6533b828fe1ef96bd128785a
RESEARCH PRODUCT
ChemInform Abstract: A Versatile Approach to CF3-Containing 2-Pyrrolidones by Tandem Michael Addition-Cyclization: Exemplification in the Synthesis of Amidine Class BACE1 Inhibitors.
Andrés A. TrabancoNatalia MateuLaura Pérez-benitoOscar DelgadoMaría Sánchez-rosellóGary TresadernSantos FusteroMichiel Van GoolMyriam CiordiaMyriam Ciordiasubject
Amidinechemistry.chemical_compoundTandemchemistryAmino estersDrug discoveryBiological propertyMichael reactionSequence (biology)General MedicineCombinatorial chemistryStereocenterdescription
The synthesis of new fluorinated pyrrolidones starting from unprotected amino esters and amino nitriles through a Michael addition-lactamization sequence is described. The resulting CF3 -containing building blocks, bearing a quaternary stereogenic center adjacent to the fluorinated group, have been converted into amino pyrrolidines that display potent β-secretase 1 (BACE1) inhibitory activity. This work constitutes an example of selective fluorination as a valid strategy for the modulation of physicochemical and biological properties of lead compounds in drug discovery.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-01 | ChemInform |