An improved nicotinic pharmacophore and a stereoselective CoMFA-model for nicotinic agonists acting at the central nicotinic acetylcholine receptors labelled by [3H]-N-methylcarbamylcholine
Abstract
A study of a series of compounds with agonistic effect at the α4β2 nicotinic acetylcholine receptors resulted in an improved pharmacophore model as well as a CoMFA model. The pharmacophore was composed of three pharmacophoric elements: (1) a site point ( a) corresponding to a protonated nitrogen atom, (2) a site point ( b) corresponding to an electronegative atom capable of forming a hydrogen bond, and (3) the centre of a heteroaromatic ring or a C=O bond ( c). The pharmacophoric elements were related by the following parameters: ( a-b) 7.3-8.0 Å, ( a-c) 6.5-7.4 Å, and the angle between the two distance vectors (Δ bac) 30.4-35.8°. In addition to this, a stereoselective CoMFA model was developed, which showed good predictability even for compound classes not present in the training set.
- Publication:
-
Journal of Computer-Aided Molecular Design
- Pub Date:
- March 2001
- DOI:
- 10.1023/A:1008140021426
- Bibcode:
- 2001JCAMD..15..247T
- Keywords:
-
- CoMFA model;
- 3D-QSAR;
- nicotinic agonists;
- pharmacophore model