(1SR,2SR)-2-(tert-butoxy)cyclopropanecarboxylic acid | 108106-42-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1SR,2SR)-2-(tert-butoxy)cyclopropanecarboxylic acid
• 英文别名: (+/-)-trans-2-tert-butoxy-cyclopropanecarboxylic acid；(+/-)-trans-2-tert-Butoxy-cyclopropancarbonsaeure；rac-(1R,2R)-2-(tert-butoxy)cyclopropane-1-carboxylic acid, trans；(1R,2R)-2-[(2-methylpropan-2-yl)oxy]cyclopropane-1-carboxylic acid
• CAS: 108106-42-9
• 化学式: C₈H₁₄O₃
• 分子量: 158.197
• InChiKey: DDPPJEZOTLIJIK-PHDIDXHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1SR,2SR)-2-(tert-butoxy)cyclopropanecarboxylic acid 在 N-羟基-7-氮杂苯并三氮唑 、 palladium 10% on activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-((3R,4S,5S)-5-(4-amino-3-fluoro-5-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)benzyl)-4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran-3-yl)-((1RS,2SR)-2-(tert-butoxy)cyclopropanecarboxamide)
  参考文献：
  名称：

  Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides

  摘要：

  Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APPS1/16 transgenic mice at oral doses of 180 mu mol/kg demonstrated significant reduction of brain A beta levels.

  DOI：

  10.1021/jm300069y
• 作为产物：
  描述：

  叔丁基乙烯基醚 在 氢氧化钾 、 copper(II) sulfate 作用下， 生成 (1SR,2SR)-2-(tert-butoxy)cyclopropanecarboxylic acid
  参考文献：
  名称：

  住院时间和手术程序的使用是决定心力衰竭医院费用的主要因素。

  摘要：

  背景技术在该国家，每年在心力衰竭（HF）管理上花费的100亿美元中的大部分归因于医院收费。为防止这种疾病的发生，人们进行了广泛的努力，以减少住院费用和缩短住院时间（LOS），从而降低治疗费用。假设本研究的目的是确定在众多不同患者中急性心衰的住院费用的主要决定因素。方法获得有关所有1995年纽约州医院出院分配的ICD-9-CM编码的管理信息，这些编码指示主要诊断位置为HF。利用双变量和多变量统计分析来确定对医院收费影响最大的那些特定于患者和医院的特征。结果总计43 确定了157例患者。平均住院费用为$ 11,507 +/- 15,995，平均住院日为9.6 +/- 14.5天。通过多变量分析，医院费用增加的最重要的独立预测因素是：LOS更长，入读教学医院，在重症监护室进行治疗以及心脏手术，永久性起搏器和机械通气的利用。年龄，性别，种族，合并症评分和医疗保险，以及心脏病专家的治疗以及指数住院期

  DOI：

  10.1002/clc.4960240110

文献信息

• Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides
  作者：Heinrich Rueeger、Rainer Lueoend、Olivier Rogel、Jean-Michel Rondeau、Henrik Möbitz、Rainer Machauer、Laura Jacobson、Matthias Staufenbiel、Sandrine Desrayaud、Ulf Neumann

  DOI：10.1021/jm300069y

  日期：2012.4.12

  Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a central core template without any amide functionality. The core scaffold selection and the structure activity relationship development were supported by molecular modeling studies and by X-ray analysis of BACE1 complexes with various ligands to expedite the optimization of the series. The direct extension from P1-aryl- and heteroaryl moieties into the S3 binding pocket allowed the enhancement of potency and selectivity over cathepsin D. Restraining the design and synthesis of compounds to a physicochemical property space consistent with central nervous system drugs led to inhibitors with improved blood brain barrier permeability. Guided by structure-based optimization, we were able to obtain highly potent compounds such as 60p with enzymatic and cellular IC50 values of 2 and 50 nM, respectively, and with >200-fold selectivity over cathepsin D. Pharmacodynamic studies in APPS1/16 transgenic mice at oral doses of 180 mu mol/kg demonstrated significant reduction of brain A beta levels.
• Length of stay and procedure utilization are the major determinants of hospital charges for heart failure
  作者：Edward F. Philbin、Peter A. Mccullough、G William Dec、Thomas G. Disalvo

  DOI：10.1002/clc.4960240110

  日期：2001.1

  billion dollars spent annually on heart failure (HF) management in this country is attributed to hospital charges. There are widespread efforts to decrease the costs of treating this disorder, both by preventing hospital admissions and reducing lengths of stay (LOS). HYPOTHESIS The objective of this study was to identify the major determinants of hospital charges for an acute hospitalization for HF

  背景技术在该国家，每年在心力衰竭（HF）管理上花费的100亿美元中的大部分归因于医院收费。为防止这种疾病的发生，人们进行了广泛的努力，以减少住院费用和缩短住院时间（LOS），从而降低治疗费用。假设本研究的目的是确定在众多不同患者中急性心衰的住院费用的主要决定因素。方法获得有关所有1995年纽约州医院出院分配的ICD-9-CM编码的管理信息，这些编码指示主要诊断位置为HF。利用双变量和多变量统计分析来确定对医院收费影响最大的那些特定于患者和医院的特征。结果总计43 确定了157例患者。平均住院费用为$ 11,507 +/- 15,995，平均住院日为9.6 +/- 14.5天。通过多变量分析，医院费用增加的最重要的独立预测因素是：LOS更长，入读教学医院，在重症监护室进行治疗以及心脏手术，永久性起搏器和机械通气的利用。年龄，性别，种族，合并症评分和医疗保险，以及心脏病专家的治疗以及指数住院期