tert-Butyl (((2R,4R)-4-hydroxypyrrolidin-2-yl)methyl)carbamate | 1314605-34-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-Butyl (((2R,4R)-4-hydroxypyrrolidin-2-yl)methyl)carbamate
• 英文别名: tert-butyl N-[[(2R,4R)-4-hydroxypyrrolidin-2-yl]methyl]carbamate
• CAS: 1314605-34-9
• 化学式: C₁₀H₂₀N₂O₃
• 分子量: 216.28
• InChiKey: AEEDNTYVDBGMCS-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-Butyl (((2R,4R)-4-hydroxypyrrolidin-2-yl)methyl)carbamate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三乙酰氧基硼氢化钠 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model

  摘要：

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research, heterocycle-containing tethers were explored with the intent to further improve potency and minimize hERG liabilities. This effort culminated in the discovery of compound 10, which efficiently suppressed proliferation of HCT116 and U87 cells. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration consistent with elevated and prolonged exposure in the tumor. When studied in a xenograft model, the compound demonstrated significant suppression of tumor growth. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.102

文献信息

• US5599816A
  申请人：——

  公开号：US5599816A

  公开（公告）日：1997-02-04
• US5726182A
  申请人：——

  公开号：US5726182A

  公开（公告）日：1998-03-10
• [EN] QUINOLIZINONE TYPE COMPOUNDS<br/>[FR] COMPOSES DE TYPE QUINOLIZINONE
  申请人：——

  公开号：WO1996039407A1

  公开（公告）日：1996-12-12

  [EN] Antibacterial compounds having formula (I) and the pharmaceutically acceptable salts, esters and amides thereof, selected preferred examples of which include those compounds wherein A is =CR<6>-; R<1> is cycloalkyl of from three to eight carbon atoms or substituted phenyl; R<2> is selected from the group consisting of (a), (b), (c) and (d); R<3> is halogen; R<4> is hydrogen, loweralkyl, a pharmaceutically acceptable cation, or a prodrug ester group; R<5> is hydrogen, loweralkyl, halo(loweralkyl), or -NR<13>R<14>; and R<6> is halogen, loeralkyl, halo(loweralkyl), hydroxy-substituted loweralkyl, loweralkoxy(loweralkyl), loweralkoxy, or amino(loweralkyl), as well as pharmaceutical compositions containing such compounds and the use of the same in the treatment of bacterial infections.
  [FR] L'invention se rapporte à des composés antibactériens ayant la formule (I) et à des sels pharmaceutiquement acceptables, des esters et des amides de ceux-ci, dont les exemples préférés sélectionnés comprennent ces composés et dans lesquels A représente =CR<6>-; R<1> représente cycloalkyle possédant de 3 à 8 atomes de carbone ou phényle substitué; R<2> est sélectionné dans le groupe constitué par (a), (b), (c) et (d); R<3> représente halogène; R<4> représente hydrogène, alkyle inférieur, un cation pharmaceutiquement acceptable ou un groupe ester d'un promédicament; R<5> représente hydrogène, alkyle inférieur, halo(alkyle inférieur) ou -NR<13>R<14>; et R<6> représente halogène, alkyle inférieur, halo(alkyle inférieur), alkyle inférieur substitué par hydroxy, alcoxy inférieur(alkyle inférieur), alcoxy inférieur ou amino(alkyle inférieur). L'invention se rapporte également à des compositions pharmaceutiques comprenant ces composés et à leur utilisation dans le traitement d'infections bactériennes.
• Discovery of a macrocyclic o-aminobenzamide Hsp90 inhibitor with heterocyclic tether that shows extended biomarker activity and in vivo efficacy in a mouse xenograft model
  作者：Christoph W. Zapf、Jonathan D. Bloom、Jamie L. McBean、Russell G. Dushin、Jennifer M. Golas、Hao Liu、Judy Lucas、Frank Boschelli、Erik Vogan、Jeremy I. Levin

  DOI：10.1016/j.bmcl.2011.04.102

  日期：2011.6

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research, heterocycle-containing tethers were explored with the intent to further improve potency and minimize hERG liabilities. This effort culminated in the discovery of compound 10, which efficiently suppressed proliferation of HCT116 and U87 cells. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration consistent with elevated and prolonged exposure in the tumor. When studied in a xenograft model, the compound demonstrated significant suppression of tumor growth. (C) 2011 Elsevier Ltd. All rights reserved.