title: 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 alpha1 subunit of the GABA-A receptor, Zolpidem, Zaleplon and Indiplon 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-1H-pyrazolo[3,4-b]pyridin-6(7H)-ones and their N1-alkyl derivatives as new scaffolds for designing non-benzodiazepine BZ receptor ligands.
authors.affiliation: Medicinal Chemistry Department, R and D Center, Ferrer Internacional S.A., Juan de Sada 32, E-08028 Barcelona, Spain. jlfalco-research@ferrergrupo.com
authors.forename: José L
authors.initials: JL
authors.lastname: Falcó
authors.forename: Maia
authors.initials: M
authors.lastname: Lloveras
authors.forename: Irma
authors.initials: I
authors.lastname: Buira
authors.forename: Jordi
authors.initials: J
authors.lastname: Teixidó
authors.forename: José I
authors.initials: JI
authors.lastname: Borrell
authors.forename: Eva
authors.initials: E
authors.lastname: Méndez
authors.forename: José
authors.initials: J
authors.lastname: Terencio
authors.forename: Albert
authors.initials: A
authors.lastname: Palomer
authors.forename: Antonio
authors.initials: A
authors.lastname: Guglietta
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology; D000077334:Zolpidem
chemical_list: D006993:Hypnotics and Sedatives; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D011963:Receptors, GABA-A; D013876:Thiophenes; D001569:Benzodiazepines; D000077334:Zolpidem; C469870:indiplon