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allyl 2-{(R)-2-amino-2-[3-methyl-1,2,4-oxadiazol-5-yl]-ethylsulfanylmethyl}-3-[dimethyl(thexyl)silyloxy]-5-methoxy-6-methylbenzoate | 173152-60-8

中文名称
——
中文别名
——
英文名称
allyl 2-{(R)-2-amino-2-[3-methyl-1,2,4-oxadiazol-5-yl]-ethylsulfanylmethyl}-3-[dimethyl(thexyl)silyloxy]-5-methoxy-6-methylbenzoate
英文别名
allyl (R)-2-[2-amino-2-(3-methyl-1,2,4-oxadiazol-5-yl)ethylsulfanylmethyl]-3-[dimethyl(thexyl)silyloxy]-5-methoxy-6-methylbenzoate;(R)-2-[2-amino-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanyl-methyl]-3-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxy]-5-methoxy-6-methylbenzoic acid allyl ester;prop-2-enyl 2-[[(2R)-2-amino-2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]sulfanylmethyl]-3-[2,3-dimethylbutan-2-yl(dimethyl)silyl]oxy-5-methoxy-6-methylbenzoate
allyl 2-{(R)-2-amino-2-[3-methyl-1,2,4-oxadiazol-5-yl]-ethylsulfanylmethyl}-3-[dimethyl(thexyl)silyloxy]-5-methoxy-6-methylbenzoate化学式
CAS
173152-60-8
化学式
C26H41N3O5SSi
mdl
——
分子量
535.78
InChiKey
ZCQDOHAQGFYALS-FQEVSTJZSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

计算性质

  • 辛醇/水分配系数(LogP):
    5.99
  • 重原子数:
    36
  • 可旋转键数:
    14
  • 环数:
    2.0
  • sp3杂化的碳原子比例:
    0.58
  • 拓扑面积:
    135
  • 氢给体数:
    1
  • 氢受体数:
    9

上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量
    • 1
    • 2
    • 3

反应信息

  • 作为反应物:
    参考文献:
    名称:
    New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine
    摘要:
    Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure. From a first set of analogues, structure-activity relationships (SAR) were established for different substitution patterns, and the 14-hydroxylated, bicyclic core (X) of 1 seemed to be the structural prerequisite for DNA gyrase inhibitory activity. The variation of the lactone ring size, however, revealed that activity can be found among 11- to 16-membered lactones, and even seco-analogues were shown to maintain some enzyme inhibitory properties, thereby reducing the minimal structural requirements to a rather simple, hydroxylated benzyl sulfide (XI). On the basis of these "minimal structures" a modification program afforded a number of inhibitors that showed in vitro activity against Gram-positive bacteria. The best activities were displayed by 14-membered lactones, and representatives of this subclass exhibit excellent and broad in vitro antibacterial activity against Gram-positive pathogens, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, and overcome resistance against clinically used drugs. By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo.
    DOI:
    10.1021/jm0310232
  • 作为产物:
    参考文献:
    名称:
    New Antibacterial Agents Derived from the DNA Gyrase Inhibitor Cyclothialidine
    摘要:
    Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products. It acts by competitively inhibiting the ATPase activity exerted by the B subunit of DNA gyrase but barely exhibits any growth inhibitory activity against intact bacterial cells, presumably due to insufficient permeation of the cytoplasmic membrane. To explore the antibacterial potential of 1, we developed a flexible synthetic route allowing for the systematic modification of its structure. From a first set of analogues, structure-activity relationships (SAR) were established for different substitution patterns, and the 14-hydroxylated, bicyclic core (X) of 1 seemed to be the structural prerequisite for DNA gyrase inhibitory activity. The variation of the lactone ring size, however, revealed that activity can be found among 11- to 16-membered lactones, and even seco-analogues were shown to maintain some enzyme inhibitory properties, thereby reducing the minimal structural requirements to a rather simple, hydroxylated benzyl sulfide (XI). On the basis of these "minimal structures" a modification program afforded a number of inhibitors that showed in vitro activity against Gram-positive bacteria. The best activities were displayed by 14-membered lactones, and representatives of this subclass exhibit excellent and broad in vitro antibacterial activity against Gram-positive pathogens, including Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecalis, and overcome resistance against clinically used drugs. By improving the pharmacokinetic properties of the most active compounds (94, 97), in particular by lowering their lipophilic properties, we were able to identify congeners of cyclothialidine (1) that showed efficacy in vivo.
    DOI:
    10.1021/jm0310232
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文献信息

  • Mono- and bicyclic DNA gyrase inhibitors
    申请人:Hoffmann-La Roche Inc.
    公开号:US05589473A1
    公开(公告)日:1996-12-31
    The present invention relates to a compound of the formula ##STR1## wherein X.sup.1, R.sup.1, R.sup.2, OP, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.0 are as described herein, and their pharmaceutically acceptable salts thereof carrying an acidic and/or basic substituent. The compound of formula I as well as their pharmaceutically acceptable salts inhibit DNA gyrase activity in bacteria and possess antibiotic, especially antibacterial activity against microorganisms and can be used in the control or prevention of infectious diseases.
    本发明涉及一种具有以下结构的化合物##STR1##其中X.sup.1、R.sup.1、R.sup.2、OP、R.sup.3、R.sup.4、R.sup.5、R.sup.6和R.sup.0如本文所述,并且它们的药学上可接受的盐携带有酸性和/或碱性取代基。公式I的化合物以及它们的药学上可接受的盐抑制细菌中DNA旋转酶活性,并具有抗生素特别是抗菌活性,可用于控制或预防传染病。
  • A New DNA Gyrase Inhibitor Subclass of the Cyclothialidine Family Based on a Bicyclic Dilactam−Lactone Scaffold. Synthesis and Antibacterial Properties
    作者:Peter Angehrn、Erwin Goetschi、Hans Gmuender、Paul Hebeisen、Michael Hennig、Bernd Kuhn、Thomas Luebbers、Peter Reindl、Fabienne Ricklin、Anne Schmitt-Hoffmann
    DOI:10.1021/jm1014023
    日期:2011.4.14
    The DNA gyrase inhibitor cyclothialidine had been shown to be a valuable lead structure for the discovery of new antibacterial classes able to overcome bacterial resistance to clinically used drugs. Bicyclic lactone derivatives containing in their 12−14-membered ring a thioamide functionality were reported previously to exhibit potent antibacterial activity against Gram-positive bacteria. Moderate
    对于发现能够克服细菌对临床使用药物的耐药性的新型抗菌剂而言,DNA回旋酶抑制剂环噻啶已被证明是有价值的先导结构。先前已报道在其12-14元环中含有酰胺官能团的双环内酯衍生物对革兰氏阳性细菌表现出有效的抗菌活性。然而,仅对于带有亲性取代基的衍生物证明了中等的体内功效,发现该衍生物对药物动力学具有有利的影响,并减少了代谢降解,特别是葡萄糖醛酸化。将一个额外的酰胺单元掺入环噻啶类似物的14元单内酰胺-内酯支架中,提供了一种新的固有的极性更高的DNA促旋酶抑制剂“双内酰胺”亚类。
  • Tricyclic DNA gyrase inhibitors
    申请人:Hoffmann-La Roche Inc.
    公开号:US05594135A1
    公开(公告)日:1997-01-14
    The present invention relates to a compound of the formula ##STR1## wherein X.sup.1, R.sup.1, R.sup.2, OP, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.0 are as described herein, and their pharmaceutically acceptable salts thereof carrying an acidic and/or basic substituent. The compound of formula I as well as their pharmaceutically acceptable salts inhibit DNA gyrase activity in bacteria and possess antibiotic, especially antibacterial activity against microorganisms and can be used in the control or prevention of infectious diseases.
    本发明涉及一种化合物,其化学式为##STR1##其中X.sup.1,R.sup.1,R.sup.2,OP,R.sup.3,R.sup.4,R.sup.5,R.sup.6和R.sup.0如本说明所述,并且它们的药学上可接受的酸性和/或碱性取代物质的盐。式I化合物及其药学上可接受的盐抑制细菌中的DNA酶活性,并具有抗生素,特别是抗微生物活性,可用于控制或预防传染病。
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