SQ109的氨基甲酸酯前药作为抗结核药物的合成与评价
Synthesis and evaluation of carbamate prodrugs of SQ109 as antituberculosis agents.
作者信息
Meng Qingyi, Luo Huibing, Liu Yibin, Li Wei, Zhang Wen, Yao Qizheng
机构信息
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
出版信息
Bioorg Med Chem Lett. 2009 May 15;19(10):2808-10. doi: 10.1016/j.bmcl.2009.03.091. Epub 2009 Mar 26.
The low bioavailability of SQ109 in rats, resulting from first-pass effect in the liver, may be remedied by prodrug strategy. Based on esterase-sensitive carbamate prodrug strategy, a novel series of prodrugs of SQ109 has been reported. Bioavailability of SQ109 after administration of prodrug 7a was 91.4% compared with 21.4% after oral administration of SQ109. After oral administration of compound 7a, the parent drug SQ109 exhibited preferential tissue distribution into lung and spleen, the target organs of tubercular infection and replication.
SQ109在大鼠体内生物利用度较低，这是由肝脏首过效应导致的，可通过前药策略加以改善。基于酯酶敏感的氨基甲酸酯前药策略，已报道了一系列新型的SQ109前药。前药7a给药后，SQ109的生物利用度为91.4%，而口服SQ109后的生物利用度为21.4%。口服化合物7a后，母体药物SQ109在肺和脾中呈现出优先的组织分布，肺和脾是结核感染和复制的靶器官。
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