Roberto Profeta

Discovery of N-[(2S)-5-(6-Fluoro-3-Pyridinyl)-2,3-Dihydro-1H-Inden-2-Yl]-2-Propanesulfonamide, a Novel Clinical Ampa Receptor Positive Modulator.

A series of AMPA receptor positive allosteric modulators has been optimized from poorly penetrant leads to identify molecules with excellent preclinical pharmacokinetics and CNS penetration. These discoveries led to 17i, a potent, efficacious CNS penetrant molecule with an excellent pharmacokinetic profile across preclinical species, which is well tolerated and is also orally bioavailable in humans.

Highly diastereoselective addition of nitromethane anion to chiral ?-amidoalkylphenyl sulfones. Synthesis of optically active ?-amino acid derivativesElectronic supplementary information (ESI) available: Computational results output for the calculated structures. Transition state models leading to compounds 21 and 22. See http://www.rsc.org/suppdata/ob/b3/b309211a/

Optically active syn-α-amidoalkylphenyl sulfones can be prepared from chiral aldehydes in anhydrous conditions using benzenesulfinic acid. These sulfones in basic conditions give N-acylimines that react with sodium methanenitronate to afford the corresponding nitro adducts with high anti diastereoselectivity. PM3 semiempirical calculations provide a rationale for the observed opposite stereoselectivity. The obtained nitro derivatives undergo a Nef reaction followed by a methylation giving optically active β-hydroxy-α-amino acid and α,β-diamino acid esters in good yield. These amino acid derivatives are important building blocks for the preparation of biologically active compounds.

Regioselective Preparationof N-Methylpyrazole Derivative

A novel high-yielding and regioselective method to prepare N-methylpyrazole derivative is reported, by reaction of an N-Boc- and N-Me-substituted hydrazone with an aromatic alkyl ester.