Basic Information
ID: ALA4610000
Journal: Bioorg Med Chem Lett
Title: Discovery of structurally distinct tricyclic M4 positive allosteric modulator (PAM) chemotypes.
Authors: Temple KJ, Long MF, Engers JL, Watson KJ, Chang S, Luscombe VB, Rodriguez AL, Niswender CM, Bridges TM, Conn PJ, Engers DW, Lindsley CW.
Abstract: This Letter details our efforts to develop new M4 PAM scaffolds with improved pharmacological properties. This endeavor involved replacing the 3,4-dimethylpyridazine core with two novel cores: a 2,3-dimethyl-2H-indazole-5-carboxamide core or a 1-methyl-1H-benzo[d][1,2,3]triazole-6-carboxamide core. Due to shallow SAR, these cores were further evolved into two unique tricyclic cores: an 8,9-dimethyl-8H-pyrazolo[3,4-h]quinazoline core and an 1-methyl-1H-[1,2,3]triazolo[4,5-h]quinazoline core. Both tricyclic cores displayed low nanomolar potency against both human and rat M4.
CiteXplore: 31787491
DOI: 10.1016/j.bmcl.2019.126811
Patent ID: ┄
Associated Items: Associated Bioactivities Associated Assays Associated Compounds Associated Targets