title: New generation dopaminergic agents. 5. Heterocyclic bioisosteres that exploit the 3-OH-N1-phenylpiperazine dopaminergic template.
abstract: The synthesis of several bioisosteric analogs based on the 3-OH-N1-phenylpiperazine dopamine D2 agonist template (i.e., 4) is described. The indolone (5) and 2-CF3-benzimidazole (13) were observed to have excellent affinity for the D2 receptor. Several D4 selective compounds were also identified. Molecular modeling studies and a putative bioactive conformation are discussed.
authors.affiliation: Global Chemical Sciences, Wyeth-Ayerst Research Laboratory, Princeton, NJ 08543-8000, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Mewshaw
authors.forename: A
authors.initials: A
authors.lastname: Verwijs
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: G B
authors.initials: GB
authors.lastname: McGaughey
authors.forename: J A
authors.initials: JA
authors.lastname: Nelson
authors.forename: H
authors.initials: H
authors.lastname: Mazandarani
authors.forename: J A
authors.initials: JA
authors.lastname: Brennan
authors.forename: K L
authors.initials: KL
authors.lastname: Marquis
authors.forename: J
authors.initials: J
authors.lastname: Coupet
authors.forename: T H
authors.initials: TH
authors.lastname: Andree
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000138:chemical synthesis / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3; D013329:Structure-Activity Relationship; D013698:Templates, Genetic
chemical_list: D001562:Benzimidazoles; D015259:Dopamine Agents; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D007211:Indoles; D010879:Piperazines; D011619:Psychotropic Drugs; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C031503:phenylpiperazine