benzyl {1-[{[tert-butyl(dimethyl)silyl]oxy}(3-chlorophenyl)methyl]prop-2-en-1-yl}carbamate | 1190391-52-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl {1-[{[tert-butyl(dimethyl)silyl]oxy}(3-chlorophenyl)methyl]prop-2-en-1-yl}carbamate
• 英文别名: benzyl N-[(1R,2S)-1-[tert-butyl(dimethyl)silyl]oxy-1-(3-chlorophenyl)but-3-en-2-yl]carbamate
• CAS: 1190391-52-6
• 化学式: C₂₄H₃₂ClNO₃Si
• 分子量: 446.061
• InChiKey: DSKWGHFWNWHAAU-FCHUYYIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.88
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl N-[4-(2-oxobut-3-enyl)phenyl]carbamate 、 benzyl {1-[{[tert-butyl(dimethyl)silyl]oxy}(3-chlorophenyl)methyl]prop-2-en-1-yl}carbamate 在 Zhan I catalyst 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Design of a novel pyrrolidine scaffold utilized in the discovery of potent and selective human β3 adrenergic receptor agonists

  摘要：

  A novel class of human beta(3)-adrenergic receptor agonists was designed in effort to improve selectivity and metabolic stability versus previous disclosed beta(3)-AR agonists. As observed, many of the beta(3)-AR agonists seem to need the acyclic ethanolamine core for agonist activity. We have synthesized derivatives that constrained this moiety by introduction of a pyrrolidine. This unique modification maintains human beta(3) functional potency with improved selectivity versus ancillary targets and also eliminates the possibility of the same oxidative metabolites formed from cleavage of the N-C bond of the ethanolamine. Compound 39 exhibited excellent functional beta(3) agonist potency across species with good pharmacokinetic properties in rat, dog, and rhesus monkeys. Early de-risking of this novel pyrrolidine core (44) via full AMES study supports further research into various new beta(3)-AR agonists containing the pyrrolidine moiety. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.087
• 作为产物：
  描述：

  1-(3-chlorophenyl)prop-2-en-1-ol 在 咪唑 、 盐酸 、 臭氧 、 copper(II) sulfate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 benzyl {1-[{[tert-butyl(dimethyl)silyl]oxy}(3-chlorophenyl)methyl]prop-2-en-1-yl}carbamate
  参考文献：
  名称：

  Design of a novel pyrrolidine scaffold utilized in the discovery of potent and selective human β3 adrenergic receptor agonists

  摘要：

  A novel class of human beta(3)-adrenergic receptor agonists was designed in effort to improve selectivity and metabolic stability versus previous disclosed beta(3)-AR agonists. As observed, many of the beta(3)-AR agonists seem to need the acyclic ethanolamine core for agonist activity. We have synthesized derivatives that constrained this moiety by introduction of a pyrrolidine. This unique modification maintains human beta(3) functional potency with improved selectivity versus ancillary targets and also eliminates the possibility of the same oxidative metabolites formed from cleavage of the N-C bond of the ethanolamine. Compound 39 exhibited excellent functional beta(3) agonist potency across species with good pharmacokinetic properties in rat, dog, and rhesus monkeys. Early de-risking of this novel pyrrolidine core (44) via full AMES study supports further research into various new beta(3)-AR agonists containing the pyrrolidine moiety. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.087

文献信息

• Design of a novel pyrrolidine scaffold utilized in the discovery of potent and selective human β3 adrenergic receptor agonists
  作者：Gregori J. Morriello、Harvey R. Wendt、Alka Bansal、Jerry Di Salvo、Scott Feighner、Jiafang He、Amanda L. Hurley、Donna L. Hreniuk、Gino M. Salituro、Marat Vijay Reddy、Sheila M. Galloway、Katherine K. McGettigan、George Laws、Crystal McKnight、George A. Doss、Nancy N. Tsou、Regina M. Black、Judy Morris、Richard G. Ball、Anthony T. Sanfiz、Eric Streckfuss、Mary Struthers、Scott D. Edmondson

  DOI：10.1016/j.bmcl.2010.12.087

  日期：2011.3

  A novel class of human beta(3)-adrenergic receptor agonists was designed in effort to improve selectivity and metabolic stability versus previous disclosed beta(3)-AR agonists. As observed, many of the beta(3)-AR agonists seem to need the acyclic ethanolamine core for agonist activity. We have synthesized derivatives that constrained this moiety by introduction of a pyrrolidine. This unique modification maintains human beta(3) functional potency with improved selectivity versus ancillary targets and also eliminates the possibility of the same oxidative metabolites formed from cleavage of the N-C bond of the ethanolamine. Compound 39 exhibited excellent functional beta(3) agonist potency across species with good pharmacokinetic properties in rat, dog, and rhesus monkeys. Early de-risking of this novel pyrrolidine core (44) via full AMES study supports further research into various new beta(3)-AR agonists containing the pyrrolidine moiety. (C) 2011 Elsevier Ltd. All rights reserved.