ChemInform Abstract: High Affinity and Selectivity of [[(Arylpiperazinyl)alkyl]thio]thieno[2,3‐d]pyrimidinone Derivatives for the 5‐HT_1A Receptor. Synthesis and Structure—Affinity Relationships.

Abstract

High Affinity and Selectivity of [[(Arylpiperazinyl)alkyl]thio]thieno [2,3-d]pyrimidinone Derivatives for the 5-HT 1A Receptor. Synthesis and Structure-Affinity Relationships.-Modifications performed on the lead thienopyrimidinone refer in particular to: 1) the variation of substituents of the thienopyrimidine nucleus and the substitution of the thienopyrimidine system; 2) the substitution of the amino group of the pyrimidine ring and 3) the substitution on the piperazine ring of the orthomethoxyphenyl nucleus. The affinity of the new pyrimidinones like (V), (IX), and (XV) for 5-HT 1A receptors and the selectivity versus α 1 A receptors are studied. The importance of the non-pharmacophoric thienopyrimidine portion for affinity and selectivity towards 5-HT 1A receptor is obvious. Compound (Va), structurally related to the lead compound, and the isosteric pyridopyrimidinone (IX) show the highest affinity and selectivity.