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The synthesis of some N,N-disubstituted 4-amino-5,6,7,8,9,10-hexahydro-3- phenyl-2H-cycloocta[b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylenecyclooctanones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. The dimethylamino derivative showed a local anesthetic activity in mice superior to that of lidocaine, and some compounds exhibited a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak antiarrhythmic and antiinflammatory activities in rats. more...

The synthesis of ethyl esters of 5-cyano-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids carrying as 2-substituent the 2-,3- or 4-pyridyl group is described. By alkaline hydrolysis followed by acidification, these esters gave the corresponding carboxylic acids, which were decarboxylated to 1,2-dihydro-2-oxo-6-(2,3,4-pyridyl)-3-pyridinecarbonitriles. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea-pigs. Ethyl 5-cyano-1,6-dihydro-6-oxo-2-(2-pyridyl)-3-pyridinecarboxylate showed an appreciable positive inotropic activity, although inferior to that of milrinone; moreover, some other compounds bearing the above 2-substitution pattern showed interesting antiinflammatory, analgesic and hypotensive activity. more...

The synthesis of some O-(2-dialkylaminoethyl)oximes of 5-[(4-methoxy- or 4-methylthiophenyl)methylene]-1,3,3-trimethyl-2-oxabicyclo[2.2.2] octan-6-ones 5 by reaction of the corresponding oximes as sodium salts with the appropriate 2-chloroethyldialkylamine in dry ethanol solution is described. Some aminoethers 5 showed appreciable hypotensive and antiarrhythmic activities in rats, as well as a weak platelet antiaggregating activity in vitro and a moderate infiltration anesthesia in mice. more...

Reaction of methyl 4-methoxy-2-dimethylaminomethylene-3-oxobutanoate with arylhydrazines gave methyl 1-aryl-5-(methoxymethyl)-1H-pyrazole-4-carboxylates 1 in high yields. Esters 1 were hydrolyzed to the relative carboxylic acids, which were converted by heating to 1-aryl-5-(methoxymethyl)-1H-pyrazoles 3 in good yields. Reaction of 3 with hydrobromic acid afforded the intermediate 1-aryl-5-(bromomethyl)-1H-pyrazoles, which were converted with potassium cyanide to 1-aryl-1H-pyrazole-5- acetonitriles, whose hydrolysis gave the required 1-aryl-1H-pyrazole-5-acetic acids. Some acids 5 showed a strong antiinflammatory and analgesic activity in rats and mice, respectively, as well as moderate antipyretic and in vito platelet antiaggregating effects. more...

In a new series of milrinone analogues (esters of 2-substituted 5-acetyl-1,6-dihydro-6-oxo-3-pyridinecarboxylic acids), ethyl 5-acetyl-1,6-dihydro-6-oxo-2-phenyl-3-pyridinecarboxylate (compound 2f) has been found to be more potent and more effective than milrinone as a positive inotropic agent while affecting only marginally the frequency rate of guinea-pig isolated atria. This finding prompted us to study the mechanism of cardiac action of compound 2f in electrically driven left atrium from reserpine-treated guinea pigs. Compound 2f induced a statistically significant increase in the contractile force at a concentration as low as 1 microM, while the minimum effective concentration of milrinone was 10 microM. The beta-blocker propranolol (0.1 microM) caused a marked inhibition of the inotropic effect of compound 2f. Adenosine deaminase (1 and 2 U/ml) inhibited significantly and in a concentration-dependent manner the increase in inotropism induced by compound 2f and the adenosine deaminase-resistant response was abolished by 0.1 microM propranolol. In the presence of 0.1 microM propranolol, compound 2f (5 to 30 microM) antagonised in competitive manner the negative inotropic effect induced by N6-(R-phenylisopropyl) adenosine (R-PIA) (0.01-1.0 microM), a stable adenosine receptor agonist. Schild regression analysis gave in fact a slope of 1.02 +/- 0.06 and the pA2 value for compound 2f was 5.41 +/- 0.28. Compound 2f also inhibited phosphodiesterase (PDE) III isolated from calf heart, this inhibition being quantitatively significant only at the highest concentrations tested (0.5 M to 1 mM).(ABSTRACT TRUNCATED AT 250 WORDS) more...

The synthesis of ethyl or methyl 6-substituted 3-(benzoylamino)-2-oxo-2H-pyran-5-carboxylates 2 and 3-(benzoylamino)-7,8-dihydro-2H-1-benzopyran-2,5(6H)-diones 4 by reaction of hippuric acid in acetic anhydride with ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates and 2-dimethylaminomethylene-1,3-cyclohexanediones, respectively, is described. Some compounds 2 and 4 showed a strong local anesthetic activity in mice and a platelet antiaggregating activity in vitro comparable to that of acetylsalicylic acid, as well as moderate analgesic, antiinflammatory and antiarrhythmic activities in rats and mice. more...

The synthesis of some 5-substituted 4-isoxazoleacetic acids starting from 5-substituted 4-isoxazolemethanols via their conversion to 4-(bromomethyl)isoxazoles, 4-isoxazoleacetonitriles and acid hydrolysis of the latter is described. 5-Ethyl- and 5-propyl-4-isoxazoleacetic acids showed in the writhing test an analgesic activity comparable to that of aspirin. more...

A series of 5-(arylmethylene)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6- ones was prepared by reaction of (+)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one with aromatic aldehydes in an alkaline medium. These compounds can be considered as potential UVB or UVA sunscreens. In vitro phototoxicity tests (photohemolysis and Candida albicans) showed that they exhibit in general a low phototoxicity level. more...

The synthesis of some N,N-disubstituted 4-amino-5,6,7,8-tetrahydro-3,6- diphenyl-2H-1-benzopyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylene-4-phenylcyclohexanones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid and an appreciable antiarrhythmic activity, as well as weak anti-inflammatory and local anesthetic activities in rats and mice. more...

The synthesis of N-aryl-5(3)-phenyl-4-(3,5-diphenyl-1-pyrazolyl)-3(5)- pyrazoleamines 3 by reaction of some N-aryl-3-oxo-3-phenyl-2-(3,5-diphenyl-1- pyrazolyl)propanecarbothioamides with hydrazine is described. Also prepared were 4,5-dihydro-3-phenyl-4-(3,5-diphenyl-1-pyrazolyl)-1H-pyrazoles 6 and 1,6-dihydro-4-phenyl-5-(3,5-diphenyl-1-pyrazolyl)pyrimidines 7 by reaction of 1-phenyl-2-(3,5-diphenyl-1-pyrazolyl)-2-buten-1-one with hydrazine or guanidine and benzamidine, respectively. Some compounds 3, 6 and 7 showed remarkable antipyretic, antiinflammatory and in vitro platelet antiaggregating activities, as well as weak analgesic, antiarrhythmic, hypotensive and local anesthetic activities in rats and mice. more...

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. more...

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. more...

The synthesis of a series of N-substituted 4-carboxy-1-phenyl-1H-pyrazole-5-propanamides by reaction of 1-phenyl-1H-oxepino[4,3-c]pyrazole-4(8H),6(7H)-dione with aromatic primary amines is described. Some amides showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as moderate antiinflammatory, analgesic and antipyretic activities in rats or mice. more...

The synthesis of ethyl or methyl 4-substituted or unsubstituted 2-methylthio-5-pyrimidinecarboxylates 3 a-i and 8 o mainly by reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with 2-methylisothiourea is described. Also some ethyl 2-substituted (NH2, CH3, C6H5) 4-trifluoromethyl-5-pyrimidinecarboxylates were prepared. Some of the above esters were hydrolyzed to the relative carboxylic acids, which were decarboxylated to the corresponding 2,4-disubstituted pyrimidines. Esters 3 a-i and 8 o were tested for their toxicity on Vero cultured cells and for their inhibitory activity against herpes simplex virus type 1 (HSV-1) infectivity in a short-term plaque assay. At non toxic concentrations, each ester was found to be active, the most interesting compound being 3 h, which achieved a 80.9% inhibition of HSV-1 infectivity at 12 micrograms/ml. Moreover, esters 3 f, 8 l and acid 9 o were active against some fungal strains. more...

The synthesis of a series of 1-aryl-1,6-dihydro-4H-thieno[3,4-c]pyrazol-4-ones by cyclization of 3-[(2-arylhydrazino)methylene]thiophene-2,4(3H,5H)-diones, prepared by reacting 3-dimethylaminomethylenethiophene-2,4(3H,5H)-dione with arylhydrazines, is described. The 4-fluorophenyl derivative showed remarkable analgesic, antiinflammatory and antipyretic activities in mice or rats, as well as a platelet antiaggregating activity in vitro comparable to that of acetylsalicylic acid. more...

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. more...

The synthesis of [(1-methyl-1H-indazol-4-yl)oxy]acetic acid 4, 1-methyl-1H-indazole-4-acetic acid 9, 2-(1-methyl-1H-indazol-4-yl)propanoic acid 15 and [[(1,5,6,7-tetrahydro-1-methyl-4H-indazol-4-ylidene)amino]oxy]acet ic acid 16, as well as of amides and esters derived from 4 and 9, starting from 1,5,6,7-tetrahydro-1-methyl-4H-indazol-4-one is described. Some of the above compounds showed weak antiinflammatory, analgesic, antipyretic and hypotensive activities in rats and mice, as well as moderate platelet antiaggregating effects in vitro. more...

The synthesis of ethyl or methyl esters of 5-cyano-1,6-dihydro-6-oxo-3- pyridinecarboxylic acids carrying as 2-substituent a polar group such as CO2C2H5, (CH2)2CO2CH3, (CH2)3CO2C2H5, CH2OCH3, or CF3 group is described. Also 2-[5-cyano-1,6-dihydro-2-(1,1-dimethylethyl)-6-oxo-3-pyridyl]-2- oxoacetic acid and 2,5,6,8-tetrahydro-2,5-dioxo-1H-thiopyrano[3,4-b]pyridine-3-carbon itrile were prepared. Nearly all the above esters gave routinely the corresponding carboxylic acids by alkaline hydrolysis followed by acidification. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea-pigs. 5-Cyano-2-trifluoromethyl-1,6- dihydro-6-oxo-3-pyridinecarboxylic acid and, in a lesser degree, the relative ethyl ester showed an appreciable positive inotropic activity, although inferior to that of milrinone. more...

The synthesis of 4-hydroxy-1-phenyl-1H-indazole-5-acetic acid 5 4-methoxy-1-phenyl-1H-indazole-5-yl-acetic acid 7 and 5-benzyl-1-phenyl-1H-indazol-4-ol 8, starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one, is described. These compounds showed in mice an analgesic activity superior to that of acetylsalicylic acid and comparable to that of dipyrone; moreover, compound 5 exhibited an appreciable anti-inflammatory activity in rats. Grossbehavioral effects and acute toxicity in mice are also reported. more...

The synthesis of some N,N-disubstituted 4-amino-6,7,8,9-tetrahydro-3-phenylcyclohepta[b]pyran-2(5H)-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 2-aminomethylenecycloheptanones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak local anesthetic, antiinflammatory and analgesic activities in mice and rats. more...

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. more...

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. more...

The synthesis of a series of 5-substituted 4-isoxazolecarboxamides by reaction of eight 5-substituted 4-isoxazolecarbonyl chlorides with pyrrolidine, piperidine, morpholine and 4-trifluoromethylaniline is described. Some of these amides showed platelet antiaggregating activity in vitro slightly inferior to that of acetylsalicylic acid, as well weak antiinflammatory, analgesic and antipyretic activities in rats and mice. more...

The synthesis of esters derived from 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-endo-ol, obtained by LiAlH4 reduction of 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-one, is described. Some of these esters showed an appreciable antiarrhythmic activity in rats, as well as moderate hypotensive and local anesthetic activities in rats and mice, respectively. more...

The synthesis of 5-[4-(omega-dialkylaminoalkoxy)phenylmethylene]- 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ones 3 by reaction of some 4-(omega-dialkylaminoalkoxy)benzaldehydes with (+)-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-one in the presence of sodium methoxide is described. Some aminoethers 3 showed platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak antiarrhythmic activity in rats and moderate infiltration anesthesia in mice. more...

The synthesis of some N,N-disubstituted 4-amino-6,7-dihydro-3-phenylbenzo[6,7]cyclohepta[1,2-b]pyran-2(5H) -ones by reaction of phenylchloroketene with a series of N,N-disubstituted 6-aminomethylene-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as a weak local anesthetic activity in mice and antiinflammatory activity in rats. more...

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. more...

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-pyrano[3,2-d]-1-benzoxepin-2 -ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a platelet antiaggregating activity in vitro slightly superior to that of acetylsalicylic acid, as well as weak local anesthetic and antiinflammatory activities in mice and rats, respectively. more...

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3,8-diphenyl-2H-pyrano[2,3-f]quinazolin- 2-ones by the reaction of phenylchloroketene with a series of N,N-disubstituted (E)-6-aminomethylene-7,8-dihydro-2-phenylquinazolin-5(6H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The methylbenzylamino and diphenylamino derivatives showed platelet antiaggregating activity in vitro superior to that of acetylsalicylic acid. The 1-pyrrolidinyl derivative showed appreciable local anesthetic activity in mice, whereas the whole series of compounds exhibited weak antiinflammatory activity in rats. more...

The synthesis of omega-dialkylaminoalkyl ethers 3 by the reaction of some 5-(arylmethylene)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6- hydroxyimines as sodium salts with the appropriate omega-chloroalkyldialkylamine in DMF solution is described. Some aminoethers 3 showed strong platelet antiaggregating activity in vitro superior to that of acetylsalicylic acid, as well as weak antiarrhythmic activity in rats and moderate infiltration anesthesia in mice. more...

The syntheses of 1-(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole 1 by reaction of 2-hydrazino-1-phenylethanol with dibenzoylmethane, of esters 2 and 2-dialkylaminoethyl ethers 3 starting from 1 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N,N-disubstituted 1-(2-amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles 5 by reaction of secondary amines with the tosylate of 1, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats. more...

The syntheses of 1-(2-hydroxy-3-phenoxypropyl)-3,5-diphenyl-1H-pyrazole 2 by reaction of 1-hydrazino-3-phenoxy-2-propranolol with dibenzoylmethane, of esters 3 and 2-dialkylaminoethyl ethers 4 starting from 2 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N-aryl carbamates 5 by reaction of 2 with aryl isocyanates, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats. more...

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-[1]benzothiepino [5,4-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzothiepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The 4-methylphenylamino derivative showed a local anesthetic activity in mice superior to that of lidocaine and the 4-morpholino derivative showed an antiarrhythmic activity in rats comparable to that of quinidine. more...

The synthesis of amides 3 and 4 starting from (1-phenyl-1H-indazol-4-yl)acetic and [(1-phenyl-1H-indazol-4-yl)oxy]acetic acids, respectively, as well as of 2-(1-phenyl-1H-indazol-4-yl)ethanamines 5 starting from 3, is described. Moreover, a number of 2-[(1-phenyl-1H-indazol-4-yl)oxy]ethanamines 7 and 3-[(1-phenyl-1H-indazol-4-yl)oxy]propanamines 8 were prepared starting from 1-phenyl-1H-indazol-4-ol. Some compounds 3, 4 and 7 showed an appreciable analgesic activity in mice, whereas compounds 4 were moderately active as antiinflammatory agents in rats. Some compounds 3, 4, 5, 7 and 8 showed also local anesthetic and a weak antipyretic activity in mice and rats, respectively. more...

The synthesis of some N,N-disubstituted 4-amino-3-phenyl-2H,5H-[1]benzothiopyrano [4,3-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-1-benzothiopyran-4-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid. more...

The synthesis of 1-acetyl-4-hydroxy-3,5-diphenyl-2-pyrazoline esters 3, 4-hydroxy-3,5-diphenyl-1H-pyrazole esters 5 and N-substituted 4-(3-amino-2-hydroxy-1-propoxy)-1-methyl-3,5-diphenyl-1H-pyrazoles 7, starting from 4-hydroxy-3,5-diphenyl-2-pyrazoline is described. Some of compounds 3, 5 and 7 showed a considerable antiarrhythmic and sedative activity in rats and mice, respectively, as well as a remarkable in vitro platelet antiaggregating activity. Moreover, the above compounds usually exhibited moderate antihypertensive, local anesthetic, analgesic and antiinflammatory activities in rats and mice. more...

The synthesis of 3-exo-dialkylamino-(Z)-camphoroximes 7 starting from a mixture of 3-endo- and 3-exo-bromocamphornitrimine, hydroxylamine hydrochloride and excess secondary amine (dimethylamine, pyrrolidine, piperidine or morpholine) is described. Compounds 7 gave a series of omega-dialkylaminoalkyl ethers 9, 10 and 11 by reaction of 7 as sodium salts with omega-chloroalkyldialkylamines in DMF solution. Some of compounds 9, 10, 11 showed an appreciable antiarrhythmic and local anesthetic activity in rats and mice, respectively. more...

Reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates 2 with phenylhydrazine gave the corresponding esters of 5-substituted 1-phenyl-1H-pyrazole-4-carboxylic acids 3 in high yields. Esters 3 were hydrolyzed to the relative carboxylic acids 4, which were converted by heating to 5-substituted 1-phenyl-1H-pyrazoles 5 in excellent yields. Reaction of methyl 5,5-dimethyl-3-dimethylaminomethylene-2,4-dioxohexanoate with phenylhydrazine afforded methyl 1-phenyl-4-pivaloyl-1H-pyrazole-5-carboxylate 8 b, which was converted as above to the corresponding carboxylic acid 10 b and this to 1-phenyl-4-pivaloyl-1H-pyrazole 11 b. Starting from 5-methoxymethyl-1-phenyl-1H-pyrazole, 1-phenyl-1H-pyrazole-5-acetic acid 18 and its alpha-methyl derivative 19 were also synthesized. Compounds 18, 19, 10 b and 11 b showed a strong antiinflammatory activity in rats; the same compounds in general as well as 8 b, showed appreciable analgesic and antipyretic activities in mice and rats, respectively. more...

The synthesis of N,N-disubstituted 3-(3,5-diphenyl-1H-pyrazol-1-yl)propanamides 2 a-d and 3-(3,5-diphenyl-1H-pyrazol-1-yl)propanamines 3 a-d starting from 3-(3,5-diphenyl-1H-pyrazol-1-yl)propanoic acid is described. Some of the above compounds showed considerable sedative and local anesthetic activities in mice, as well as a remarkable platelet antiaggregating activity in vitro. Moreover, the above compounds usually exhibited moderate analgesic and antiinflammatory activities in mice and rats, respectively. more...

The synthesis of 1,3,3-trimethyl-N-[(2-pyridyl)methyl]-2- oxabicyclo [2.2.2]octan-6-amine (II) (exo, endo mixture) starting from 1,3,3-trimethyl-N-nitro-2-oxabicyclo [2.2.2]octan-6-imine (I), as well as of a series of amides (III) derived from the above amine, is described. Some compounds (III) showed remarkable depressant and antiarrhythmic activities in rats and mice, respectively, whereas the clofibric acid amide (III e) showed an appreciable hypolipidemic activity in rats. Moreover, the above compounds usually exhibited a moderate infiltration anesthesia in mice, as well as a weak hypotensive and bradycardic activity in rats. more...

The synthesis of dialkylaminoalkyl ethers (III a-g) by reaction of 1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole (I) sodium salt with a series of omega-chloroalkyldialkylamines is described. Cyanoethylation of alcohol (I) and its 4-bromo derivative (II) gave 2-cyanoethyl ethers (III h, i), one of which (III h) was hydrolyzed to the corresponding carboxylic acid. Cyanoethylation of 3,5-diphenylpyrazole (IV) and its 4-bromo derivative (V) yielded nitriles (VI) and (VII), respectively, which were hydrolyzed to the corresponding carboxylic acids (VIII) and (IX). Some of the above compounds showed considerable hypotensive, depressant, antiarrhythmic and analgesic activities in mice and rats, as well as a remarkable platelet antiaggregating activity in vitro. Moreover, the above compounds usually exhibited a moderate antiinflammatory activity in rats and infiltration anesthesia in mice. more...