title: Synthesis andin vitropharmacological evaluation of indolyl carboxylic amide analogues as D3dopamine receptor selective ligands.
abstract: A series of substituted 1H-indolyl carboxylic acid amides that contain aN-(2-methoxyphenyl)piperazine orN-(2-fluoroethoxy)piperazine group were synthesized and their affinities for human dopamine D2, D3, and D4receptors were determined. Two of these compounds,14aand14b, displayed high binding affinity at D3(Ki= 0.18 and 0.4 nM, respectively), and selectivity for D3vs.D2receptors (87-fold and 60-fold, respectively). These two compounds had low binding affinity at D4receptors and σ receptor sites. The intrinsic activity of these compounds at D2and D3receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay; both14aand14bwere found to be partial agonists. Furthermore, for compound14a, the logDvalue of 2.85 suggested it has suitable lipophilicity for crossing the blood-brain-barrier.
authors.affiliation: Washington University School of Medicine, St. Louis, MO, 63110, USA., ; Tel: +1-314-362-8538.
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.forename: Aixiao
authors.initials: A
authors.lastname: Li
authors.forename: Michelle
authors.initials: M
authors.lastname: Taylor
authors.forename: David
authors.initials: D
authors.lastname: Ho
authors.forename: Maninder
authors.initials: M
authors.lastname: Malik
authors.forename: Robert R
authors.initials: RR
authors.lastname: Luedtke
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach