Three-dimensional common-feature hypotheses for octopamine agonist arylethanolamines.
Three-dimensional pharmacophore hypotheses were built from a set of 12 octopamine (OA) agonist arylethanolamines (AEAs). Among the 10 common-featured models generated by program catalyst/HipHop, a hypothesis including a hydrogen-bond donor (HBD) and a hydrogen-bond acceptor lipid (HBA1) features was considered to be important in evaluating the OA activity. OA mapped well onto all the HBD and HBA1 features of the hypothesis. On the other hand, for some inactive compounds, their lack of affinity is primarily due to their inability to achieve an energetically favorable conformation shared by the active compounds. Taken together, structures of a 4-OH-Ph, alpha-OH, and a primary amine are important for OA activities. The present studies on OA agonists demonstrate that an HBD and an HBA1 sites located on the molecule seem to be essential for OA activity.
Hirashim
Akinori
A
Department of Applied Genetics and Pest Management, Faculty of Agriculture, Graduate School, Kyushu University, Fukuoka, Japan. ahirasim@agr.kyushu-u.ac.jp
Morimoto
Masako
M
Kuwano
Eiichi
E
Taniguchi
Eiji
E
Eto
Morifusa
M
D000316:Adrenergic alpha-Agonists / Q000737:chemistry*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015195:Drug Design; D004983:Ethanolamines / Q000138:chemical synthesis* / Q000737:chemistry*; D005260:Female; D006860:Hydrogen Bonding; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009655:Octopamine / Q000819:agonists* / Q000737:chemistry; D010526:Periplaneta / Q000737:chemistry
D000316:Adrenergic alpha-Agonists; D004983:Ethanolamines; D009655:Octopamine; D000242:Cyclic AMP