Search

The title compounds were synthesized by cyclizing 3-dimethylaminomethylene-4-chromanone with creatine to give the acid 2 that was successively converted into the corresponding amides 3a-f via diphenylphosphorylazide and the relevant amines. The free acid 2 and some of 3a-f showed antiinflammatory, hypotensive and antiarrhythmic properties.

The synthesis of novel 2-aryl-3-phenylamino-4,5-dihydro-2H-benz[g]indazoles 4a-f, starting from N-phenyl-3,4-dihydro-1(2H)-oxonaphthalene-2-carbothioamide and the proper arylhydrazines, is described. Title compounds were evaluated for antiinflammatory, analgesic, antipyretic, antiarrhythmic, hypotensive, local anaesthetic and platelet antiaggregating activities; some of them showed an appreciable antiarrhythmic activity in rats and a good level of infiltration anaesthesia in mice.

The synthesis of 5-[[omega-(dialkylamino)alkoxy]methylene]-1,3,3-trimethyl-2- oxabicyclo[2.2.2]octan-6-ones by reaction of (+)-5-(hydroxymethylene)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan- 6-one with a series of omega-(chloroalkyl)dialkylamines in the presence of potassium carbonate is described. Some compounds showed strong hypotensive, local anesthetic and antiarrhythmic activity in rats and mice, as well as moderate analgesic, antipyretic and in vitro platelet antiaggregating activity.

The synthesis of (+)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one O-[omega-(dialkylamino)alkyl]oximes by reaction of (+)-camphoroxime sodium salt with a series of omega-(chloroalkyl)dialkylamines in DMF solution is described. Some of the above compounds showed strong hypotensive, antiinflammatory, analgesic and local anesthetic activity in rats and mice, as well as moderate antiarrhythmic, antipyretic and in vitro platelet antiaggregating activity.

The synthesis of 4-amino-3,5-diphenyl-1H-pyrazole-1-ethanol, as well as of their N-methyl, N-ethyl and N,N-dimethyl derivatives is described. A series of 1-(2-alkylaminoethyl)-3,5-diphenyl-1H-pyrazole-4-amines and of N-substituted 4-dimethylamino-3,5-diphenyl-1H-pyrazole-1-ethanamines were also prepared. Some of the above compounds showed remarkable local anesthetic, analgesic and in vitro platelet antiaggregating activities, as well as moderate antiinflammatory and antipyretic activities in rats and mice.

The synthesis in excellent yields of 2,3-dihydro-6-mercapto-1,3,5-triphenyl-2-thioxo-4(3H)-pyrimidinone 3 and 5-ethoxycarbonyl-2,3-dihydro-6-mercapto-1,3-diphenyl-2-thioxo-4(3H )- pyrimidinone 4 by reaction of methyl phenylacetate or diethyl malonate, respectively, with phenyl isothiocyanate (3 molar equivalents) and sodium hydride (2 molar equivalents) in DMF solution is described. Acylation of 3 and 4 with acyl chlorides gave, generally in satisfactory yields, 6-acylthio derivatives 13 and 14. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as remarkable antiinflammatory, antiarrhythmic, local anesthetic and antihyperlipidemic activities in rats and in mice. Weak anticonvulsant and hypoglycemic activities were also detected.

The synthesis of N-substituted 4,5(3)-diphenyl-3(5)-pyrazoleamines by reaction of N-substituted 3-oxo-2,3-diphenylpropane-carbothioamides with hydrazine is described. Some compounds showed remarkable antipyretic, antiarrhythmic and hypotensive activity in rats, as well as weak antiinflammatory, analgesic and in vitro platelet antiaggregating activity.

A series of N-acyl-4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides was prepared in excellent yields by reaction of 4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides with a number of aromatic or heterocyclic acyl chlorides in dry pyridine solution and in the presence of sodium hydride. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid; moreover, some compounds exhibited moderate analgesic, antiinflammatory and hypotensive activities in mice or rats.

The synthesis of a series of N-substituted O-(3-amino-2-hydroxypropyl)oximes of 1,3,3-trimethyl-5-endo-(1-piperidinyl or 4-morpholinyl)-2-oxabicyclo [2.2.2]octan-6-ones is described. Some of these ethers showed strong local anesthetic activity in mice and platelet antiaggregating activity in vitro comparable to that of acetylsalicylic acid, as well as moderate hypotensive, antiarrhythmic and analgesic activities in rats and mice.

The syntheses of 1-(2-hydroxypropyl)-3,5-diphenyl-1H-pyrazole 1 by reaction of 1-hydrazino-2-propanol with dibenzoylmethane and of N-substituted 1-(2-aminopropyl)-3,5-diphenyl-1H-pyrazoles 3 by reaction of primary and secondary amines with the tosylate of 1, as well as of N-substituted 1-(3-amino-2-hydroxypropyl)-3,5-diphenyl-1H-pyrazoles 6 starting from 3,5-diphenyl-1H-pyrazole, are described. Some compounds 3 and 6 showed remarkable antiinflammatory activity in rats, as well as weak analgesic, antipyretic, antiarrhythmic, hypotensive activities in mice and rats and moderate platelet antiaggregating effects in vitro.

The synthesis of 6-cis-dimethylamino-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-trans-ol (III) starting from 1,3,3-trimethyl-6-nitrimino-2-oxabicyclo[2.2.2]octane is described. Starting from aminoalcohol (III), a series of N-substituted urethanes (IV) and esters (V), as well as the rigid analogue of acetylcholine (VII), were prepared. A number of compounds (V) and particularly (IV) showed remarkable hypotensive and bradycardic activities in rats, whereas the p-aminobenzoate (V h) showed infiltration anesthesia in mice comparable to that of lidocaine. Antiarrhythmic activity in mice and antiacetylcholine activity in vitro are also reported.

The synthesis of two series of N-substituted 4,7,7-trimethyl-3-(1-piperidinyl)bicyclo[2.2.1]hept-2-ene 2-carboxamides (I d-h) and 2-carbothioamides (I i-o), as well as of some N-aryl 4,7,7-trimethyl-3-(1-pyrrolidinyl)bicyclo[2.2.1]hept-2-ene 2-carboxamides (I a-c), by reaction of camphor piperidinoenamine and pyrrolidinoenamine with aryl isocyanates and isothiocyanates is described. On the whole compounds (I d-h) showed a weak hypotensive activity in rats.

The synthesis of 2-substituted 4-phenyl-5-(3,5-diphenyl-1H-pyrazol-1-yl)pyrimidines 4 a-e by reaction of 1-(1-dimethylaminomethylene-2-oxo-2-phenylethyl)-3,5-diphenyl-1H-pyrazol e with acetamidine, benzamidine, guanidine, guanidinaecetic acid and creatine, respectively, is described. The alpha-aminoacid derivatives 4 d and 4 e gave a series of amides 7 by coupling with primary or secondary amines in dimethylformamide (DMF) solution in the presence of diphenyl-phosphorylazide (DPPA) and triethylamine. Some compounds 4 and 7 showed a platelet antiaggregating activity in vitro superior or comparable to that of acetyl-salicylic acid, as well as moderate antihypertensive, local anesthetic, analgesic and antiinflammatory activities in rats and mice.

Some aliphatic and aromatic esters 2a–l were prepared starting from 5-aryl-1,2,4-triazoline-3-thiones bearing a 2-hydroxyethyl chain in position 2. The title compounds were evaluated for antipyretic and anti-inflammatory activities. Nearly all derivatives and in particular 2f , 2h , 2k exhibited antiphlogistic properties but were lacking in antipyretic activity.

Two series of N-[5-oxo-4-(arylsulfonyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]-amides were synthesized and tested in vivo for their analgesic and anti-inflammatory activities. All the new compounds possess good antalgic action in the acetic acid writhing test and some terms of the series showed also fair anti-inflammatory activity in the carrageenan rat paw edema test. Ulcerogenic and irritative action on the gastrointestinal mucose, in comparison with indomethacin is low.

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.

A series of omega-dialkylaminoalkyl esters of N-phenyl aminethiocarboximidic acids was prepared by reaction of N-phenyl 1-pyrrolidine, 1-piperidine, 4-morpholine, 1,2,3,4-tetrahydro-1-quinoline, 1,2,3,4-tetrahydro-2-isoquinoline, 10-phenothiazine, N-phenyl-2-pyridylamine and N-benzyl-2-pyridylamine-carbothioamides (prepared in situ from the appropriate secondary amine and phenyl isothiocyanate) with a number of omega-chloroalkyldialkylamines in anhydrous DMF or THF solution in the presence of sodium hydride. Good yields of the above esters were obtained provided that sodium hydride was added initially or after the formation of 3,3-disubstituted 1-phenylthiourea, according to the nature of the secondary amine. Some esters showed in mice local anesthetic activity comparable with that of lidocaine, as well as moderate hypoglycemic, antiarrhythmic, analgesic, antiacetylcholine, H1-antithistamine and platelet antiaggregating activities.

A series of omega-dialkylaminoalkyl esters of 3-dialkylamino-4,7,7-trimethyl-N-phenylbicyclo[2.2.1]hept-2-ene-2- iminothiolic acids 3 was prepared by reaction of 4,7,7-trimethyl-3-(dimethylamino or 1-piperidinyl)-N-phenylbicyclo[2.2.1] hept-2-ene-2-thiocarboxamides with a number of omega-chloroalkyldialkylamines in the presence of sodium hydride in DMF or benzene solution. Some esters 3 showed an appreciable local anesthetic activity in mice.

The synthesis of N-substituted 1-(2-aminoethyl)-3,5-diphenyl-1H-pyrazoles and their 4-bromo derivatives (V) by reaction of primary and secondary amines with the tosylates of 1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole and its 4-bromo derivative is described. Some of compounds (V) showed a remarkable analgesic activity in mice. Moreover, the above compounds usually exhibited moderate hypotensive, bradycardiac and antiinflammatory activities in rats, infiltration anesthesia in mice, as well as a weak platelet antiaggregating activity in vitro.

Lithium aluminium hydride reduction of N-phenoxycarbonyl-N,N-(1,3,3-trimethylbicyclo[2.2.1]-hept-2- yl)benzamidine (II), which afforded the N-acyl derivatives (III a-f) in good yields. Compounds (II) and (III) showed a moderate hypotensive activity in rats. Local anesthetic activity by infiltration in mice, effects on heart rate and antiarrhythmic activity in rats are also reported.

The synthesis of title compounds by reaction of fenchone nitrimine with 2-aminoethanol and 3-aminopropanol, followed by stereospecific NaBH4 reduction of the resulting imines, Eschweiler-Clarke reductive methylation and esterification with aliphatic and aromatic acyl chlorides is described. Some esters showed an appreciable hypotensive activity in rats. Effects on heart rate and antiarrhythmic activity in rats, as well as infiltration anesthesia in mice, are also reported.

The synthesis of title compounds by reaction of camphor nitrimine with 2-amino-2-methylpropanol, followed by NaBH4 reduction of the resulting imine to the aminoalcohol (III) and esterification of (III) with aliphatic and aromatic acyl chlorides in pyridine solution, is described. Phenyl carbamate (V) was also prepared by reaction of (III) with phenyl isocyanate. Some esters and (V) showed a moderate hypotensive activity in rats. Effects on heart rate and antiarrhythmic activity in rats, as well as infiltration anesthesia in mice, are also reported.

The synthesis of 1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole (II) and its 4-bromo derivative (III) starting from chalcone epoxide, as well as of a series of esters and N-substituted carbamates derived from (II) and (III), is described. Some of these compounds showed remarkable depressant, antiarrhythmic and analgesic activities in mice and rats. Moreover, the above compounds usually exhibited moderate hypotensive, bradycardic and antiinflammatory activities in rats, infiltration anesthesia and hypoglycemic activity in mice, as well as a weak platelet antiaggregating activity in vitro.

The synthesis of beta-dialkylaminoethyl ethers (II a-f) and gamma-dialkylaminopropyl ethers (II g-i), as well as of aryl carbamates (III 1, m), starting from (+)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-hydroxyimine (I), is described. beta-Dimethylaminoethyl ether (II a) showed a remarkable hypotensive and bradycardic activity in rats; moreover, nearly all compounds (II) and (III) exhibited a weak antiarrhythmic activity in rats. Infiltration anesthesia in mice, beta-blocking activity in dogs and antiacetylcholine activity in vitro are also reported.