tert-butyl 3-((1,3-dihydroxypropan-2-yl)amino)propanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 3-((1,3-dihydroxypropan-2-yl)amino)propanoate
• 英文别名: Tert-butyl 3-(1,3-dihydroxypropan-2-ylamino)propanoate；tert-butyl 3-(1,3-dihydroxypropan-2-ylamino)propanoate
• 化学式: C₁₀H₂₁NO₄
• 分子量: 219.281
• InChiKey: TYBINILEBXZFTN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  78.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-((1,3-dihydroxypropan-2-yl)amino)propanoate 在 4-二甲氨基吡啶 、 三异丙基硅烷 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 30.0h， 生成 di-stearoylaminopropionic acid
  参考文献：
  名称：

  Novel two-chain fatty acid-based lipids for development of vancomycin pH-responsive liposomes against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA)

  摘要：

  The development of bacterial resistance against antibiotics is attributed to poor localisation of lethal antibiotic dose at the infection site. This study reports on the synthesis and use of novel two-chain fatty acid-based lipids (FAL) containing amino acid head groups in the formulation of pH-responsive liposomes for the targeted delivery of vancomycin (VAN). The formulated liposomes were characterised for their size, polydispersity index (PDI), surface charge and morphology. The drug-loading capacity, drug release, cell viability, and in vitro and in vivo efficacy of the formulations were investigated. A sustained VAN release profile was observed and in vitro antibacterial studies against S. aureus and MRSA showed superior and prolonged activity over 72 h at both pH 7.4 and 6.0. Enhanced antibacterial activity at pH 6.0 was observed for the DOAPA-VAN-Lipo and DLAPA-VAN-Lipo formulations. Flow cytometry studies indicated a high killing rate of MRSA cells using DOAPA-VN-Lipo (71.98%) and DLAPA-VN-Lipo (73.32%). In vivo studies showed reduced MRSA recovered from mice treated with formulations by four- and two-folds lower than bare VN treated mice, respectively. The targeted delivery of VAN can be improved by novel pH-responsive liposomes from the two-chain (FAL) designed in this study.

  DOI：

  10.1080/1061186x.2019.1599380
• 作为产物：
  描述：

  丙烯酸叔丁酯 、 丝氨醇 以 乙醇 为溶剂， 反应 4.0h， 以92%的产率得到tert-butyl 3-((1,3-dihydroxypropan-2-yl)amino)propanoate
  参考文献：
  名称：

  带有仲氨基酸酯头基的新型单，二和三脂肪酸酯，可作为透皮渗透增强剂†

  摘要：

  化学渗透促进剂（CPE）的使用拓宽了可通过透皮途径传递的药物库。本研究使用替诺福韦（TNF）作为模型药物，探索了具有β-丙氨酸叔丁酯头基的新型单，二和三脂肪酸（FA）酯的合成和表征，这些酯是经皮渗透促进剂。合成的化合物对哺乳动物细胞无毒，证实了其在药物应用中的安全性。与它们各自的单独的FA相比，所有合成的衍生物都表现出更好的透皮渗透增强能力。结果表明，脂肪族碳链数与增强比（ER）之间没有相关性。单油酸酯衍生物（MOAPE（4II））在1％w / w下显示出最大的TNF的ER（5.87）。与MOAPE（治疗大鼠皮肤组织调查4II）透露角质层的流化。组织学和用的调查结果证实了上皮电阻（TEER）研究体外渗透实验，并透露，有在1％MOAPE（皮肤的活力的表皮没有显著变化4II）曝光。该TEER调查结果还表明，MOAPE（渗透增强效果4II）不是永久性的，结果表明去除增强配方后对原皮的完整性回报。

  DOI：

  10.1039/c7nj04025c

文献信息

• Novel mono, di and tri-fatty acid esters bearing secondary amino acid ester head groups as transdermal permeation enhancers
  作者：S. Rambharose、R. S. Kalhapure、M. Jadhav、T. Govender

  DOI：10.1039/c7nj04025c

  日期：——

  transdermal route. This study explored the synthesis and characterization of novel mono, di and tri-fatty acid (FA) esters bearing β-alanine t-butyl ester head groups as transdermal permeation enhancers using tenofovir (TNF) as a model drug. The synthesized compounds were non-toxic to mammalian cells confirming their safety for pharmaceutical applications. All the synthesized derivatives displayed better

  化学渗透促进剂（CPE）的使用拓宽了可通过透皮途径传递的药物库。本研究使用替诺福韦（TNF）作为模型药物，探索了具有β-丙氨酸叔丁酯头基的新型单，二和三脂肪酸（FA）酯的合成和表征，这些酯是经皮渗透促进剂。合成的化合物对哺乳动物细胞无毒，证实了其在药物应用中的安全性。与它们各自的单独的FA相比，所有合成的衍生物都表现出更好的透皮渗透增强能力。结果表明，脂肪族碳链数与增强比（ER）之间没有相关性。单油酸酯衍生物（MOAPE（4II））在1％w / w下显示出最大的TNF的ER（5.87）。与MOAPE（治疗大鼠皮肤组织调查4II）透露角质层的流化。组织学和用的调查结果证实了上皮电阻（TEER）研究体外渗透实验，并透露，有在1％MOAPE（皮肤的活力的表皮没有显著变化4II）曝光。该TEER调查结果还表明，MOAPE（渗透增强效果4II）不是永久性的，结果表明去除增强配方后对原皮的完整性回报。
• [EN] PH-RESPONSIVE LIPIDS<br/>[FR] LIPIDES SENSIBLES AU PH
  申请人：UNIV OF KWAZULU NATAL

  公开号：WO2018033883A3

  公开（公告）日：2019-01-31
• PH-RESPONSIVE LIPIDS
  申请人：University of KwaZulu-Natal

  公开号：US20210317071A1

  公开（公告）日：2021-10-14

  The invention provides for a synthesised ester intermediate of formula 1. Formula 1 Wherein and wherein R may be a saturated or unsaturated fatty acid (C12-C20).
• Novel two-chain fatty acid-based lipids for development of vancomycin pH-responsive liposomes against <i>Staphylococcus aureus</i> and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)
  作者：Sifiso S. Makhathini、Rahul S. Kalhapure、Mahantesh Jadhav、Ayman Y. Waddad、Ramesh Gannimani、Calvin A. Omolo、Sanjeev Rambharose、Chunderika Mocktar、Thirumala Govender

  DOI：10.1080/1061186x.2019.1599380

  日期：2019.11.26

  The development of bacterial resistance against antibiotics is attributed to poor localisation of lethal antibiotic dose at the infection site. This study reports on the synthesis and use of novel two-chain fatty acid-based lipids (FAL) containing amino acid head groups in the formulation of pH-responsive liposomes for the targeted delivery of vancomycin (VAN). The formulated liposomes were characterised for their size, polydispersity index (PDI), surface charge and morphology. The drug-loading capacity, drug release, cell viability, and in vitro and in vivo efficacy of the formulations were investigated. A sustained VAN release profile was observed and in vitro antibacterial studies against S. aureus and MRSA showed superior and prolonged activity over 72 h at both pH 7.4 and 6.0. Enhanced antibacterial activity at pH 6.0 was observed for the DOAPA-VAN-Lipo and DLAPA-VAN-Lipo formulations. Flow cytometry studies indicated a high killing rate of MRSA cells using DOAPA-VN-Lipo (71.98%) and DLAPA-VN-Lipo (73.32%). In vivo studies showed reduced MRSA recovered from mice treated with formulations by four- and two-folds lower than bare VN treated mice, respectively. The targeted delivery of VAN can be improved by novel pH-responsive liposomes from the two-chain (FAL) designed in this study.