CoMFA methodology in structure-activity analysis of hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives based on affinity towards 5-HT1A, 5-HT2A and alpha1-adrenergic receptors

Dorota Maciejewska; Teresa Zołek; Franciszek Herold

doi:10.1016/j.jmgm.2006.02.002

CoMFA methodology in structure-activity analysis of hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives based on affinity towards 5-HT1A, 5-HT2A and alpha1-adrenergic receptors

J Mol Graph Model. 2006 Nov;25(3):353-62. doi: 10.1016/j.jmgm.2006.02.002. Epub 2006 Mar 20.

Authors

Dorota Maciejewska¹, Teresa Zołek, Franciszek Herold

Affiliation

¹ Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Str., 02-097 Warsaw, Poland. domac@farm.amwaw.edu.pl

PMID: 16542863
DOI: 10.1016/j.jmgm.2006.02.002

Abstract

Structural features of the pyrido[1,2-c]pyrimidine derivatives with arylpiperazine moiety and their affinities towards 5-HT1A, 5-HT2A and alpha1-adrenergic receptors were analyzed using the CoMFA procedure. On the basis of 3D-QSAR models for the 5-HT2A and alpha1-adrenergic receptors, four compounds with expected better affinity/selectivity were proposed and synthesized. The affinities obtained confirm experimentally the usefulness of CoMFA models. Our results suggest that active conformations adopted by the studied molecules when interacting with the receptors are neutral instead of the protonated ones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Models, Molecular
Molecular Structure
Pyrimidines / chemistry*
Quantitative Structure-Activity Relationship*
Receptor, Serotonin, 5-HT1A / chemistry
Receptor, Serotonin, 5-HT2A / chemistry
Receptors, Adrenergic, alpha-1 / chemistry*
Spiro Compounds / chemistry*
Structure-Activity Relationship

Substances

Pyrimidines
Receptor, Serotonin, 5-HT2A
Receptors, Adrenergic, alpha-1
Spiro Compounds
octahydropyrido(1,2-c)pyrimidine
Receptor, Serotonin, 5-HT1A
spirobishexahydropyrimidine