This invention is directed to novel crystalline solvates of the (S)-P diastereomer of the anti- HCV nucleoside phosphoroamidate, (2S)-neopentyl 2-((((2R,3R,4R,5R)-5-(2-amino-6- methoxy-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(naphthalen- l-yloxy)phosphorylamino)propanoate (also referred to as INX-08189 or IΝΧ-189), and to a recrystallization method for separating the two diastereomers of INX-08189. In addition, this application relates to a novel stereoselective method for the preparation of either of the two diastereomers, and to the novel synthetic intermediates used in this stereoselective synthesis. The invention also relates to the use of the crystalline solvates to increase the liver exposure of 2'-C-methyl guanosine triphosphate from an oral dose.
该发明涉及抗HCV核苷
磷酸酰胺的(S)-P对映体的新型晶体溶剂化合物,(2S)-新戊基2-((((2R,3R,4R,5R)-5-(2-
氨基-6-甲氧基-9H-
嘌呤-9-基)-3,4-二羟基-4-甲基
四氢呋喃-2-基)甲氧基)(
萘基氧基)
磷酰胺)
丙酸酯(也称为INX-08189或INX-189),以及用于分离INX-08189两个对映体的重结晶方法。此外,该申请涉及一种新颖的立体选择性制备两个对映体的方法,以及用于这种立体选择性合成的新型合成中间体。该发明还涉及利用晶体溶剂化合物提高2'-C-甲基
鸟苷三磷酸酯从口服剂量中的肝脏暴露。