title: Benzamide bioisosteres incorporating dihydroheteroazole substructures: EPC synthesis and SAR leading to a selective dopamine D4 receptor partial agonist (FAUC 179).
abstract: Conformationally restricted benzamide bioisosteres were investigated when the chiral phenyldihydroimidazole derivative 4e (FAUC 179) showed strong and highly selective dopamine D4 receptor binding (K(i)high=0.95nM). Mitogenesis experiments indicated partial agonist properties (42%). EPC syntheses of the target compounds of type 4 were performed starting from alpha-amino acids.
authors.affiliation: Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052, Erlangen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Einsiedel
authors.forename: H
authors.initials: H
authors.lastname: Hübner
authors.forename: P
authors.initials: P
authors.lastname: Gmeiner
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D016466:CHO Cells; D002417:Cattle; D003024:Clozapine / Q000494:pharmacology; D006224:Cricetinae; D003545:Cysteine / Q000737:chemistry; D018492:Dopamine Antagonists / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050638:Receptors, Dopamine D4; D012694:Serine / Q000737:chemistry; D013134:Spiperone / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013912:Threonine / Q000737:chemistry
chemical_list: C493599:DRD4 protein, human; D018492:Dopamine Antagonists; C448503:FAUC 179; D007211:Indoles; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D019257:Quinpirole; D013912:Threonine; D012694:Serine; D013134:Spiperone; D003024:Clozapine; D003545:Cysteine