In our previous studies on the pirydo[1,2-c]pyrimidines we obtained a series of new compounds with dual SSRI and 5-HT_1A agonist activity. As a continuation of our research programme to develop faster acting antidepressants, we synthesized new derivatives of 4-aryl-5,6,7,8-tetrahydro-pyrido[1,2-c]pyrimidines with 3-(piperidin-4-yl)-1H-indole moiety.
The structures of new compounds were confirmed by ¹H and ¹³C NMR spectral data as well as by C, H, N analyses.
Target compounds were tested for their affinity for 5-HT_1A receptor and 5-HT reuptake inhibition using radioligand binding assay. Compounds 8a-k revealed affinity for 5-HT_1A receptor which varied from high to moderate (K_{i 5-HT1A}: 10,4 – 53,8 nM), while compounds 8l-t were almost inactive. Compounds 8a-t displayed moderate to low affinity for 5-HT-T receptor (K_{i 5-HT-T}: 71,6 – 943,7nM).
Compounds 8a(20mg/kg), 8d (20mg/kg), 8f (10mg/kg) and 8g (10mg/kg) were found to be presynaptic 5-HT_1A receptor agonists in induced hypothermia test in mice, while compound 8b (20mg/kg) displayed presynaptic 5-HT_1A receptor antagonistic activity.
Compounds 8d(20mg/kg), 8f (10mg/kg) and 8g (10mg/kg) revealed their postsynaptic 5-HT_1A agonist activity in forced swimming test in mice.

R_1, R_2, R_3, R₄: 8a: H, CH₃, OCH₃, H; 8b: H, OCH₃, H, H; 8c: H, OCH₃, OCH₃, H; 8d: F, H, OCH₃, H; 8e: H, Cl, OCH₃, H; 8f: H, CH₃, H, H; 8g: F, H, H, H; 8h: CH₃, H, H, H; 8i: CH₃, H, OCH₃, H; 8j: H, F, OCH₃, H; 8k: Cl, H, H, H; 8l: F, H, H, CH₃; 8m: H, H, H, CH₃; 8n: OCH₃, H, H, CH₃; 8o: CH₃, H, H, CH₃; 8p: H, CH₃, H, CH₃; 8q: H, OCH₃, H, CH₃; 8r: H, Cl, H, CH₃; 8s: Cl, H, H, CH₃; 8t: H, F, H, CH₃;

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