Design and identification of a novel, functionally subtype selective GABA positive allosteric modulator (PF-06372865).

08:00 EDT 9th April 2019 | BioPortfolio

Summary of "Design and identification of a novel, functionally subtype selective GABA positive allosteric modulator (PF-06372865)."

The design, optimization and evaluation of a series of novel imidazopyridazine-based subtype-selective positive allosteric modulators (PAMs) for the GABA ligand-gated ion channel are described. From a set of initial hits multiple subseries were designed and evaluated based on binding affinity and functional activity. As designing in the desired level of functional selectivity proved difficult, a probability-based assessment was performed to focus the project's efforts on a single subseries which had the greatest odds of delivering the target profile. These efforts ultimately led to the identification of two pre-candidates from this subseries, which were advanced to pre-clinical safety studies and subsequently to the identification of the clinical candidate PF-06372865.


Journal Details

This article was published in the following journal.

Name: Journal of medicinal chemistry
ISSN: 1520-4804


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