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A Agonists. -Among the new compounds, derivatives (IIIa) and (IIIe) are the most interesting ones having a good in vitro affinity for the α1 receptor and a potent in vivo induction of sedation. -(FALCO*, J. L.; PIQUE, M.; GONZALEZ, M.; BUIRA, I.; MENDEZ, E.; TERENCIO, J.; PEREZ, C.; PRINCEP, M.; PALOMER, A.; GUGLIETTA, A.; Eur. J. Med. Chem. 41 (2006) 8, 985-990; Dep. Med. Chem., R&D Cent., Ferrer Int. S.A.,

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Fused pyridine derivatives R 0450Design, Synthesis and Biological Activity of Acyl Substituted 3-Amino-5-methyl-1,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones as Potential Hypnotic Drugs.-A library of pyrazolopyridine derivatives [cf. (VI), (X), (XI)] is synthesized and evaluated for α1-GABA4 receptor affinity. None of these compounds show significant inhibitory activity. -(FALCO*, J. L.; LLOVERAS, M.; BUIRA, I.; TEIXIDO, J.; BORRELL, J. I.; MENDEZ, E.; TERENCIO, J.; PALOMER, A.; GUGLIETTA, A.; Eur.

An efficient solid-phase synthesis of 2-substituted 4-aminopyrido[2,3-d]pyrimidines 12 by cyclization-assisted cleavage from resin is reported. The procedure starts by solid supporting an alpha,beta-unsaturated acid 8 to the Wang resin 13 by using DCC and 4-DMAP in THF. The resulting alpha,beta-unsaturated ester 14 is converted to the Michael adduct by treatment with malononitrile in NaOMe/THF. Such Michael addition constitutes the first example of a Michael reaction with malononitrile in solid-phase. Finally, the Michael adducts 15 are treated with an amidine system in MeOH to yield the corresponding pyridopyrimidines 12. Compounds 12 present three diversity centers R1, R2 and G. Having validated the chemistry on solid support, a 40-membered combinatorial library was obtained using this protocol.