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.
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.
Maciejewska
Dorota
D
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Str., 02-097 Warsaw, Poland. domac@farm.amwaw.edu.pl
Zołek
Teresa
T
Herold
Franciszek
F
D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry*; D013141:Spiro Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
D011743:Pyrimidines; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D013141:Spiro Compounds; C483405:octahydropyrido(1,2-c)pyrimidine; D044282:Receptor, Serotonin, 5-HT1A; C080175:spirobishexahydropyrimidine