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Three series of N-acyl and N-cyclohexyl- or N-methyl or N-phenyl-thioureas of 4-substituted (methyl, phenyl, 2-pyridyl)piperazines (4-12) were synthesised according to a highly convergent one-pot procedure and tested in vivo (local anaesthetic, anti-hyperlipoproteinemic, analgesic, anti-inflammatory, antiarrythmic activities) and in vitro (antiaggregating and, for some selected derivatives, antiproliferative activities) experiments. All the test compounds showed local anaesthesia in particular 4Ar(4), 5Ar(4), 12Ar(3) (after 5 min) and 5Ar(2), 5Ar(3), 9Ar(4) (after 30 min) were equipotent to lidocaine. In lowering triglyceride levels, compounds 6Ar(4) and 7Ar(3) were more active than nicotinic acid, whereas 7Ar(4) and 11Ar(4) were approximately equipotent. As concerns analgesic activity, 5Ar(2) and 5Ar(4) were as active as indomethacin. Appreciable anti-inflammatory activity was found in 8Ar(1), 5Ar(2) and 11Ar(2), but inferior to that of indomethacin. High levels of antiarrythmic activity, comparable with that of quinidine, were found in derivatives 4Ar(2) and 10Ar(1). Compounds 4Ar(2) and 8Ar(2), assayed in antitumor in vitro screening system at National Cancer Institute (NCI), showed significant antiproliferative activity against ACHN cell line (GI50: 0.13 microM) and NCI-H226 cell line (GI50: 1.03 microM), respectively.

The synthesis of N,N-disubstituted 3-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1-yl)-propanamides and -propanamines, starting from 4-benzoyloxy-3,5-diphenyl-1H-pyrazole, and of N-substituted 2-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1-yl)ethanamines, starting from 4-acetoxy-1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole, is described. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as moderate hypotensive, antiarrhythmic, local anesthetic, sedative and antiinflammatory activities in rats and mice.

A synthesis of esters from 1,2,3,3-tetramethyl-2-azabicyclo[2.2.2]octan-5-endo-ol lithium slat and acyl chlorides is described. A number of these compounds showed strong antiarrhythmic, local anesthetic and hypotensive activities.