Department of Medicinal Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
J Med Chem. 2013 Feb 28;56(4):1670-6. doi: 10.1021/jm301638a. Epub 2013 Feb 12.
In vitro studies suggested that the ammonium salt 2 could be a viable prodrug of the HIV-1 attachment inhibitor 1. Increased systemic exposure of the parent drug 1 following oral administration of the amminium salt 2 when compared to similar studies using solution dosing of the parent compound was observed in the in vivo studies in both rats and dogs. At high doses, the improvement in oral exposure of the parent drug was even more evident, indicating that the increased solubility of the amminium salt 2 can overcome dissolution-limited absorption and demonstrating the potential utility of this compound as a prodrug of 1.
体外研究表明，铵盐 2 可能是 HIV-1 附着抑制剂 1 的一种有前途的前药。在大鼠和狗的体内研究中，与使用母体化合物溶液给药的类似研究相比，口服铵盐 2 后母体药物 1 的全身暴露增加。在高剂量下，母体药物口服暴露的改善更为明显，表明铵盐 2 的溶解度增加可以克服溶解限制吸收，并表明该化合物作为 1 的前药具有潜在的应用价值。
