High potent and selective arylpiperazine derivatives as ligands for the 5-HT1A receptor

This paper reports the synthesis and affinities on the 5-HT1A versus the α1A receptors of new arylpiperazinylalkylthiothienopyrimidine and thiadiazole derivatives 16–24. Arylpiperazines 16–23 show affinities values in the nanomolar range for the 5-HT1A receptor. The compound 16 is highly potent (Ki 0.26 nM, selectivity 28), the derivatives 20 and 21 are less potent, but highly selective (Ki9.40 and 5.06 nM, selectivity 207 and 73, respectively). Scheme 1. Reagents and conditions: (i) CSCl2, CHCl3/H2O, NaHCO3, room temperature; (ii) N2H4.H2O, CHCl3, room temperature; (iii) KOH, EtOH, reflux; (iv) HCl, H2O, room temperature; (v) 1-(3-chloropropyl)-4-(2-methoxyphenyl, 2-nitrophenyl or 2-pyrimidinyl)piperazine, EtOH, reflux.