1-[羟基(苯基)甲基]环己烷-1-羧酸 | 90962-78-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 中文名称: 1-[羟基(苯基)甲基]环己烷-1-羧酸
• 英文名称: 1-[Hydroxy(phenyl)methyl]cyclohexane-1-carboxylic acid
• CAS: 90962-78-0
• 化学式: C₁₄H₁₈O₃
• 分子量: 234.295
• InChiKey: RFGPONBBEZEXMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[羟基(苯基)甲基]环己烷-1-羧酸 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 甲苯 为溶剂， 生成
  参考文献：
  名称：

  The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir®: A change in direction in the search for a second generation HCV NS3 protease inhibitor

  摘要：

  In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir (R) 1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tertbutyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.063
• 作为产物：
  描述：

  methyl 1-[hydroxy(phenyl)methyl]cyclohexanecarboxylate 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 生成 1-[羟基(苯基)甲基]环己烷-1-羧酸
  参考文献：
  名称：

  The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir®: A change in direction in the search for a second generation HCV NS3 protease inhibitor

  摘要：

  In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir (R) 1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tertbutyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.063

文献信息

• Ketene bis(trimethylsilyl) acetals. Cross-aldol type condensation reactions with aldehydes and schiff bases
  作者：Jacques-Emile Dubois、Georges Axiotis

  DOI：10.1016/s0040-4039(01)81183-7

  日期：1984.1

  Condensation of the title acetals with aldehydes and Schiff bases in the presence of titanium tetrachloride is reported for the first time. It leads to β-hydroxyacids and to β-lactams via a cross-aldol type reaction, with good yields.

  首次报道了标题缩醛在四氯化钛存在下与醛和席夫碱的缩合。它通过交叉羟醛型反应生成β-羟酸和β-内酰胺，收率很好。
• DUBOIS, J. -E.;AXIOTIS, G., TETRAHEDRON LETT., 1984, 25, N 20, 2143-2146
  作者：DUBOIS, J. -E.、AXIOTIS, G.

  DOI：——

  日期：——
• The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir®: A change in direction in the search for a second generation HCV NS3 protease inhibitor
  作者：Frank Bennett、Yuhua Huang、Siska Hendrata、Raymond Lovey、Stephane L. Bogen、Weidong Pan、Zhuyan Guo、Andrew Prongay、Kevin X. Chen、Ashok Arasappan、Srikanth Venkatraman、Francisco Velazquez、Latha Nair、Mousumi Sannigrahi、Xiao Tong、John Pichardo、Kuo-Chi Cheng、Viyyoor M. Girijavallabhan、Anil K. Saksena、F. George Njoroge

  DOI：10.1016/j.bmcl.2010.02.063

  日期：2010.4

  In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir (R) 1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tertbutyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. (C) 2010 Elsevier Ltd. All rights reserved.