Synthesis of piperazinones and their application in constrained mimetics of the growth hormone secretagogue NN703

The focus of this paper is the chemistry of 2-piperazinones and the use of this building block to restrict the conformational freedom of the growth ho rmone secretagogue NN703 (currently in clinical development). We exploit cl assical methods for 2-piperazinone synthesis as well as some novel approach es such as a Boronic Mannich reaction. Finally. we report on the ability of the constrained target compounds to release growth hormone in vitro. (C) 1 999 Elsevier Science Ltd. All rights reserved.