(3S,6R)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-(2-thiophen-2-yl-acetylamino)-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate | 1681053-97-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (3S,6R)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-(2-thiophen-2-yl-acetylamino)-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate
• 英文别名: 4,6-Methano-1,3,2-benzodioxaborole-2-hexanoic acid, I(2)-[[(1,1-dimethylethyl)dimethylsilyl]oxy]hexahydro-3a,5,5-trimethyl-Imicro-[[2-(2-thienyl)acetyl]amino]-, 1,1-dimethylethyl ester, (I(2)S,ImicroR,3aS,4S,6S,7aR)-；tert-butyl (3S,6R)-3-[tert-butyl(dimethyl)silyl]oxy-6-[(2-thiophen-2-ylacetyl)amino]-6-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexanoate
• CAS: 1681053-97-3
• 化学式: C₃₂H₅₄BNO₆SSi
• 分子量: 619.746
• InChiKey: IOKITOZSESQFRB-WWZRZJFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.95
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,6R)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-(2-thiophen-2-yl-acetylamino)-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate 以64的产率得到法硼巴坦
  参考文献：
  名称：

  J. Med. Chem. 2015, 58, 3682-3692

  摘要：

  DOI：
• 作为产物：
  描述：

  2-噻吩乙酸 、 在 lithium hexamethyldisilazane 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N-甲基吗啉 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.5h， 生成 (3S,6R)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-(2-thiophen-2-yl-acetylamino)-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate
  参考文献：
  名称：

  Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases

  摘要：

  The increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the beta-lactam class of antimicrobials. A program was initiated to discover a new series of serine beta-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine beta-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria.

  DOI：

  10.1021/acs.jmedchem.5b00127

文献信息

• Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases
  作者：Scott J. Hecker、K. Raja Reddy、Maxim Totrov、Gavin C. Hirst、Olga Lomovskaya、David C. Griffith、Paula King、Ruslan Tsivkovski、Dongxu Sun、Mojgan Sabet、Ziad Tarazi、Matthew C. Clifton、Kateri Atkins、Amy Raymond、Kristy T. Potts、Jan Abendroth、Serge H. Boyer、Jeffrey S. Loutit、Elizabeth E. Morgan、Stephanie Durso、Michael N. Dudley

  DOI：10.1021/acs.jmedchem.5b00127

  日期：2015.5.14

  The increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the beta-lactam class of antimicrobials. A program was initiated to discover a new series of serine beta-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine beta-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria.
• J. Med. Chem. 2015, 58, 3682-3692
  作者：

  DOI：——

  日期：——