Three-dimensional pharmacophore hypotheses were built from a set of 10 octopamine (OA) agonist 1-arylimidazole-2(3H)-thiones (AIHTs) and 1-arylimidazolidine-2-thiones (AITs). Among the ten common-featured models generated by program Catalyst/HipHop, a hypothesis including a hydrophobic aromatic (HpAr), three hydrophobic aliphatic (HpAl) and a hydrogen-bond acceptor lipid (HBAl) features was considered to be (important in evaluating the OA-agonist activity. Active OA agonist 2,6-Et)2 AIT mapped well onto all the HpAr, HpAl and HBAl features of the hypothesis. On the other hand, inactive compound (2,6-Et)2 AIHT was shown to be difficult to achieve the energetically favorable conformation which is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies on OA agonists demonstrate that an HpAr, three HpAls and an HBAl sites located on the molecule seem to be essential for OA-agonist activity.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry