Oral Delivery of Propofol with Methoxymethylphosphonic Acid as the Delivery Vehicle
| Autor: | Liao Pengfei, Lu Yonghua, Luo Xinfeng, Linlin Qin, Wei Yonggang, Gao Qiu, Huang Qingping, Ni Jia, Qiu Guanpeng, Yan Pangke, Qian Guofei, Pan Li, Zhu Guozhi, Xia Huang, Chu Hongzhu, Tang Pingming, Yi Zhou, Aisheng Gong, Zheng Suxin, Jianyu Liu, Xiaowei Zhang, Lei Bailin, Li Yao, Yu Yan, Chen Zhang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Spectrometry Mass Electrospray Ionization Magnetic Resonance Spectroscopy Organophosphonates Administration Oral Pharmacology 01 natural sciences Mice 03 medical and health sciences Dogs 0302 clinical medicine Drug Discovery medicine Animals Hypnotics and Sedatives Propofol Drug Carriers Mice Inbred ICR 010405 organic chemistry Chemistry Delivery vehicle Ethyl ester 0104 chemical sciences Bioavailability Plasma concentration Molecular Medicine Female Drug carrier 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 60:8580-8590 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.7b01133 |
| Popis: | Phosphonamidate 3a of methoxymethylphosphonic acid (MMPA) with propofol (1) and l-alanine ethyl ester was found to be an efficient scaffold for the oral delivery of compound 1. The synthesis and evaluation of MMPA based phosphonamidates of compound 1, HSK3486 (2), and other phenolic drugs revealed the general application of MMPA as the effective delivery vehicle for phenolic drugs. On the basis of plasma concentrations of compound 1 and SN38 (14), the oral bioavailability of compound 3a and 15 in beagle dogs was found to be 97.6% and 34.1%, respectively. |
| Databáze: | OpenAIRE |
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