(R)-tert-butyl 3-hydroxypropane-1,2-diyldicarbamate | 325140-39-4

• 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: (R)-tert-butyl 3-hydroxypropane-1,2-diyldicarbamate
• 英文别名: tert-butyl N-[(2R)-1-{[(tert-butoxy)carbonyl]amino}-3-hydroxypropan-2-yl]carbamate；tert-butyl N-[(2R)-1-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]carbamate
• CAS: 325140-39-4
• 化学式: C₁₃H₂₆N₂O₅
• 分子量: 290.36
• InChiKey: HJLRHPPPZYAKFG-SECBINFHSA-N

物化性质

• 沸点：
  448.6±40.0 °C(Predicted)
• 密度：
  1.092±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  96.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 3-hydroxypropane-1,2-diyldicarbamate 在 咪唑 、 碘 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到(R)-tert-butyl 3-iodopropane-1,2-diyldicarbamate
  参考文献：
  名称：

  Structure−Activity Relationships in Toll-like Receptor-2 Agonistic Diacylthioglycerol Lipopeptides

  摘要：

  The N-termini of bacterial lipoproteins are acylated with a (S)-(2,3-bisacyloxypropyl)cysteinyl residue. Lipopeptides derived from lipoproteins activate innate immune responses by engaging Toll-like receptor 2 (TLR2) and are highly immunostimulatory and yet without apparent toxicity in animal models. The lipopeptides may therefore be useful as potential immunotherapeutic agents. Previous structure activity relationships in such lipopeptides have largely been obtained using murine cells, and it is now clear that significant species-specific differences exist between human and murine TLR responses. We have examined in detail the role of the highly conserved Cys residue as well as the geometry and stereochemistry of the Cys-Ser dipeptide unit. (R)-Diacylthioglycerol analogues are maximally active in reporter gene assays using human TLR2. The Cys-Ser dipeptide unit represents the minimal part-structure, but its stereochemistry was found not to be a critical determinant of activity. The thioether bridge between the diacyl and dipeptide units is crucial, and replacement by an oxoether bridge results in a dramatic decrease in activity.

  DOI：

  10.1021/jm901839g
• 作为产物：
  描述：

  (R)-methyl 2,2,1,11-tetramethyl-4,9-dioxo-3,10-dioxa-5,8-diazadodecane-6-carboxylate 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 以96%的产率得到(R)-tert-butyl 3-hydroxypropane-1,2-diyldicarbamate
  参考文献：
  名称：

  Structure−Activity Relationships in Toll-like Receptor-2 Agonistic Diacylthioglycerol Lipopeptides

  摘要：

  The N-termini of bacterial lipoproteins are acylated with a (S)-(2,3-bisacyloxypropyl)cysteinyl residue. Lipopeptides derived from lipoproteins activate innate immune responses by engaging Toll-like receptor 2 (TLR2) and are highly immunostimulatory and yet without apparent toxicity in animal models. The lipopeptides may therefore be useful as potential immunotherapeutic agents. Previous structure activity relationships in such lipopeptides have largely been obtained using murine cells, and it is now clear that significant species-specific differences exist between human and murine TLR responses. We have examined in detail the role of the highly conserved Cys residue as well as the geometry and stereochemistry of the Cys-Ser dipeptide unit. (R)-Diacylthioglycerol analogues are maximally active in reporter gene assays using human TLR2. The Cys-Ser dipeptide unit represents the minimal part-structure, but its stereochemistry was found not to be a critical determinant of activity. The thioether bridge between the diacyl and dipeptide units is crucial, and replacement by an oxoether bridge results in a dramatic decrease in activity.

  DOI：

  10.1021/jm901839g

文献信息

• METALLO-BETA-LACTAMASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP3313828A1

  公开（公告）日：2018-05-02
• [EN] METALLO-BETA-LACTAMASE INHIBITORS<br/>[FR] INHIBITEURS DE MÉTALLO-BÊTA-LACTAMASES
  申请人：MERCK SHARP & DOHME

  公开号：WO2016210234A1

  公开（公告）日：2016-12-29

  The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: (I) and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and RB are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt therof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.