Recordati S.a. Chemical and Pharmaceutical Company

Recordati S.a.

Dante Nardi

Gabriele Graziani

Amedeo Leonardi

Pietro Cazzulani

Gianni Motta

Alberto Tajana

Giorgio Bianchi

Rodolfo Testa

Silvano Casadio

Alberto Catto

Elena Massarani

Renzo Pennini

Ludwig Degen

Maria J Magistretti

Amedeo Leonardo

Gabriel Kraziani

Mario Veronese

Alberto Tajano

Novel antihypertensive and coronary dilating asymmetric diesters of 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid (or the stereoisomers or pharmaceutically acceptable acid addition salts thereof) have the general formula (I): ##STR1## wherein Ph is phenyl, Ar is 2-nitrophenyl, 3-nitrophenyl, 2,3-dichlorophenyl or benzofurazan-4-yl, A is a straight or branched chain alkylene radical having from 2 to 6 carbon atoms, R is a straight or branched chain alkyl radical having from 1 to 6 carbon atoms, optionally mono-substituted by an alkoxy substituent having from 1 to 6 carbon atoms, R.sub.1 is hydrogen, hydroxy or an alkyl radical having from 1 to 4 carbon atoms, and R.sub.2 is hydrogen or methyl. The subject diesters are facilely prepared from the aldehydes ArCHO and esters of acetoacetic and 3-aminocrotonic acids.

Novel asymmetric diesters of

N-piperazinylalkanoylanilides of the formula ##STR1## wherein n is 0, 1 or 2, each of R and R.sub.1 is H or alkyl, and each of R.sub.2, R.sub.3 and R.sub.4 is H, halogen, alkyl, hydroxyalkyl, alkoxy, aralkoxy, alkylthio, aralkylthio, alkylsulphonyl, alkylsulphenyl, NO.sub.2, NH.sub.2, alkylamino, acylamino, ureido, alkylureido, alkylsulphonylamino, CF.sub.3, acyl, CN, COOH, alkoxycarbonyl, NH.sub.2 CO, SO.sub.3 H, guanidinosulphonyl, carbamoyloxy, OH, acyloxy, alkylsulphonyloxy, alkylenedioxy or SO.sub.2 NR.sub.5 R.sub.6 wherein each of R.sub.5 and R.sub.6 is H, alkyl, aryl or acyl and their pharmaceutically acceptable acid addition salts, are antihypertensive agents.

Antihypertensive N-piperazinylalkanoylanilides

The novel flavonyl-1,4-dihydropyridines having the general formula (I): ##STR1## are therapeutically effective calcium antagonists and smooth muscle relaxant.

Therapeutically active flavonyl-1,4-dihydrophyridines

Antihypertensive diphenylpropyl aminopropyl ester of

Novel antihypertensive and coronary dilating asymmetric diesters of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid (or the stereoisomers or pharmaceutically acceptable acid addition salts thereof) have the general formula (I): ##STR1## wherein Ph is phenyl, Ar is 2-nitrophenyl, 3-nitrophenyl, 2,3-dichlorophenyl or benzofurazan-4-yl, A is a straight or branched chain alkylene radical having from 2 to 6 carbon atoms, R is a straight or branched chain alkyl radical having from 1 to 6 carbon atoms, optionally mono-substituted by an alkoxy substituent having from 1 to 6 carbon atoms, R.sub.1 is hydrogen, hydroxy or an alkyl radical having from 1 to 4 carbon atoms, and R.sub.2 is hydrogen or methyl. The subject diesters are facilely prepared from the aldehydes ArCHO and esters of acetoacetic and 3-aminocrotonic acids.

N-(3,3-diphenylpropyl) aminoethyl esters of

Novel piperazine derivatives having the general formula: ##STR1## wherein R is hydrogen or lower alkyl, A is straight or branched chain lower alkyl, and R.sub.1 and R.sub.2 are each hydrogen, amino, alkylamino, dialkylamino, mono- or di(hydroxyalkyl)amino, morpholino, pyrrolidino, piperidino, N-alkylpiperazino, 1,3-dithiolan-2-ylidenamino, or N-alkylureido, with the proviso that at least one of R.sub.1 and R.sub.2 is other than hydrogen, or the isomeric mixtures, individual enantiomers or pharmaceutically acceptable acid addition salts thereof, are therapeutically useful antianaphylactic and antibronchospastic agents.

Antianaphylactic and antibronchospastic piperazinyl-(N-substituted

##STR1## Esters I (Ar=3-nitrophenyl or 2,3-dichlorophenyl, A=C.sub.2 -C.sub.6 alkylene, R=C.sub.1 -C.sub.6 alkyl optionally C.sub.1 -C.sub.6 alkoxy monosubstituted, R.sub.1 =C.sub.1 -C.sub.4 alkyl) have antihypertensive activity and are effective against coronary heart diseases. They are prepared starting from the aldehyde ArCHO and esters of acetoacetic acid and 3-aminocrotonic acid. Pharmaceutical preparations containing them are also described.

Antihypertensive esters of 1,4-dihydro-2,6-dimethyl-3-(alkoxycarbonyl or

Novel 3-methylflavone-8-carboxylates having the structural formula (I): ##STR1## wherein Z is N-methylpiperidinyl, tropinyl or quinuclidinyl, or a group having the structural formula (II): ##STR2## in which n is 0 or 1, R is hydrogen or alkyl having from 1 to 4 carbon atoms, or phenyl, R.sub.1 is hydrogen or alkyl having from 1 to 4 carbon atoms, R.sub.2 is hydrogen or hydroxy, and further wherein R, R.sub.1 and R.sub.2 may together form, with the carbon atoms from which they depend, a cycloalkyl ring having from 4 to 6 carbon atoms, and R.sub.3 is hydrogen or alkyl having from 1 to 4 carbon atoms, with the proviso that R, R.sub.1, R.sub.2 and R.sub.3 cannot at the same time all be hydrogen, and the pharmaceutically acceptable salts thereof, are effective smooth muscle relaxants, calcium blockers, anaesthetics and anti-inflammatories.

Certain piperidino-lower-alkylene esters of

The .omega.-[4-(2-pyridyl)-piperazino]-alkanoylanilide compounds having the structural formula (I): ##STR1## wherein n is 1, 2 or 3, each of R, R.sub.1, R.sub.2 R.sub.3, and R.sub.4 is independently hydrogen, halogen, alkyl, alkoxy, OH, NH.sub.2, CF.sub.3, CN, alkylthio, 1-hydroxyalkyl, alkanoyl, NH.sub.2 CO, NH.sub.2 SO.sub.2, alkoxycarbonyl, alkylsulfonyl, benzyloxy, alkanoylamino, NH.sub.2 CONH, 3-phenylureido, 3-alkylureido or alkoxyoxalylamino, R.sub.5 is hydrogen or alkyl, and R.sub.6 is hydrogen or alkoxy, and the pharmaceutically acceptable salts thereof, are effective antianaphylactics, antibronchospastics, antihistaminics, sedatives, analgesics, antiserotonics and blood-pressure-lowering agents.

Therapeutically effective

The novel anthranilic acid derivatives having the structural formula (I): ##STR1## wherein n is 0, 1 or 2, one of R.sub.1 and R.sub.2 is chloro or trifluoromethyl and the other is hydrogen, and R is 2-oxo-3-oxolanyl or 2-oxo-3-oxazolidinyl, are effective analgesics and anti-inflammatories.

Analgesically or anti-inflammatory effective 4-quinolyl anthranilic acid

The N-substituted-4-(optionally substituted)-2-, 3- or 4-piperidyl N-(7- or 8-substituted-4-quinolyl)-anthraniloyloxyalkanoates having the structural formula (I): ##STR1## in which R is a straight or branched chain alkyl radical having from 1 to 4 carbon atoms; an alkenyl or alkynyl radical having from 2 to 6 carbon atoms; a benzyl, phenethyl, 4-nitrophenethyl or 4-aminophenethyl radical; or a phenacyl, benzoylethyl, .beta.-hydroxyphenethyl or .alpha.-hydroxyphenylpropyl radical, optionally substituted on the phenyl ring by one or more halogen atom, trifluoromethyl, nitro or amino substituents, or an alkyl substituent having from 1 to 4 carbon atoms or an alkoxy substituent having from 1 to 4 carbon atoms; R.sub.1 is a hydrogen atom or a phenyl radical; each of R.sub.2 and R.sub.3 is independently a hydrogen atom or an alkyl radical having from 1 to 4 carbon atoms; one of R.sub.4 and R.sub.5 is a chlorine atom or a trifluoromethyl radical and the other of R.sub.4 and R.sub.5 is a hydrogen atom; and the pharmaceutically acceptable salts of such esters; are effective analgesics, anti-inflammatories and antidepressants; are also strong inhibitors of platelet aggregation, and thus too are useful in the treatment of cerebral thrombosis, cerebral and cardiac infarction, and arteriosclerotic disorders.

Therapeutically effective piperidyl

Novel cystine derivatives having the structural formula (I): ##STR1## wherein R is benzyloxycarbonyl or tosyl, and the pharmaceutically acceptable acid addition salts thereof, are effective expectorants and antitussives, and are also effective for the liquescence of respiratory tract fluids.

Therapeutically effective derivatives of cystine

Imidazole derivatives of the formula I and pharmaceutically acceptable acid addition salts thereof are provided: ##STR1## In the formula, R.sub.4 1- or 2-naphthyl, optionally substituted with Cl, Br, or I; 1,2,3,4-tetrahydro-6-naphthyl; 3-duryl, optionally 6-substituted by Cl, Br, I, NO.sub.2, CH.sub.3 or benzyl; mesityl, phenyl 2-, 3- or 4-substituted by OH, NH.sub.2, NO.sub.2, CH.sub.3 CONH, phenyl, phenoxy, cyclohexyl, phenylthio, benzylthio, C.sub.1 -C.sub.6 alkyl or C.sub.1 C.sub.6 alkylthio; 4-bibenzylyl; 3,4-dihydroxyphenyl,

Imidazole derivatives

There are provided 2,4-dichloro-4'-phenyl-.alpha.-(N-imidazolyl-methyl)-dibenzyl ether, 2,4-dichloro-4'-phenylthio-.alpha.-(N-imidazolyl-methyl)-dibenzyl ether and pharmaceutically acceptable acid addition salts thereof. These compounds show activity against some fungi, yeasts and gram positive aerobic and anaerobic bacteria. The new compounds can be prepared by condensing 1-(2',4'-dichlorophenyl)-2-(N-imidazolyl)-ethanol with 4-chloromethyl-biphenyl, 4-bromomethyl-biphenyl, 1-phenylthio-4-chloromethyl-benzene or 1-phenylthio-4-bromomethyl-benzene in a solvent, most preferably dimethylsulphoxide.

Substituted dibenzyl ethers and pharmaceutical compositions containing

Novel derivatives of 3H-1,5-benzodiazepine and of their salts of addition with acids, including their quaternary ammonium salts, having the general formula: ##EQU1## are provided. Such compounds are effective therapeutically against a large spectrum of gram positive bacteria and APR8 influenza virus. The invention also provides a novel method of preparing compounds having the formula: ##EQU2## wherein R and R' are the same as above, by reacting orthophenylenediamine with a benzoyldithioacetic acid having the formula: ##EQU3## wherein R and R' are as defined above.

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Milan, Italy

Dante Nardi