凝血因子VIIa抑制剂：一种提高口服生物利用度的前药策略。
Factor VIIa inhibitors: a prodrug strategy to improve oral bioavailability.
作者信息
Riggs Jennifer R, Kolesnikov Aleksandr, Hendrix John, Young Wendy B, Shrader William D, Vijaykumar Dange, Stephens Robin, Liu Liang, Pan Lin, Mordenti Joyce, Green Michael J, Sukbuntherng Juthamas
机构信息
Celera Genomics, 180 Kimball Way, South San Francisco, CA 94080, USA.
出版信息
Bioorg Med Chem Lett. 2006 Apr 15;16(8):2224-8. doi: 10.1016/j.bmcl.2006.01.039. Epub 2006 Feb 3.
We have developed a series of potent and selective factor VIIa inhibitors based on the 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid scaffold. These amidine-containing compounds have low oral bioavailability. Herein, we describe our efforts to improve the oral bioavailability of the parent amidine via a prodrug strategy where the amidine basicity and polarity were reduced with either an alkoxy-amidine or a carbamate prodrug.
我们基于2-[5-(5-脒基-1H-苯并咪唑-2-基)-6-羟基-联苯-3-基]-琥珀酸支架开发了一系列强效且选择性的因子VIIa抑制剂。这些含脒的化合物口服生物利用度较低。在此，我们描述了通过前药策略提高母体脒口服生物利用度的努力，在前药策略中，通过烷氧基-脒或氨基甲酸酯前药降低了脒的碱性和极性。
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