1 Department of Organic Chemistry, Technical University of Denmark2 Department of Chemistry, Technical University of Denmark
The present invention relates to a solid phase methodology for the preparation of a combinatorial library of structural analogues of the natural product balanol (ophiocordin, azepinostatin), which is a protein kinase C (PKC) and protein kinase A (PKA) inhibitor. The method comprises solid-phase synthesis of the analog variants of balanol whereby a high molecular diversity is introduced. The synthetic scheme is based on a retrosynthetic analysis of the native structure which revealed three main building blocks suitable as templates for modification. The dicarboxy-functional moiety can be immobilised to the polymer support either as the monoallyl ester or as the internal anhydride. The libraries produced by the method are especially suited for high throughput screening of potential drug candidates for the treatment of mammals, especially humans.