Exp. Ther. 2005, 616- 623; Eur. J. Pharmacol. 2005, 528, 7), a member of the sulfonamide-containing human B-2 receptor (hB(2)R) antagonists. Here we report, in detail, how this family of compounds was designed, synthesized, and optimized to provide a group of products with subnanomolar affinity for the hB2R and high in vivo potency after topical administration to the respiratory tract. The series was designed on the basis of indications from the X-ray structures of the key structural motifs A and B present in known antagonists and is characterized by the presence of an alpha,alpha-dialkyl amino acid. The first lead ( 17) of the series was submitted to extensive chemical work to elucidate the structural requirements to increase hB(2) receptor affinity and antagonist potency in bioassays expressing the human B2 receptor ( hB2R). The following structural features were selected: a 2,4-dimethylquinoline moiety and a piperazine linker acylated with a basic amino acid. The representative lead compound 68 inhibited the specific binding of [H-3] BK to hB(2)R with a pKi of 9.4 and antagonized the BK-induced inositolphosphate (IP) accumulation in recombinant cell systems expressing the hB(2)R with a pA(2) of 9.1. Moreover, compound 68 when administered (300 nmol/kg) intratracheally in the anesthetized guinea pig, was able to significantly inhibit BK-induced bronchoconstriction for up to 120 min after its administration, while having a lower and shorter lasting effect on hypotension.

  DOI：

  10.1021/jm060137l
• 作为产物：
  描述：

  间羟基苯甲醛 在 sodium hydroxide 、 copper(l) chloride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 3.0h， 生成 4-(3-羟基苯基)-2-戊酮
  参考文献：
  名称：

  Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 1. Synthesis and SAR of α,α-Dimethylglycine Sulfonamides

  摘要：

  We recently published the extensive in vivo pharmacological characterization of MEN 16132 (J. Pharmacol. Exp. Ther. 2005, 616- 623; Eur. J. Pharmacol. 2005, 528, 7), a member of the sulfonamide-containing human B-2 receptor (hB(2)R) antagonists. Here we report, in detail, how this family of compounds was designed, synthesized, and optimized to provide a group of products with subnanomolar affinity for the hB2R and high in vivo potency after topical administration to the respiratory tract. The series was designed on the basis of indications from the X-ray structures of the key structural motifs A and B present in known antagonists and is characterized by the presence of an alpha,alpha-dialkyl amino acid. The first lead ( 17) of the series was submitted to extensive chemical work to elucidate the structural requirements to increase hB(2) receptor affinity and antagonist potency in bioassays expressing the human B2 receptor ( hB2R). The following structural features were selected: a 2,4-dimethylquinoline moiety and a piperazine linker acylated with a basic amino acid. The representative lead compound 68 inhibited the specific binding of [H-3] BK to hB(2)R with a pKi of 9.4 and antagonized the BK-induced inositolphosphate (IP) accumulation in recombinant cell systems expressing the hB(2)R with a pA(2) of 9.1. Moreover, compound 68 when administered (300 nmol/kg) intratracheally in the anesthetized guinea pig, was able to significantly inhibit BK-induced bronchoconstriction for up to 120 min after its administration, while having a lower and shorter lasting effect on hypotension.

  DOI：

  10.1021/jm060137l

文献信息

• J. Med. Chem. 2007, 50, 550-565
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 2006, 49, 3602-3613
  作者：

  DOI：——

  日期：——
• Design and Synthesis of Novel Sulfonamide-Containing Bradykinin hB₂ Receptor Antagonists. 1. Synthesis and SAR of α,α-Dimethylglycine Sulfonamides
  作者：Daniela Fattori、Cristina Rossi、Christopher I. Fincham、Marco Berettoni、Federico Calvani、Fernando Catrambone、Patrizia Felicetti、Martina Gensini、Rosa Terracciano、Maria Altamura、Alessandro Bressan、Sandro Giuliani、Carlo A. Maggi、Stefania Meini、Claudio Valenti、Laura Quartara

  DOI：10.1021/jm060137l

  日期：2006.6.1

  We recently published the extensive in vivo pharmacological characterization of MEN 16132 (J. Pharmacol. Exp. Ther. 2005, 616- 623; Eur. J. Pharmacol. 2005, 528, 7), a member of the sulfonamide-containing human B-2 receptor (hB(2)R) antagonists. Here we report, in detail, how this family of compounds was designed, synthesized, and optimized to provide a group of products with subnanomolar affinity for the hB2R and high in vivo potency after topical administration to the respiratory tract. The series was designed on the basis of indications from the X-ray structures of the key structural motifs A and B present in known antagonists and is characterized by the presence of an alpha,alpha-dialkyl amino acid. The first lead ( 17) of the series was submitted to extensive chemical work to elucidate the structural requirements to increase hB(2) receptor affinity and antagonist potency in bioassays expressing the human B2 receptor ( hB2R). The following structural features were selected: a 2,4-dimethylquinoline moiety and a piperazine linker acylated with a basic amino acid. The representative lead compound 68 inhibited the specific binding of [H-3] BK to hB(2)R with a pKi of 9.4 and antagonized the BK-induced inositolphosphate (IP) accumulation in recombinant cell systems expressing the hB(2)R with a pA(2) of 9.1. Moreover, compound 68 when administered (300 nmol/kg) intratracheally in the anesthetized guinea pig, was able to significantly inhibit BK-induced bronchoconstriction for up to 120 min after its administration, while having a lower and shorter lasting effect on hypotension.