tert-butyl ((2R,3R)-2-((tert-butyldimethylsilyl)oxy)-4-(isopropylamino)-3-methylbutyl)(methyl)carbamate | 1393801-86-9

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: tert-butyl ((2R,3R)-2-((tert-butyldimethylsilyl)oxy)-4-(isopropylamino)-3-methylbutyl)(methyl)carbamate
• 英文别名: tert-butyl N-[(2R,3R)-2-[tert-butyl(dimethyl)silyl]oxy-3-methyl-4-(propan-2-ylamino)butyl]-N-methylcarbamate
• CAS: 1393801-86-9
• 化学式: C₂₀H₄₄N₂O₃Si
• 分子量: 388.666
• InChiKey: CTMQGHPZRBHAFQ-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.88
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl ((2R,3R)-2-((tert-butyldimethylsilyl)oxy)-4-(isopropylamino)-3-methylbutyl)(methyl)carbamate 在 Hoveyda-Grubbs catalyst second generation 、 四丁基氟化铵 、 氢气 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 palladium(II) hydroxide 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 108.0h， 生成 1-(3,5-dimethylisoxazol-4-yl)-3-((2S,8R,9R)-11-isopropyl-2,9-dimethyl-8-((methylamino)methyl)-12-oxo-2,3,4,5,6,8,9,10,11,12-decahydrobenzo[b][1,9,5]dioxaazacyclotetradecin-14-yl)urea
  参考文献：
  名称：

  Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents

  摘要：

  Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.

  DOI：

  10.1021/jm500994n
• 作为产物：
  描述：

  (2S,3R)-4-(tert-butoxycarbonyl(methyl)amino)-3-(tert-butyldimethylsilyloxy)-2-methylbutanoic acid 在 dimethyl sulfide borane 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 tert-butyl ((2R,3R)-2-((tert-butyldimethylsilyl)oxy)-4-(isopropylamino)-3-methylbutyl)(methyl)carbamate
  参考文献：
  名称：

  [EN] SMALL MOLECULE INHIBITORS FOR TREATING PARASITIC INFECTIONS
  [FR] INHIBITEURS À PETITES MOLÉCULES UTILISABLES EN VUE DU TRAITEMENT D'INFECTIONS PARASITAIRES

  摘要：

  本发明涉及公式I化合物或其药学上可接受的酯、盐、前药或代谢物。

  公开号：

  WO2012112568A1

文献信息

• [EN] SMALL MOLECULE INHIBITORS FOR TREATING PARASITIC INFECTIONS<br/>[FR] INHIBITEURS À PETITES MOLÉCULES UTILISABLES EN VUE DU TRAITEMENT D'INFECTIONS PARASITAIRES
  申请人：BROAD INST INC

  公开号：WO2012112568A1

  公开（公告）日：2012-08-23

  The invention relates to a compound of Formula I or a pharmaceutically acceptable ester, salt, prodrug or metabolite thereof;

  本发明涉及公式I化合物或其药学上可接受的酯、盐、前药或代谢物。
• SMALL MOLECULE INHIBITORS FOR TREATING PARASITIC INFECTIONS
  申请人：NEW YORK UNIVERSITY

  公开号：US20140045860A1

  公开（公告）日：2014-02-13

  The invention relates to a compound of Formula I or a pharmaceutically acceptable ester, salt, prodrug or metabolite thereof;

  该发明涉及化合物I的制备或其药学上可接受的酯、盐、前药或代谢物。
• Diversity-Oriented Synthesis-Facilitated Medicinal Chemistry: Toward the Development of Novel Antimalarial Agents
  作者：Eamon Comer、Jennifer A. Beaudoin、Nobutaka Kato、Mark E. Fitzgerald、Richard W. Heidebrecht、Maurice duPont Lee、Daniela Masi、Marion Mercier、Carol Mulrooney、Giovanni Muncipinto、Ann Rowley、Keila Crespo-Llado、Adelfa E. Serrano、Amanda K. Lukens、Roger C. Wiegand、Dyann F. Wirth、Michelle A. Palmer、Michael A. Foley、Benito Munoz、Christina A. Scherer、Jeremy R. Duvall、Stuart L. Schreiber

  DOI：10.1021/jm500994n

  日期：2014.10.23

  Here, we describe medicinal chemistry that was accelerated by a diversity-oriented synthesis (DOS) pathway, and in vivo studies of our previously reported macrocyclic antimalarial agent that derived from the synthetic pathway. Structure-activity relationships that focused on both appendage and skeletal features yielded a nanomolar inhibitor of P. falciparum asexual blood-stage growth with improved solubility and microsomal stability and reduced hERG binding. The build/couple/pair (B/C/P) synthetic strategy, used in the preparation of the original screening library, facilitated medicinal chemistry optimization of the antimalarial lead.