The azulene framework as a novel arene bioisostere: design of potent dopamine D4 receptor ligands inducing penile erection.
Blue makes it happen: The non-uniform charge distribution of the blue colored azulene framework is highly suitable for the bioisosteric replacement of bicyclic heteroarene moieties. Showing an analogous binding mode as heterocyclic dopamine D4 receptor-selective lead compounds, the induction of penile erection in rats over a greater range of doses indicates a putative advantage of the rationally developed azulene derivative 2 b over apomorphine.
Löber
Stefan
S
Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, 91052 Erlangen, Germany.
Tschammer
Nuska
N
Hübner
Harald
H
Melis
Maria Rosaria
MR
Argiolas
Antonio
A
Gmeiner
Peter
P
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D052176:Azulenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D017354:Point Mutation; D011485:Protein Binding; D051381:Rats; D050638:Receptors, Dopamine D4 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*
D052176:Azulenes; D008024:Ligands; D050638:Receptors, Dopamine D4; C005525:azulene; D001058:Apomorphine