Mono<butyl> bis<butyl> isocyanurate | 153756-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: Mono<butyl> bis<butyl> isocyanurate
• 英文别名: 4-[4-[3,5-Bis[4-[acetyl(phenylmethoxy)amino]butyl]-2,4,6-trioxo-1,3,5-triazinan-1-yl]butyl-phenylmethoxyamino]-4-oxobutanoic acid
• CAS: 153756-41-3
• 化学式: C₄₄H₅₆N₆O₁₁
• 分子量: 844.962
• InChiKey: JQARKPCKTRQISR-UHFFFAOYSA-N

物化性质

• 沸点：
  920.3±75.0 °C(predicted)
• 密度：
  1.258±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  61
• 可旋转键数：
  27
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  187
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  Mono<butyl> bis<butyl> isocyanurate 在 palladium on activated charcoal 盐酸 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 生成 Mono<succinyl>-N-hydroxyamino>butyl> bis<(N-acetyl-N-hydroxyamino)butyl> isocyanurate
  参考文献：
  名称：

  Iron Transport-Mediated Drug Delivery: Synthesis and Biological Evaluation of Cyanuric Acid-Based Siderophore Analogs and .beta.-Lactam Conjugates

  摘要：

  Trihydroxamate-containing isocyanurates 4a-c were synthesized and determined to be capable of substituting for natural siderophores (microbial iron sequestering agents) in limited microbiological assays. The direct coupling of protected 4a to carbacephalosporins 16 and 17 and subsequent deprotection gave conjugates 20 and 21. The Lorabid conjugate 21 was especially active against E. coli X580 in preliminary biological tests, thus demonstrating the continued potential of siderophore-mediated drug delivery.

  DOI：

  10.1021/jo00084a018
• 作为产物：
  描述：

  丁二酸酐 、 Mono<-N-(benzyloxy)amino>butyl>bis<butyl> isocyanurate 在 溶剂黄146 、 锌 作用下， 以 四氢呋喃 为溶剂， 以99%的产率得到Mono<butyl> bis<butyl> isocyanurate
  参考文献：
  名称：

  Iron Transport-Mediated Drug Delivery: Synthesis and Biological Evaluation of Cyanuric Acid-Based Siderophore Analogs and .beta.-Lactam Conjugates

  摘要：

  Trihydroxamate-containing isocyanurates 4a-c were synthesized and determined to be capable of substituting for natural siderophores (microbial iron sequestering agents) in limited microbiological assays. The direct coupling of protected 4a to carbacephalosporins 16 and 17 and subsequent deprotection gave conjugates 20 and 21. The Lorabid conjugate 21 was especially active against E. coli X580 in preliminary biological tests, thus demonstrating the continued potential of siderophore-mediated drug delivery.

  DOI：

  10.1021/jo00084a018

文献信息

• Desketoneoenactin-Siderophore Conjugates for <i>Candida</i> : Evidence of Iron Transport-Dependent Species Selectivity
  作者：Geneviève Bernier、Vinay Girijavallabhan、Aaron Murray、Noormohamed Niyaz、Pingyu Ding、Marvin J. Miller、François Malouin

  DOI：10.1128/aac.49.1.241-248.2005

  日期：2005.1

  We investigated the inhibitory activity of synthetic isocyanurate-based as well as linear mono- and trihydroxamate siderophore-drug conjugates against Candida spp. The conjugated drug was 13C-desketoneoenactin (DE). The MICs of siderophore-drug conjugates were determined in the absence and presence of 2,2′-dipyridyl to restrict iron availability. The ability of various siderophore types to promote growth in an iron-restricted medium was also assayed. Addition of a siderophore portion to the drug strongly impaired the inhibitory activity of DE. However, the activity of the drug conjugates was increased by up to 16-fold in iron-depleted medium for species having their growth strongly promoted by most hydroxamate-type siderophores ( C. albicans , C. stellatoidea , and C. pseudotropicalis ). The uptake of ⁵⁵ Fe from ferrichrome and from two siderophore-drug conjugates was improved when C. albicans cells were grown in a low-iron medium. In the same assay, unlabeled ferrichrome was able to compete with the uptake of ⁵⁵ Fe from both conjugates, indicating a common mechanism of uptake. A C. albicans strain lacking the siderophore transporter CaSit1/CaArn1 was not able to use ferrichrome or the synthetic ornithine-based trihydroxamate siderophore for growth promotion and was much less susceptible to the siderophore-drug conjugates than its isogenic parent strain. In summary, the ability of some Candida spp. to use ferrichrome-like siderophores for growth promotion explains the selective activity of hydroxamate-drug conjugates, and this activity seems to be related to the presence, in C. albicans , of the siderophore transporter CaSit1/CaArn1. New conjugate designs are necessary to fully restore or improve the initial DE activity.

  摘要 我们研究了合成的异氰脲酸酯以及线性单羟基和三羟基氨基甲酸酯苷酸-药物共轭物对念珠菌的抑制活性。 念珠菌 13C-desketoneoenactin (DE)。在没有和有 2,2′-二吡啶限制铁的情况下，测定了嗜苷酸盐-药物共轭物的 MICs。此外，还测定了各种类型的嗜苷酸盐在铁限制培养基中促进生长的能力。在药物中加入嗜苷酸盐部分会大大削弱 DE 的抑制活性。然而，在缺铁培养基中，对于大多数羟酰胺类嗜苷酸盐能强烈促进生长的菌种（白念珠菌）来说，药物共轭物的活性最多可提高 16 倍。 白僵菌 , 白僵菌 和 C. pseudotropicalis ).吸收 55 铁铬和两种苷元-药物共轭物中铁的吸收率在 白僵菌 细胞在低铁培养基中生长时，其对 55 Fe 的吸收率有所提高。在同一试验中，未标记的亚铁铬能够与白僵菌细胞对 55 Fe 的吸收竞争。 55 铁的吸收，这表明两种共轭物具有共同的吸收机制。A 白僵菌 菌株不能利用亚铁铬或合成的基于鸟氨酸的三羟基氨基甲酸酯苷酸促进生长，而且对苷酸盐-药物共轭物的敏感性比其同源亲本菌株低得多。总之，一些 念珠菌 菌属能利用类似亚铁铬的嗜铁素促进生长，这解释了羟氨酸盐-药物共轭物的选择性活性。 白僵菌 中存在嗜苷酸盐转运体 CaSit1/CaArn1。有必要设计新的共轭物来完全恢复或提高最初的 DE 活性。
• Iron Transport-Mediated Drug Delivery: Synthesis and Biological Evaluation of Cyanuric Acid-Based Siderophore Analogs and .beta.-Lactam Conjugates
  作者：Manuka Ghosh、Marvin J. Miller

  DOI：10.1021/jo00084a018

  日期：1994.3

  Trihydroxamate-containing isocyanurates 4a-c were synthesized and determined to be capable of substituting for natural siderophores (microbial iron sequestering agents) in limited microbiological assays. The direct coupling of protected 4a to carbacephalosporins 16 and 17 and subsequent deprotection gave conjugates 20 and 21. The Lorabid conjugate 21 was especially active against E. coli X580 in preliminary biological tests, thus demonstrating the continued potential of siderophore-mediated drug delivery.