C32-O-imidazol-2-yl-methyl ether derivatives of the immunosuppressant ascomycin with improved therapeutic potential

Article abstract of DOI:10.1016/S0960-894X(98)00397-7

A series of C32-O-aralkyl ether derivatives of the FK-506 related macrolide ascomycin have been prepared based on an earlier reported C32-O- cinnamyl ether design. In the present study, the nature of the aryl tethering group was varied in an attempt to improve oral activity. An imidazol-2-yl- methyl tether was found to be superior among those investigated and has resulted in an ascomycin analog, L-733,725, with in vivo immunosuppressive activity comparable to FK-506 but with an improved therapeutic index.