Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin transporter. Part 4: 3-Alkyl-4-halo-6-nitroquipazines.

On the basis of the structure-activity relationship (SAR) of 4-chloro-6-nitroquipazine (Ki = 0.03 nM) and 3-fluoropropyl-6-nitroquipazine (Ki = 0.32 nM), 3-alkyl-4-halo-6-nitroquipazines were synthesized and tested for their potential abilities in vitro to displace [3H]citalopram binding to the rat cortical membranes. Binding affinities of 3b and 4d were Ki = 2.70+/-0.32 and 2.23+/-0.46 nM, respectively. The syntheses of 3-alkyl-4-halo-6-nitroquipazine, their in vitro binding affinities, and the SAR of C3, C4 position in 6-nitroquipazine are described.