Wei Yonggang, Qiu Guanpeng, Lei Bailin, Qin Linlin, Chu Hongzhu, Lu Yonghua, Zhu Guozhi, Gao Qiu, Huang Qingping, Qian Guofei, Liao Pengfei, Luo Xinfeng, Zhang Xiaowei, Zhang Chen, Li Yao, Zheng Suxin, Yu Yan, Tang Pingming, Ni Jia, Yan Pangke, Zhou Yi, Li Pan, Huang Xia, Gong Aisheng, Liu Jianyu
Haisco Pharmaceuticals Group Co. Ltd. , 136 Baili Road, Wenjiang District, Chengdu, 611130, China.
J Med Chem. 2017 Oct 26;60(20):8580-8590. doi: 10.1021/acs.jmedchem.7b01133. Epub 2017 Oct 12.
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.
发现甲氧基甲基膦酸（MMPA）与丙泊酚（1）和L-丙氨酸乙酯形成的磷酰胺酯3a是用于化合物1口服给药的有效骨架。对基于MMPA的化合物1、HSK3486（2）及其他酚类药物的磷酰胺酯进行合成和评估后，发现MMPA可作为酚类药物的有效递送载体广泛应用。根据化合物1和SN38（14）的血浆浓度，发现比格犬中化合物3a和15的口服生物利用度分别为97.6%和34.1%。
