Design, 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.

Abstract Among the known non-benzodiazepinic hypnotic drugs acting on the α1 subunit of the GABA-A receptor, Zolpidem ( 2a ), Zaleplon ( 1b ) and Indiplon ( 1a ) have showed high affinity and selectivity. Following a design methodology including pharmacophoric requirements and ADME-predicted properties, we have synthesized a library of 3-amino-4,5-dihydro-1 H -pyrazolo[3,4- b ]pyridin-6(7 H )-ones ( 3 ) and their N1-alkyl derivatives ( 4) as new scaffolds for designing non-benzodiazepine BZ receptor ligands.