Synthesis and antiplatelet activity of some 2,7-di(N-cycloamino)-3-phenyl-1,8-naphthyridine derivatives.

Several 2,7-di(N-cycloamino)-3-phenyl-1,8-naphthyridine derivatives were synthesized and tested for their ability to inhibit human platelet aggregation in vitro induced by arachidonic acid, collagen and ADP. Only five compounds showed any appreciable activity, and the results of all the active derivatives were similar to those of papaverine in the test with arachidonic acid and collagen. Moreover, the most active compounds were investigated in the test with ADP and again showed a significant activity. The tested compounds that possessed the best activity were also shown to increase the c-AMP level significantly without involving the adenylyl cyclase system.

Synthesis and evaluation of antihypertensive activity of 1,8-naphthyridine derivatives. Part X.

A series of 4-(N-methylencycloalkylamino)-1,8-naphthyridine derivatives variously substituted in positions 2 and 7 were synthesized and pharmacologically investigated for possible antihypertensive activity. These compounds were tested to determine a possible vasodilator mechanism of action. Compounds 22, 23, 27-29, 47 and 48 showed satisfactory levels of potency (pIC(50)>5), which in one case (compound 23) reached a really interesting value (pIC(50) 6.92). Furthermore, for some selected compounds (19, 22, 23, 26, 28, 29, 47), the vasorelaxing activity was also evaluated in the presence of the guanylate cyclase blocker ODQ or of the adenylate cyclase blocker SQ 22536, and some of these can be considered as possible guanylate-cyclase inhibitors. Finally, compounds 19, 22 and 23 were also tested in the presence of the ATP-sensitive potassium channel blocker glybenclamide and seem to possess activating properties on these potassium channels.

Synthesis and beta-blocking activity of (R,S)-(E)-oximeethers of 2, 3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2, 3-b]pyridine:potential antihypertensive agents - part IX.

The synthesis of oximeethers of 2,3-dihydro-1,8-naphthyridine and 2, 3-dihydrothiopyrano[2,3-b]pyridine is described. These compounds exhibit a selective beta-blocking activity, with a selectivity towards beta(2)-receptors. Groups in the N(1) position giving rise to a considerable steric hindrance led to a higher beta(2)-blocking selectivity, whereas groups creating a moderate hindrance caused a weak but significant decrease in beta(2)-antagonist potency. Substitution of the N(1)-R group with a sulfur atom led to compounds possessing beta(1)-, beta(2)- and beta(3)-blocking properties. Compounds 9c(1) and 10a(1) showed a beta(3)-antagonist activity slightly lower than that of propranolol.

A novel class of highly potent and selective A1 adenosine antagonists: structure-affinity profile of a series of 1,8-naphthyridine derivatives.

A series of 1,8-naphthyridine derivatives (12-36), bearing a phenyl group in position 2 and various substituents in positions 4 and 7, were synthesized in an attempt to obtain potent, selective antagonists for the A1 adenosine receptor subtype. The compounds were tested to evaluate their affinity for A1 compared with A2A and A3 adenosine receptor subtypes. In binding studies in bovine brain cortical membranes, most of the compounds showed an affinity for A1 receptors in the low nanomolar range and two in the subnanomolar range with an interesting degree of A1 versus A2A and A3 selectivity. Comparison of the 4-substituted derivatives indicated that 4-OH substitution, with a 4-quinoid structure, causes an increase in the A1 and A2A affinity and generally also in A1 selectivity. The kind of substitution in position 7 can greatly modulate the affinity: the most interesting substituents in this position seemed to be electron-withdrawing groups; in particular the 7-chloronaphthyridine 25d showed a remarkable selectivity (A2A/A1 ratio of 670, A3/A1 ratio of 14,000) associated with a higher A1 affinity (Ki = 0.15 nM). NMR studies on these compounds 12-36 indicated that the 4-OH-substituted ones prefer the tautomer in which the oxygen in position 4 is in the quinoid form and the nitrogen in position 1 is protonated. Theoretical calculations are in agreement with the NMR data.

Synthesis and antiplatelet activity of some 3-phenyl-1,8-naphthyridine derivatives.

A series of 2-cycloalkylamino-3-phenyl-1,8-naphthyridine derivatives, variously substituted in the 6- and 7-positions were synthesized and tested for their ability to inhibit human platelet aggregation in vitro induced by arachidonate, collagen and ADP. Compounds 5a,b, 7a,b, 8a and 10c,d showed a remarkable activity similar to that of indomethacin in the test with arachidonate and collagen. In the test with ADP only compound 8a showed a significant activity. The presence of a morpholinyl or piperidinyl group in position 2 and of a chloro or methoxy group in position 7 of the 1,8-naphthyridine nucleus seem to favour a higher activity. However on the basis of the pharmacological results, no structure-activity relationship can be deduced. Compounds 5b and 7b, which possess the best activity in the arachidonate test, were also shown to increase the c-AMP level significantly, without involving the adenylyl cyclase system.

Synthesis and evaluation of antimycobacterial activity of 4-phenyl-1,8-naphthyridine derivatives.

Some 4-phenyl-1,8-naphthyridine derivatives with a piperazino group in the 2- and/or 7-position have been synthesized and evaluated for their tuberculostatic activity. The compounds 1, 6, 10, 17b,c and 19i showed a marked activity against Mycobacterium tuberculosis H37Rv. For this series of compounds, submitted to biological screening, no structure-activity relationship can be deduced.

Synthesis of some 4H-pyrido[1,2-a]pyrimidin-4-ones investigated as antimicrobial agents.

Synthesis of some 4H-pyrido[1,2-a]pyrimidin-4-ones and assay of their antibacterial and antifungal activity are reported. Compounds 3a-e,g were prepared by reaction of substituted 2-chloromethyl-4H-pyrido[1,2-a]pyrimidin-4-ones 2a-c with suitable amines. These compounds and the previously obtained analogues 5a-o and 6a,b have been tested for their antimicrobial activity. All tested compounds were devoid of antimicrobial activity.

Synthesis and local anesthetic activity of (E)- and (Z)-diethylaminoethyliminothers of 1,8-naphtyridine.

A series of (E)- and (Z)-diethylaminoethylimino ethers of 1.8-naphthyridine was prepared and characterized. Preliminary studies showed that none of the tested compounds presented noteworthy local anesthetic activity.

Synthesis of pyrido[1,2-a]pyrimidin-4-ones. Potential antihypertensive agents. III.

Several 4H-pyrido[1,2-a]pyrimidine derivatives with a basic substituent in the 2-position have been synthesized. All the compounds tested showed no appreciable antihypertensive activity.

Synthesis of 1,8-naphthyridine derivatives. Potential antihypertensive agents. II.

Several 1,8-naphthyridine derivatives have been synthesized and pharmacologically investigated. Some of them exhibited a marked antihypertensive activity on spontaneously hypertensive rats.

Synthesis of new 6H-indolo[2,3-b] [1,8]naphthyridines and their specific inhibition of benzodiazepine receptor.

Some 3-amino- and 3-hydroxy-8-halosubstituted 6H-indolo[2,3-b] [1,8]naphthyridines were synthesized and tested for their affinity for the benzodiazepine receptor in bovine cortical membranes. All prepared compounds were more active than the corresponding 8-unsubstituted derivatives. Moreover, among these compounds the 8-chloroindolonaphthyridines were clearly the most potent.

Synthesis and pharmacological activity of some 9-aryl-8-azapurine derivatives.

Because of the biological interest of 8-azaanologous of purine bases, the preparation of some 8-azapurines (IV) and (V), substituted in 9 position with aryl groups, is described. Compounds were obtained by closure of a pyrimidine nucleus on performed 5-amino-1,2,3-triazole derivatives. Some substances, subjected to pharmacological screening, showed an interesting antiallergic activity.

Synthesis and pharmacological activity of three new 9-aryl-8-azaadenine derivatives.

This paper describes the synthesis of three new 9-aryl-8-azaadenine derivatives (Ic, d, e) and of some related compounds, using the appropriate 1-substituted-5-amino triazoles (IV) as starting material. The new azaadenines were subjected to pharmacological screening and the carboxylic compound (I c) showed an interesting antiallergic activity, depending on the presence of the free acid function.

[1,2,3-triazole derivatives of arylalkanoic acids]. / Derivati 1,2,3-triazolici di acidi arilalcanoici.

A series of several 1,2,3-triazole derivatives, by reaction of p-azidophenylacetic and 2-(p-azidophenyl)propionic acids with active methylene compounds, was synthesized. Some of the derivatives obtained were subjected to pharmacological study and among these compounds (II m) showed an analgesic activity 2.5 times greater than phenylbutazone.

[Synthesis and pharmacological activity of 1,2,3-triazole derivatives of naphthalene, quinoline and pyridine]. / Sintesi ed esame farmacologico di derivati 1,2,3-triazolici della naftalina, chinolina e piridina.

The preparation of three series of 1,2,3-triazol derivatives, with a naphthalene, quinoline or pyridine ring in 1 position, is described. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.

Synthesis of some 11H-indolo[3,2-c][1,8]naphthyridines.

The preparation of some 11H-indolo[3,2-c] [1,8]naphthyridines (V), having oxygen functions at positions 3 or 3 and 10 or 3 and 8, as in steroidal active compounds, is described. Compounds (V) were obtained using the Fisher indole synthesis. The preparation of the parent nucleus: 11H-indolo [3,2-c] [1,8]naphthyridines (V n) is also described. Some compounds were subjected to pharmacological screening, but none was found to be significantly active.

[1.3-Dipolar cycloaddition products of 8-azidotetrazol[1,5a][1,8]naphthyridines with alkynes]. / Cicloaddizione 1,3-dipolare dell'8-azidotetrazolo[1,5-a][1,8]naftiridina ad alchini.

A series of new 1,2,3-triazol derivatives, obtained by reaction of 8-azidotetrazol[1,5-a][1,8]naphthyridine with alkynes, is described. Some of the tested compounds showed activity against hypoxia in mice.

[Synthesis and biological activity of 1,2,3-triazol-1,8-naphthyridines]. / Sintesi e attivita biologica di derivati 1,2,3-triazol-1,8-naftiridinici

The reaction of 2-methyl-5-azido-1,8-naphthyridine with active methylene compounds was investigated. Several naphthyridines which possess the 1,2,3-triazole ring as a substituent were obtained. Among these compounds (IV o) showed an analgesic activity twice that of phenylbutazone.

[Preparation of some pyrido (2,3-e)-1,4-diazepines]. / Preparazione di alcune pirido (2,3-e)-1,4-diazepine

By treating pyrido (2,3-e)-1,4-diazepinones with alkyl halides, N4-alkylpyrido (2,3-e)-1,4-diazepines were obtained. In addition a number of N1-alkylpyrido (2,3-e)-1,4-diazepines were prepared from alkyltetrahydronaphthyridinones by the Schmidt reaction. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.