A new pyridazine series of GABAA alpha5 ligands.
van Niel MB,
Wilson K,
Adkins CH,
Atack JR,
Castro JL,
Clarke DE,
Fletcher S,
Gerhard U,
Mackey MM,
Malpas S,
Maubach K,
Newman R,
O'Connor D,
Pillai GV,
Simpson PB,
Thomas SR,
MacLeod AM.
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM20 2QR, United Kingdom. monique_vanniel@merck.com
Screening of the Merck compound collection identified 6 as an unusually simple, low molecular weight hit with moderate affinity for GABAA receptors. The structural novelty of 6, compared to our advanced series of GABAA alpha5 inverse agonists, made it an attractive molecule for further exploration. This paper will describe the evolution of 6 into a new series of ligands with nanomolar affinity and functional selectivity for GABAA alpha5 receptor subtypes.
PMID: 16162003 [PubMed - indexed for MEDLINE]