Carolina Martinez-Lamenca

TL;DR: Lead optimization focused on reducing the amidine pKa while optimizing interactions in the BACE1 active site led to compounds which were orally bioavailable, centrally active, and which demonstrated robust lowering of brain and CSF Aβ levels, respectively, in mouse and dog models.

TL;DR: A general synthesis of CF3-sulfonimidamides from sulfinamides under both batch and continuous flow conditions is described.

TL;DR: The general synthesis of CF3-sulfonimidamides from an activated bench-stable transfer reagent is described, and a diverse reaction scope is demonstrated, with a wide range of nucleophilic amines being tolerated in this transformation.

TL;DR: Optimization resulted in the replacement of the 2-fluoro substituent by a CF3-group, which reduced hERG inhibition and led to compound 3, with an improved cardiovascular safety margin and sufficiently safe in GLP toxicity studies to progress into clinical trials.

TL;DR: In this paper, a simple and scalable procedure to introduce alcohols selectively at the 3position of 3,4,5-trifluoroaniline is described, using powdered NaOH as base and catalytic 15-crown-5 in refluxing toluene with a Dean-Stark trap.