Abstract
The synthesis and SAR for a novel series of 2-alkyl-4-aryl-tetrahydro-pyrido-pyrimidines and 2-alkyl-4-aryl-tetrahydro-pyrimido-azepines is described. Representative compounds were shown to be subtype selective 5-HT(2A) antagonists. Optimal placement of a basic nitrogen relative to the pyrimidine and the presence of a 4-fluorophenyl group in the pyrimidine 4-position was found to have a profound effect on affinity and selectivity.
MeSH terms
-
Animals
-
Azepines / chemical synthesis
-
Azepines / pharmacology*
-
Binding, Competitive
-
CHO Cells
-
Cricetinae
-
Cricetulus
-
Humans
-
Mice
-
Molecular Structure
-
NIH 3T3 Cells
-
Pyrimidines / chemical synthesis
-
Pyrimidines / pharmacology*
-
Radioligand Assay
-
Receptor, Serotonin, 5-HT2A / metabolism
-
Receptor, Serotonin, 5-HT2B / metabolism
-
Receptor, Serotonin, 5-HT2C / metabolism
-
Serotonin 5-HT2 Receptor Antagonists*
-
Serotonin Antagonists / chemical synthesis
-
Serotonin Antagonists / pharmacology*
-
Structure-Activity Relationship
Substances
-
Azepines
-
Pyrimidines
-
Receptor, Serotonin, 5-HT2A
-
Receptor, Serotonin, 5-HT2B
-
Receptor, Serotonin, 5-HT2C
-
Serotonin 5-HT2 Receptor Antagonists
-
Serotonin Antagonists