Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment 13. Synthesis and Profiling of a Novel Amminium Prodrug of the HIV-1 Attachment Inhibitor BMS-585248

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• 作者：Alicia Regueiro-Ren ; Jean Simmermacher-Mayer ; Michael Sinz ; Kim A. Johnson ; Xiaohua Stella Huang ; Susan Jenkins ; Dawn Parker ; Sandhya Rahematpura ; Ming Zheng ; Nicholas A. Meanwell ; John F. Kadow
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：February 28, 2013
• 年：2013
• 卷：56
• 期：4
• 页码：1670-1676
• 全文大小：312K
• 年卷期：v.56,no.4(February 28, 2013)
• ISSN：1520-4804

文摘

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.