Development of M5 Selective Muscarinic Antagonists

We will first build and refine the 3D models of M1 to M5 mAChRs and examine their binding with the available antagonists. Then, we will examine how receptors interact with other ligands involved in this project and have a more extensive understanding of the SAR for available antagonists. By using the 3D models of M1 to M5 mAChRs, we will computationally evaluate the affinities of possible new compounds for their binding with M1 to M5 mAChRs in order to estimate both the potency and selectivity of the new compounds. The computationally determined most promising candidate compounds that have both the high binding affinity and selectivity for M5 mAChR will be recommended for practical synthesis.