The first solid-phase synthesis of zatebradine 1 and its analogues is reported. This has resulted in the preparation of compounds with increased ability to reduce the spontaneous beating of isolated guinea-pig atria in a concentration-dependent manner. One example, 8g, showed a maximum reduction of beating of 80% at 3 microM compared to a reduction of 40% at 3 microM with zatebradine 1.

This Report reviews literature published Nov 1996-Dec 97; it is the third in a series that summarises organic reactions performed on solid supports and is designed as an update to Tetrahedron Reports no. 394 and 418. The reactions are presented in a graphical abstract format and examples are given of the following reactions: amide formation, aromatic substitution (nucleophilic/electrophilic), cleavage, condensation, cycloaddition, deprotection/protection, Grignard and related reactions, heterocycle formation, immobilisation onto resin, Michael addition, miscellaneous, multiple component condensation, olefin formation, oxidation, reduction and substitution (nucleophilic/electrophilic). Solid-phase peptide or other oligomer synthesis and reactions using soluble polymeric supports are not included. This report ends with the discussion of some trends in the domain under consideration. (C) 1998 Elsevier Science Ltd. All rights reserved.