Daniel Bozsing

Synthesis and pharmacological study of new 3,4-dihydro-2H,6H-pyrimido-[2,1-b][1,3]thiazines

Summary A series of racemic pyrimido-thiazine derivatives was synthesized and many of their in vivo activities found to be comparable to acetylsalicylic acid and aminophenazone in an antiinflammatory model and an antipyretic test. Analogues 7a and 7e are the most potent in rat carrageenin and yeast fever assays. These compounds did not inhibit prostaglandin biosynthesis in vitro.

Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist.

Our aim was to specify the 5-HT2 subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT2B ligand, in receptor binding studies and characterize its pharmacology at 5-HT2A, 5-HT2B and 5-HT2C receptors in in vivo experiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT2B receptors (pKi = 9.0) but much weaker affinity for 5-HT2A and 5-HT2C receptors (pKi = 6.2 and 7.7, respectively). In the classic 5-HT2B test, EGIS-7625 produced a concentration-related parallel rightward shift in the concentration-response relationship for the 5-HT-induced smooth muscle constriction in rat stomach fundus strips with a pA2 of 9.4. On the other hand, EGIS-7625 was a weak competitive antagonist at 5-HT2A receptors as it shifted 5-HT-induced concentration-response curves to the right at high concentrations (pA2 = 6.7) in rabbit pulmonary artery strips. The m-chlorophenylpiperazine-induced hypomotility and hypophagia was only partially attenuated by EGIS-7625 even at a dose of 30 mg/kg i.p. while mianserin, a non-selective 5-HT antagonist was almost fully effective in these tests at 3 mg/kg i.p., suggesting weak antagonistic effect of EGIS-7625 at neuronal 5-HT2C receptors, in vivo. In conclusion, EGIS-7625 is a potent, selective and competitive 5-HT2B antagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-HT2A and 5-HT2B receptors.

Synthesis of α-(trifluoromethyl)phenylacetonitrile. Anomalous reactions of α-tosyloxy-α-(trifluoromethyl)phenylacetonitrile with sodium borohydride

Abstract The hitherto unknown α-(trifluoromethyl)phenylacetonitrile has been synthesized by reduction of the cyanohydrin of α,α,α-trifluoroacetophenone. Sodium borohydride reduction of the corresponding cyanohydrin tosylate resulted in reductive decyanation in dimethyl sulphoxide and in reduction of the nitrile group in t-butanol.

Synthesis and evaluation of 5-HT2A and 5-HT2C receptor binding affinities of novel pyrimidine derivatives

In an effort to find potential anxiolytic and/or antipsychotic agents with selective 5-HT(2C) affinity a series of new pyrimidine derivatives was prepared and the binding affinities for 5-HT(2A) and 5-HT(2C) receptors were determined.