Synthesis and conformational analysis of 3-substituted derivatives of 1H, 3H-pyrido[2,3-d]pyrimidin-4-one of expected depressive activity on central nervous system. Part II.

Two series of new 1-aryl piperazinylacetyl derivatives of 1H, 3H-pyrido[2,3-d]pyrimidyn-4-one were synthesized. The compounds were prepared by chloroacetylation; when made to react with respective arylpiperazine, then yielded VIa-o. The structures of compounds VIa-o were analyzed by 1H and 13C NMR spectroscopy. For selected compounds, acute toxicity and anticonvulsant activity were determined.

Analgesic activity and opiate receptor affinity of new derivatives of N-butylpiperidine.

The three newly synthesized derivatives of N-butylpiperidine 1-butyl-4-phenyl-4-isonicotinoylaminoethylpiperidine (BG 25), 1-buty-isonicotinoylpiperidine (BG 26) and N-(1-butyl-4-phenyl-4-piperidinoyl) tetrahydropapaverine (BG 9) were evaluated for analgesic activity and opiate receptor affinity. All the three compounds showed analgesic activity both in hot-plate and flinch-squeak-jump test in mice, BG 9 being the most potent. The affinity of the compounds to opiate receptor was moderate (in comparison with pentazocine): the affinity of BG 9 was much greater than that of BG 25 and BG 26. The compounds showed a pronounced inhibitory action in stimulated guinea-pig ileum preparation; this was reversible by naloxone. As evaluated on pA basis, all three investigated compounds showed moderate antagonistic activity. Also in this respect BG 9 was more active than the other two compounds. Cholinolytic and strong spasmolytic properties were observed in isolated rat ileum preparation for BG 9 only.