Search for influence of spatial properties on affinity at α1-adrenoceptor subtypes for phenylpiperazine derivatives of phenytoin.
A series of phenylpiperazine derivatives of phenytoin was evaluated for their affinity at α(1)-adrenoceptor subtypes in functional bioassays (rat tail artery: α(1A) and/or α(1B); guinea pig spleen: α(1B); rat aorta: α(1D)). The most potent compounds at α(1A)-, α(1B)- and α(1D)-adrenoceptors, 11, 18 and 8, showed affinities in the submicromolar range. The role of a hydrogen bond donor group for affinity and selectivity at α(1B)-adrenoceptors, postulated by Bremner's pharmacophore model, was confirmed by functional and molecular modelling studies.
Handzlik
Jadwiga
J
Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Kraków, Poland.
Pertz
Heinz H
HH
Görnemann
Tilo
T
Jähnichen
Sven
S
Kieć-Kononowicz
Katarzyna
K
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D008958:Models, Molecular; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
D058668:Adrenergic alpha-1 Receptor Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D010672:Phenytoin; C031503:phenylpiperazine