O-benzyl-N-(4-butyloxycarbonyl) hydroxylamine | 5555-73-7

• 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: O-benzyl-N-(4-butyloxycarbonyl) hydroxylamine
• 英文别名: N-Benzyloxy-carbamidsaeure-butylester；butyl N-phenylmethoxycarbamate
• CAS: 5555-73-7
• 化学式: C₁₂H₁₇NO₃
• 分子量: 223.272
• InChiKey: IUMPPQHIAFFVMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 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：

  O-benzyl-N-(4-butyloxycarbonyl) hydroxylamine 在 咪唑 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、310.27 kPa 条件下， 反应 4.0h， 生成 O-(phenoxycarbonyl)-N-(4-butyloxycarbonyl) hydroxylamine
  参考文献：
  名称：

  Specificity of extended O-aryloxycarbonyl hydroxamates as inhibitors of a class C β-lactamase

  摘要：

  Class C beta-lactamases have previously been shown to be efficiently inactivated by O-aryloxycarbonyl hydroxamates. O-Phenoxycarbonyl-N-benzyloxycarbonylhydroxylamine (1) and O-phenoxycarbonyl-N-(R)-[(4-amino4- carboxy-1-butyl) oxycarbonyl] hydroxylamine (2), for example, were found to be effective inactivators. The present paper describes a structure-activity study of these molecules to better define the important structural elements for high inhibitory activity. The results show that a well-positioned hydrophobic element (which may interact with the Tyr221 residue of the enzyme) and a negatively charged element, e. g. a carboxylate group (which may interact with Arg204), are required for high reactivity with the enzyme. The new compounds were found to inactivate by forming a carbonyl cross-linked enzyme (probably Ser64OCONHLys 315) as for 1 rather than the inert hydroxamoyl derivative observed with 2.

  DOI：

  10.1016/j.bmc.2019.02.023
• 作为产物：
  描述：

  苄氧基胺盐酸盐 、 氯甲酸丁酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以52%的产率得到O-benzyl-N-(4-butyloxycarbonyl) hydroxylamine
  参考文献：
  名称：

  Specificity of extended O-aryloxycarbonyl hydroxamates as inhibitors of a class C β-lactamase

  摘要：

  Class C beta-lactamases have previously been shown to be efficiently inactivated by O-aryloxycarbonyl hydroxamates. O-Phenoxycarbonyl-N-benzyloxycarbonylhydroxylamine (1) and O-phenoxycarbonyl-N-(R)-[(4-amino4- carboxy-1-butyl) oxycarbonyl] hydroxylamine (2), for example, were found to be effective inactivators. The present paper describes a structure-activity study of these molecules to better define the important structural elements for high inhibitory activity. The results show that a well-positioned hydrophobic element (which may interact with the Tyr221 residue of the enzyme) and a negatively charged element, e. g. a carboxylate group (which may interact with Arg204), are required for high reactivity with the enzyme. The new compounds were found to inactivate by forming a carbonyl cross-linked enzyme (probably Ser64OCONHLys 315) as for 1 rather than the inert hydroxamoyl derivative observed with 2.

  DOI：

  10.1016/j.bmc.2019.02.023

文献信息

• Methods for lowering blood cholesterol
  申请人：BERGER FRANK M

  公开号：US03245878A1

  公开（公告）日：1966-04-12
• The Synthesis of Hydroxylamine Derivatives Possessing Hypocholesteremic Activity
  作者：B. J. Ludwig、F. Dursch、M. Auerbach、K. Tomeczek、F. M. Berger

  DOI：10.1021/jm00316a012

  日期：1967.7
• ACYLATED OLIGOPEPTIDE DERIVATIVES HAVING CELL SIGNAL INHIBITING ACTIVITY
  申请人：Novartis AG

  公开号：EP0846127A1

  公开（公告）日：1998-06-10
• US6310095B1
  申请人：——

  公开号：US6310095B1

  公开（公告）日：2001-10-30
• [EN] ACYLATED OLIGOPEPTIDE DERIVATIVES HAVING CELL SIGNAL INHIBITING ACTIVITY<br/>[FR] DERIVES OLIGOPEPTIDIQUES ACYLES PRESENTANT UNE ACTIVITE INHIBANT DES SIGNAUX CELLULAIRES
  申请人：NOVARTIS AG

  公开号：WO1997008193A1

  公开（公告）日：1997-03-06

  (EN) The invention relates to an acylated peptide, namely a compound of formula (I), wherein n is 0 to 15, X is arylcarbonyl, cycloalkylcarbonyl, tricycloalkylcarbonyl, arylsulfonyl, heterocyclylcarbonyl, heterocyclylsulfonyl, carbamoyl-lower alkanoyl, aryl-lower alkylcarbonyl, cycloalkyl-lower alkylcarbonyl, aryl-lower alkylsulfonyl, heterocyclyl-lower alkylcarbonyl, heterocyclyl-lower alkylsulfonyl with the proviso that in any of the lower alkyl radicals mentioned a methylene group may be replaced with oxa, aza or thia; heterocyclyl-lower alkenylcarbonyl or aryl-lower alkenylcarbonyl; or, if Y is a secondary or tertiary amino group, is one of the moieties X mentioned above or lower alkanoyl, halo-lower alkanoyl, lower-alkoxycarbonyl, aryl-lower alkoxycarbonyl or cycloalkyl-lower alkoxycarbonyl; PTI is the bivalent radical of tyrosine or (preferably) the bivalent radical of phosphotyrosine or a phosphotyrosine mimic, AA stands for a bivalent radical of a natural or unnatural amino acid, and Y is hydroxy, a C-terminal protecting group or a primary, secondary or tertiary amino group, or a salt thereof, said compound being useful for the treatment of diseases that respond to inhibition of the interaction of (a) protein(s) comprising (an) SH2 domain(s) and a protein tyrosine kinase or a modified version thereof.(FR) L'invention concerne un peptide acylé, en l'occurrence un composé de formule (I). Dans cette formule, n est compris entre 0 et 15; X est un arylcarbonyle, cycloalkylcarbonyle, tricycloalkylcarbonyle, arylsulfonyle, hétérocyclylcarbonyle, hétérocyclylsulfonyle, carbamoyl(alcanoyle inférieur), aryl(alkyle inférieur)carbonyle, cycloalkyl(alkyle inférieur)carbonyle, aryl(alkyle inférieur)sulfonyle, hétérocyclyl(alkyle inférieur)carbonyle, hétérocyclyl(alkyle inférieur)sulfonyle, à condition qu'un groupe méthylène de l'un quelconque de ces radicaux alkyle inférieur puisse être remplacé par oxa, aza ou thia; hétérocyclyl(alcényle inférieur)carbonyle ou aryl(alcényle inférieur)carbonyle; ou, si Y est un groupe amine secondaire ou tertiaire, une fractions X ci-dessus, ou un alcanoyle inférieur, halo(alcanoyle inférieur), (alcoxy inférieur)carbonyle, aryl(alcoxy inférieur)carbonyle ou cycloalkyl(alcoxy inférieur)carbonyle; PTI est le radical bivalent de la tyrosine, ou de préférence de la phosphotyrosine ou encore d'une substance mimétique de la phosphotyrosine, AA est un radical bivalent d'un acide aminé naturel ou synthétique et Y est un hydroxy, un groupe protégeant l'extrémité C-terminale ou un groupe amine primaire, secondaire ou tertiaire. L'invention concerne également les sels dudit peptide. Ce composé et ses sels sont utiles pour traiter des maladies réagissant à l'inhibition de l'interaction entre une ou des protéines comprenant un ou des domaines SH2, et une protéine tyrosine kinase, ou une version modifiée d'une telle kinase.