申请人:Merrell Pharmaceuticals, Inc.
公开号:US05728874A1
公开(公告)日:1998-03-17
The present invention relates to achiral polyurea oligomers, their uses and formulations as anti-HIV pharmaceuticals and to a process for the preparation of narrow mono- and polydispersed oligomers as an emodiment of the invention. The achiral oligomers are derived from repeating units of the monomer 4,4'-diamino-biphenyl-3,3'-disulfonic acid and are water soluble, have a rigid backbone, possess ordered anionic spacing and have a number average molecular weight of <20,000. The process relates to the synthesis of narrow poly- and mono-dipersed oligomers comprising the steps of: 1) restricting the crude olydispersed anionic oligomer mixture to a narrow polydispersed anionic oligomer mixture to a narrow polydispersed anionic oligomer mixture; and/or 2) isolating the monodispersed anionic oligomer; and 3) optionally converting the narrow poly- or mono-dispersed anionic oligomer salt from Step 1 or 2 to a desired pharmaceutically-acceptable salt, especially a solim or potassium salt. The process steps may be executed whereby step 1 or 2 is done alone, each in combination with Step 3, or all three steps are done.
本发明涉及无手性聚氨酯寡聚体,其用途和配方作为抗HIV药物,并涉及一种制备窄单分散和多分散寡聚体的过程,作为本发明的实施方式。无手性寡聚体由单体4,4'-二氨基联苯-3,3'-二磺酸重复单元衍生而来,水溶性,具有刚性骨架,有序阴离子间隔,具有小于20,000的数均分子量。该过程涉及到合成窄多分散和单分散寡聚体的步骤,包括:1)将原始多分散阴离子寡聚体混合物限制为窄多分散阴离子寡聚体混合物;和/或2)分离单分散阴离子寡聚体;以及3)可选地将步骤1或2中的窄多分散或单分散阴离子寡聚体盐转化为所需的药用可接受盐,特别是氯化锶或氯化钾盐。可以执行步骤1或2单独完成,每个步骤与步骤3相结合完成,或者完成所有三个步骤。