Parallel solid-phase synthesis and characterization of new sulfonamide and carboxamide proline derivatives as potential CNS agents

A solid-phase synthesis of the 64-member library of novel sulfonamide and carboxamide proline derivatives, focused on the 5-HT7 receptor antagonist SB-258741, was described. The final compounds were obtained in good yields and high purity upon cleavage from SynPhase Lanterns, functionalized by a BAL linker. The library representatives were screened for 5-HT7, 5-HT1A and D2 receptors to explore the impact of a tertiary amine moiety, the length of an alkylene spacer and the aryl fragment on the receptor affinity. The preliminary biological results provided data for further investigation aimed at a search for 5-HT7 receptor agents, and permitted the identification of several compounds with significant 5-HT1A receptor affinity.

The parallel solid-phase synthesis of a series of sulfonamide and carboxamide proline derivatives and their in vitro binding affinities for serotonin 5-HT7, 5-HT1A and dopamine D2 receptors are presented.Figure optionsDownload as PowerPoint slide