title: Novel azulene derivatives for the treatment of erectile dysfunction.
abstract: Based on the dopamine D(4) receptor partial agonist FAUC 3019, a series of azulenylmethylpiperazines was synthesized and affinities for the monoaminergic GPCRs including dopamine, serotonin, histamine and α-adrenergic receptor subtypes were determined. Ligand efficacies of the most promising test compounds revealed the N,N-dimethylaminomethyl substituted azulene 11 to be the most potent D(4) partial agonist (EC(50)=0.41 nM). This candidate was investigated for its ability to promote penile erection. Applying an in vivo animal model, test compound 11 turned out to stimulate penile erection in male rats with superior potency in low concentrations when compared to apomorphine.
authors.affiliation: Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Löber
authors.forename: Harald
authors.initials: H
authors.lastname: Hübner
authors.forename: Armin
authors.initials: A
authors.lastname: Buschauer
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Sanna
authors.forename: Antonio
authors.initials: A
authors.lastname: Argiolas
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Melis
authors.forename: Peter
authors.initials: P
authors.lastname: Gmeiner
mesh_terms: D000818:Animals; D052176:Azulenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D007700:Kinetics; D008297:Male; D008744:Methylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000819:agonists / Q000378:metabolism; D011968:Receptors, Histamine / Q000737:chemistry / Q000378:metabolism; D013552:Swine
chemical_list: D052176:Azulenes; C579673:FAUC 3019; D008744:Methylamines; D011954:Receptors, Dopamine; D011968:Receptors, Histamine; D050638:Receptors, Dopamine D4; C005525:azulene