申请人:Isis Pharmaceuticals, Inc.
公开号:US06107482A1
公开(公告)日:2000-08-22
Novel macrocyclic compounds are constructed to include large cyclic structures that are interrupted by at least one ring system. Each interrupting ring system includes two bridgehead atoms. Bridgehead atoms are bonded to one or more bridges that interconnect one or more ring systems thereby forming a large cyclic structure. Located in each bridge are two or more nitrogenous moieties that are derivatized with chemical functional groups. The ring systems can include further nitrogenous moieties, either as ring atoms or on pendant groups attached to the ring. These can also be derivatized with chemical functional groups. The totality of the chemical functional groups imparts certain conformational and other properties to the macrocyclic compounds. In accordance with certain embodiments of the invention, libraries of such macrocyclic compounds are prepared utilizing permutations and combinations of the chemical functional groups and the nitrogenous moieties to build complexity into the library.
新型大环化合物被构建成包含至少一个环系统打断的大环结构。每个打断的环系统包括两个桥头原子。桥头原子与一个或多个桥连接,连接一个或多个环系统,从而形成一个大环结构。每个桥中都含有两个或更多的氮基团,这些氮基团经过化学官能团衍生。环系统可以包括进一步的氮基团,可以是环原子,也可以是连接到环上的侧链基团。这些也可以经过化学官能团衍生。化学官能团的总体赋予大环化合物特定的构象和其他性质。根据发明的某些实施例,利用化学官能团和氮基团的排列组合制备这种大环化合物的文库,以在文库中构建复杂性。