Development of Synthetic Strategies for the Construction of Pyrido[4,3-d]pyrimidine Libraries - the Discovery of a New Class of PDE-4 Inhibitors

The synthesis of a pyrido[4,3‐d]pyrimidine library from 4,6‐diamino‐2‐bromonicotinamide and 4,6‐diaminonicotinamide is described. A systematic variation of the substituents at positions 2, 4, 5 and 7 of the pyrido[4,3‐d]pyrimidine scaffold was carried out, leading to a wide variety of structural analogues. This strategy led to the discovery of a new structural class of PDE‐4 inhibitors. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)