title: New substituted 1-(2,3-dihydrobenzo[1, 4]dioxin-2-ylmethyl)piperidin-4-yl derivatives with alpha(2)-adrenoceptor antagonist activity.
abstract: The emergence of a novel theory concerning the role of noradrenaline in the progression and the treatment of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases has provided a new impetus toward the discovery of novel compounds acting at alpha(2)-adrenoceptors. A series of substituted 1-(2, 3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-yl derivatives bearing an amide, urea, or imidazolidinone moiety was studied. Some members of this series of compounds proved to be potent alpha(2)-adrenoceptor antagonists with good selectivity versus alpha(1)-adrenergic and D(2)-dopamine receptors. Particular emphasis is given to compound 33g which displays potent alpha(2)-adrenoceptor binding affinity in vitro and central effects in vivo following oral administration.
authors.affiliation: Division of Medicinal Chemistry, Department of Analytical Chemistry, Centre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, 81100 Castres, France.
authors.forename: P
authors.initials: P
authors.lastname: Mayer
authors.forename: P
authors.initials: P
authors.lastname: Brunel
authors.forename: C
authors.initials: C
authors.lastname: Chaplain
authors.forename: C
authors.initials: C
authors.lastname: Piedecoq
authors.forename: F
authors.initials: F
authors.lastname: Calmel
authors.forename: P
authors.initials: P
authors.lastname: Schambel
authors.forename: P
authors.initials: P
authors.lastname: Chopin
authors.forename: T
authors.initials: T
authors.lastname: Wurch
authors.forename: P J
authors.initials: PJ
authors.lastname: Pauwels
authors.forename: M
authors.initials: M
authors.lastname: Marien
authors.forename: J L
authors.initials: JL
authors.lastname: Vidaluc
authors.forename: T
authors.initials: T
authors.lastname: Imbert
mesh_terms: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006143:Guanabenz; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes; D051379:Mice; D009457:Neuroglia / Q000378:metabolism; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C415156:1-(2-(1-(2,3-dihydrobenzo(1,4)dioxin-2-ylmethyl)piperidin-4-yl)ethyl)-3-(2,4,6-trimethoxyphenyl)imidazolidin-2-one; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D017448:Receptors, Dopamine D2; D006143:Guanabenz