RU2000131690A

RU2000131690A - NITRATE SALTS OF HYPOTENSIC MEDICINES

Info

Publication number: RU2000131690A
Application number: RU2000131690/04A
Authority: RU
Inventors: Солдато Пьеро Дел
Original assignee: Никокс С.А.
Priority date: 1998-06-19
Filing date: 1999-06-15
Publication date: 2002-11-10

Claims

1. Nitrate salts of compounds selected from the following classes:
Class (Alb):

R _A1 = -CH ₂ OH,

R ¹ = H, Cl;
R _A1 ^II = (CH ₂ ) ₃ -CH ₃ , -O-CH ₂ -CH ₃ ;
R _A1 ^III = H, free valence;
R _A1 ^IV = free valence;
or R _A1 = -O and R _A1 ^III = free valence form with a carbon atom in the 5 position keto group,
or R _A1 ^IV , R _A1 ^III , R _A1 ^I and carbon atoms in the 4 and 5 positions of the heterocyclic ring of formula (A1b) form an aromatic ring containing a COOH group (ICC),

or R _A1 ^I , R _A1 ^IV and a carbon atom in the 4 position of the heterocyclic ring of the formula (Alb) form the following saturated ring having five carbon atoms:

when R _A1 ^III = free valence and R _A1 ^IV = free valence is a double bond between carbon atoms in 4 and 5 positions of the heterocyclic ring of formula (Alb),
Class (Alc):

The predecessor of the class (Alc) is known as valsartan;
Class (A2):
1 (2H) -phthalazine nongidrazone (hydralazine); 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide (minoxidil); 1 - [[3- (4,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazole [4,3-d] pyrimidin-5-yl) -4-ethoxyphenyl] sulfonyl] -4 -methyl piperazine (sildenafil), 2- (2-propyloxyphenyl) -8-azapurin-6-one (zaprinast);
Class (A3):

R _B1 ^VI = H
R _B1 ^VII = H
R _B1 ^I and R _B1 ^II are equal or different from each other and mean H, CH ₃ ,
R _B1 ^III = H, CH ₃ ,

-CH ₂ -CH ₂ -Y _B1 (XIe),
in the formula (XId) t = 0.1;
in the formula (Xle) Y _B1 can have the following meanings:

in the formula (XIf), Z = H, -OCH ₃ ;
in the formula (A3):
X _B1 = -O-, -S-;
n and m are equal or different from each other and are 0, 1;

—CH ₂ —CH (OH) —CH ₂ —NH — CH (CH ₃ ) ₂ (XIr),

in the formula (XIr):
S ₁ = H, CN, OCH ₃ , CH ₃ , —CH ₂ —CH ₃ , —O — CH ₂ —COHH — CH ₃ , —COCH ₃ , —CO— (CH ₂ ) ₂ —CH ₃ , —O- CH ₂ -CH = CH ₂ , -CH ₂ -CH = CH ₂ , cyclopentyl or

S ₂ = H, CH ₃ , Cl, -SOCH ₃ , -CONH ₂ ;
S ₃ = H, F, Cl, OH, NO ₂ , —CH ₂ —CO — NH ₂ , - (CH ₂ ) ₂ —OCH ₃ , —NH-COCH ₃ ,
—CH ₂ —O — CH ₂ —CH ₂ —O — CH (CH ₃ ) ₂ , —CH ₂ —CH ₂ —COOCH ₃ , —NH — CO — N (C ₂ H ₅ ) ₂ ,
-NH-CO- (CH ₂ ) ₂ -CH ₃ , -NH-SO ₂ -CH ₃ , -NH-CO-NH- [cyclohexyl], -CH ₂ -CH ₂ -O-CH ₂ - [cyclopropyl]; S ₄ = H, Cl, —CH ₂ —CH ₂ - or
S ₁ , S ₂ and carbon atoms in 2 and 3 positions of the aromatic ring of six carbon atoms of the above-mentioned radical (XIp) form the following ring:

where ^{(*) is} an atom located near the aromatic ring of formula XIp ^VII
B = -CH ₂ -, -NH-, -CH-CH-, ^(*) -CO-CH ₂ -;
A = —O—, ^(*) —CH ₂ —CH (OH) -, ^(*) —O — CH ₂ -, ^(*) —S — CH ₂ -, —CH ₂ —CH ₂ , —CH ₂ - ,
W ₁ = H, free valence;
W ₂ = free valence, H, OH, -CH ₃ , -ONO ₂ , -O;
or A is a tertiary carbon atom and at the same time W ₁ means the free valence to form a double bond -CH = CH- between A and the carbon atom in the 1 'position;
or W ₁ , W ₂ a carbon atom in the 1 ′ position and A form an aromatic ring having six carbon atoms according to the following formula:

when W ₂ = -O and W ₁ = free valence with a carbon atom in the 1 ′ position of the radical (XIp ^VII ) a ketone group is formed;
or when in formula (XIp) S ₄ = -CH ₂ -CH ₂ -, and in formula (A3) X _B1 is oxygen, m = n = 1 and R _B1 ^VII = free valence, the next ring with carbon atoms in 1 is formed and 6 position of the aromatic ring of the radical (XIp):

or when in formula (A3) n = m = 1, both R _B1 ^VII and R _B1 ^VI = free valence, S ₄ and carbon atoms in 1 and 6 position of the aromatic ring of formula (XIp), S ₁ is -CH ₂ -CH ₃ , together with the carbon atom - | C | _n - and X _B1 = oxygen of formula (A3) form the following ring:

and, in addition, the following compounds:
2-hydroxy-5- [1-hydroxy-2 - [(1-methyl-3-phenylpropyl) amino] ethyl] benzamide (labetalol), 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) - 4 - [(tetrahydro-2-furanyl) carbonyl] piperazine (terazosin), 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4- (2-furanylcarbonyl) piperazine (prazosin);
excluding in formula (A3) the compounds obtained when the substituents of the specified formula have the following meanings:
R _B1 ^I = R _B1 ^II = R _B1 ^III = CH ₃ ; R _B1 ^V = H; n = 1; m = 1
R _B1 ^VI = R _B1 ^VII = H, X _B1 = 0; R _B1 ^IV = radical XI _p , where
S ₁ = S ₂ = S ₄ = H, S ₃ = -NH-CO-NH- [cyclohexyl] (talinol);
R _B1 ^I = R _B1 ^II = CH ₃ ; n = 1; R _B1 ^III = R _B1 ^V = R _B1 ^VII = R _B1 ^VII = H;
X _B1 ^VI = 0; R _B1 ^IV is an aromatic ring (XI _p )
with S ₂ = S ₃ = S ₄ = H, S ₁ = -CH ₂ -CH-CH ₂ (alprenolol)
Class (A4):
(A4a) β - [(2-methylpropoxy) methyl] -N-phenyl-N- (phenylmethyl) -1-pyrrolidine ethanamine (bepridyl), (2S-cis) -3- (acetyloxy) -8-chloro-5- [ 2- (dimethylamino) ethyl] -2,3-dihydro-2- (4-methoxyphenyl) -1,5-benzothiazepin-4 (5H) -one (Clentiazem), (2S-cis) -3- (acetyloxy) - 5- [2- (dimethylamino) ethyl] -2,3-dihydro-2- (4-methoxyphenyl) -1,5-benzothiazepin-4 (5H) -one (diltiazem), γ-phenyl-N- (1- phenylethyl) benzene-propanamine (fendilin), α- [3 - [[2- (3,4-dimethoxyphenyl) ethyl] methylamine] propyl] -3,4,5-trimethoxy-α- (1-methylethyl) -benzeneacetonitrile ( gallopamyl), (1S-cis) methoxyacetic acid-2- [2 [[3- (1H-benzimidazol-2-yl) propyl] methylamino] ethyl] -6-f torus-1,2,3,4-tetrahydro-1- (1-methylethyl) -2-naphthalene ester (mibefradyl), N- (1-methyl-2-phenylethyl) -γ-phenylbenzenepropanamine (prenyl amine), (R) -2- [2- [3 - [[2- (1,3-benzodioxol-5-yloxy) ethyl] methylamino] propoxy] -5-methoxyphenyl] -4-methyl-2H-1,4-benzothiazin-3 ( 4H) -one (semothiadyl), N- (1,1-dimethylethyl) -α-methyl-γ-phenylbenzenepropane-amine (terodilin), α- [3 - [[2- (3,4-dimethoxyphenyl) -ethyl] methyl amino] propyl] -3,4-dimethoxy-α- (1-methylethyl) -benzeneacetonitrile (verapamil);
(A4b) 3-ethyl-5-methyl ester 2 - [(2-aminoethoxy) methyl] -4- (2-chlorophenyl) -1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid (amlodipine), 1,4-dihydro-2,6-dimethyl-4- (2-nitrophenyl) -3,5-pyridinedicarboxylic acid methyl aryl-2-oxopropyl ester (aranidipine), methyl 1- (phenylmethyl) -3-pyrrolidinyl ether [S - (R *, R *)] -1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid (barnidipine), methyl-1- (phenylmethyl) -3- (R *, R *) - ± -1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid piperidinyl ester (benidipine), 2-methoxyethyl-3-phenyl 2-Propenyl ester (E) - ± -1,4-dihydr -2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid (cilidipine), 2 [phenyl (phenylmethyl) amino] 5- (5,5-dimethyl-1,3,2-ethyl ester) dioxaphosphorinan-2-yl) -1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3-pyridine carboxylic acid P-oxide (etonidipine), 2 [[[4-fluorophenyl) methyl] methylamino] ethyl-1-methyl ethyl ester ± -4- (1, 3-benzodioxol-4-yl) -1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid (elgodipin), ethyl methyl ester 4- (2 , 3-dichlorophenyl) -1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid (felodipine), 5-methyl-3- (1-methyl) -ethyl ester 4- (4-benzofurazanyl) - 1,4-dihydro-2,6-d methyl-3,5-pyridinedicarboxylic acid (isradipine), (E) -4- [2- [3- (1,1-dimethylethoxy) -3-oxo-1-propenyl] phenyl] -1,4-dihydro diethyl ether -2,6-dimethyl-3,5-pyridinedicarboxylic acid (lacidipine), 2 - [(3,3-diphenylpropyl) methylamine] -1,1-dimethyl ethyl methyl 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid (lercanidipine), 2- [4- (diphenylmethyl) -1-piperazinyl] ethyl 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) ) -3,5-pyridinedicarboxylic acid (manipipine), methyl-2- [methyl (phenylmethyl) -amino] ethyl ester 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5- pyridi dicarboxylic acid (nicardipine), 1, 4-dihydro-2,6-dimethyl-4- (2-nitrophenyl) -3,5-pyridinedicarboxylic acid dimethyl ester (nifedipine), 3-methyl-5- (1-methylethyl) ether 2-cyano-1,4-dihydro-6-methyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid (nilvadipine), 2-methoxyethyl-1-methyl ethyl ester 1,4-dihydro-2,6- dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid (nimodipine), 1,4-dihydro-2,6-dimethyl-4- (2-nitrophenyl) -3,5- methyl methyl-2-methylpropyl ether pyridine dicarboxylic acid (nizoldipine), 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic ethyl methyl ester acids (nitrendipine);
(A4c) 1- (diphenylmethyl) -4- (3-phenyl-2-propenyl) piperazine (cinnarizine), (E) -1- [bis (4-fluorophenyl) methyl] -4- (3-phenyl-2- propenyl) piperazine (flunarizin), 4- [4,4-bis (4-fluorophenyl) butyl] -N- (2,6-dimethylphenyl) -1-piperazine acetamide (lidoflazin), 1- [bis (4-fluorophenyl) methyl ] -4 - [(2,3,4-trimethoxyphenyl) methyl] piperazine (lomerizine);
(A4d) N, N-dimethyl-3 - [[1- (phenylmethyl) -cycloheptyl] oxy] -1-propanamine (benciclan), 1- [2- [2- (diethylamino) ethoxy] phenyl] -3-phenyl -1-propanone (etaphenone), 3,4-dimethoxy-N-methyl-N- [3- [4 - [[2- (1-methylethyl) -1-indolizinyl] sulfonyl] phenoxy] propyl] benzene ethanamine (phantofaron );
Class (A7):
(A7a) 6-chloro-3,4-dihydro-3 - [(2-propenylthio) methyl] -2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (althiazide), 3,4- dihydro-3- (phenylmethyl) -6- (trifluoromethyl) -2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (bendroflumethiazide), (6-chloro-3 - [[(phenylmethyl) thio] methyl] -2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide (benzthiazide), 6-chloro-3,4-dihydro-3- (phenylmethyl) -2H-1,2,4- Benzothiadiazine-7-sulfonamide 1,1-dioxide (benzylhydrochlorothiazide), 6-chloro-3,4-dihydro-3- (2-methylpropyl) -2H-1,2,4-benzothiadiazin-7-sulfonamide 1,1 -dioxide (butiazid), 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (chlortia id), 2-chloro-5- (2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl) benzobesulfonamide (chlorthalidone), 6-chloro-3- (cyclopentylmethyl) -3,4 -dihydro-2H-1,2,4-benzothiadiazin-7-sulfonamide 1,1-dioxide (cyclopentyazide), 3-bicyclo [2.2.1] -hept-5-ene-2-yl-6-chloro 3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (cyclothiazide), 6-chloro-3,4-dihydro-3 - [[(2,2,2-trifluoroethyl ) thio] methyl] -2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (epithiazide), 6-chloro-3-ethyl-3,4-dihydro-2H-1,2,4- Benzothiadiazine-7-sulfonamide 1,1-dioxide (ethiazide), 7-chloro-1,2,3,4-tetrahydro-4-oxo-2-phenyl-6-quinazoline sulfonamide (fenhizone), 3- (am Osulfonyl) -4-chloro-N- (2,3-dihydro-2-methyl-1H-indole-1-yl) benzamide (indapamide), 6-chloro-3,4-dihydro-2H-1,2,4 -benzothiadiazine-7-sulfonamide 1,1-dioxide (hydrochlorothiazide), 3,4-dihydro-6- (trifluoromethyl) -2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (hydroflumethiazide), 6 -chloro-3- (chloromethyl) -3,4-dihydro-2-methyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (methiclothiazide), 3,4-dihydro-6-methyl -2H-1-benzothiopyran-7-sulfonamide 1,1-dioxide (methicrane), 7-chloro-1,2,3,4-tetrahydro-2-methyl-3- (2-methylphenyl) -4-oxo-6 -quinazolin sulfonamide (metolazone), 6-chloro-3 - [(4-fluorophenyl) -methyl] -3,4-dihydro-2H-1,2,4-benzot adiazin-7-sulfonamide 1,1-dioxide (paraflutizide), 6-chloro-3,4-dihydro-2-methyl-3 - [[(2,2,2-trifluoroethyl) thio] methyl] -2N-1, 2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (polythiazide), 7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-6-quinazoline sulfonamide (quintazone), 6-chloro -3,4-dihydro-3-trichloromethyl-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (texloziaz), 6-chloro-3- (dichloromethyl) -3,4-dihydro-2H -1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (trichloromethiazide);
(A7b) 3,7-dihydro-1,3-dimethyl-7- (4-morpholinylmethyl) -1H-purin-2,6-dione (7-morpholinomethyltheophylline), 3,7-dihydro-1- (2-hydroxypropyl -3,7-dimethyl-1H-purine-2,6-dione (proteobromin), 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione (theobromine);
(A7c) 6-amino-3-ethyl-1- (2-propenyl) -2,4- (1H, 3H) -pyrimidinedione (aminometradin), 6-amino-3-methyl-1- (2-methyl-2 -propenyl) -2,4- (1H, 3H) -pyrimidinedione (amisometradine);
(A7d) N-phenyl-1,3,5-triazin-2,4-diamine (amanosin), 3,5-diamino-N- (aminoiminomethyl) -6-chloropyrazinecarboxamide (amiloride), N- (4-chlorophenyl) -1,3,5-triazin-2,4-diamine (chlorazanil), [3-methyl-4-oxo-5- (1-piperidinyl) -2-thiazolidinylidene] acetic acid ethyl ester (etozoline), 6-hydrazino -3-pyridazinecarboxamide (hydracarbazine), 5-amino-2 [1- (3,4-dichlorophenyl) ethyl] -2,4-dihydro-3H-pyrazol-3-one (muzolimine), 2- (2,2- dicyclohexylethyl) piperidine (perhexeline), 3- (aminosulfonyl) -5- (butylamino) -4-phenoxybenzoic acid (bumetanide), 5- (aminosulfonyl) -4-chloro-2 - [(2-furanylmethyl) -amino] benzoic acid ota (Furosemide), N - [[(1-methylethyl) amino] carbonyl] -4 - [(3-methylphenyl) amino] -3-pyridinesulfonamide (Torasemide).

2. Nitrate salts according to claim 1 of the following compounds of class (Alb) when X _AI = (IXa), R _AI = CH ₂ OH, R _AI ^I = Cl, R _AI ^III = R _AI ^IV = free valencies, forming a double bond - CH = CH- with carbon atoms in 4 and 5 positions of the heterocyclic ring of the formula (Alb), R _AI ^II = - (CH ₂ ) ₃ - CH ₃ is the residue of losartan; as in losartan, but with R _AI = -O and R _AI ^III - free valence, resulting in a combination of a ketone group, R _AI ^I and R _AI ^IV with a carbon atom in combination with a carbon atom in the 5 position of the heterocyclic ring of formula (Alb) in the 4 position of the heterocyclic ring form a saturated ring having 5 carbon atoms (IXd), it is a residue of irbesartan, as in losartan, but with R _AI ^II = -O-CH ₂ -CH ₃ , R _AI together with R _AI ^I and carbon atoms in the 4 and 5 positions of the heterocyclic ring with R _AI ^IV and R _AI ^III - free valencies form an aromatic radical containing -COO H group (IXC) is the residue of candesartan; as in losartan, but with X _AI = -COOH, R _AI = (IXb), R _AI ^I = H, R _AI ^IV and R _AI ^III are free valences that form a double bond between the carbon atoms in the 4 and 5 positions of the heterocyclic ring of the formula (A1b) is the residue of eprosartan.

3. Nitrate salts according to claim 1 of the following compounds of class (A3): when R _BI ^I = H, R _BI ^II and R _BI ^III = CH ₃ , R _BI ^V = H, R _BI ^VI = R _BI ^VII = H, m = n = l, X _BI = -O-, R _BI ^IV = (XIp), where S ₁ = S ₂ = S ₄ = H, S ₃ = -CH ₂ -CO-NH ₂ , this is the residue of atenolol, as in atenolol, but with R _BI ^IV = (XIs), it is a residue of befunolol; as in atenolol, but with S ₁ = COCH ₃ , S ₃ = -NH-CO- (CH ₂ ) ₂ -CH ₃ , S ₂ = S ₄ = H, this is an acebutalol residue, as in atenolol, but with S ₃ = -CH ₂ -CH ₂ -O-CH ₂ - (cyclopropyl), this is the residue of betaxolol; as in atenolol, but with S ₃ = -CH ₂ -O-CH ₂ -CH ₂ -O-CH (CH ₃ ) ₂ , this is a residue of bisoprolol, as in atenolol, but with S ₁ = (XIp ^II ) S ₃ = H and R _BI ^I = CH ₃ , this is the residue of butetolol, as in atenolol, but with R _BI ^IV (XIp ^VIII ), where B = -NH-, this is the residue of carazolol, as in atenolol, but with S ₃ = -CH ₂ —CH ₂ —COOCH ₃ , this is an esmolol residue, as in atenolol, but with R _BI ^IV = (XIu), this is an indenolol residue, as in atenolol, but with S ₃ = - (CH ₂ ) ₂ —OCH ₃ , this is the residue metoprolol, as in atenolol, but with S ₃ = NO ₂ , is a residue of nifenalol, as in atenolol, but with S ₁ = -O-CH ₂ -CH = CH ₂ and S ₃ = H is a residue of oxprenolol, as in atenolol, but with S ₃ = -NH-COCH ₃ , this is the residue practically; as in atenolol, but with R _BI ^III = (XIe), with Y _BI = H, n = m = 0, R _BI ^IV = (XIi), this is the residue of butidrin, as in butetolol, but with S ₁ = -CN, this is the residue of bunitrolol, as in bufetolol, but with S ₁ = H, S ₄ = Cl, S ₂ = CH ₃ , this is the residue of bupranolol, as in bufetolol, but with S ₁ = -CO- (CH ₂ ) ₂ CH ₃ , S ₃ = F, this is the residue of butophylolol, as in bufetolol, but with R _BI ^IV = (XIp ^VII ), where A = -CH ₂ -CH ₂ -, B = -NH-, W2 = -O, which is with W1, representing a free valence, and a carbon atom in the G position forms a ketone group, this is a residue of carteolol; as in bufetolol, but with S ₃ = -NH-CO-N (C ₂ H ₅ ) ₂ , S ₁ = -CO-CH ₃ , this is the residue of celiprolol, as in bufetolol, but with S ₁ = -O-CH ₂ -CONH-CH ₃ , this is the remainder of cetamolol, as in bufetolol, but with S ₁ = cyclopentyl, this is the residue of penbutolol as in buftoolol, but with R _BI ^IV = (XIo), this is the residue of timolol, as in bufetolol, but with S ₁ = S ₂ = CH ₃ , it is the residue of xibenolol, as in bufetolol, but with R _BI ^IV = (XIt), it is the residue of bucumolol, as in bupranolol, but with S ₂ = Cl, it is the residue of chloranolol, as in butidrin, but with R _BI ^III = (XIe), with Y _BI = (XIf), with Z = H, R _BI ^IV = (XIp), where S ₃ = OH and S = CONH ₂ , S ₁ = S ₄ = H, this is the remainder Dilevalol as in Butydrin, but with R _BI ^III = CH ₃ , R _BI ^IV = (XIm), where the naphthalene residue is attached to the carbon atom in position 2 to provide the carbon atom with a substituent - OR _BI ^IV , it is pronethalol residue, as in carazolol, but with R _BI ^II = H and R _BI ^III = (XIb) is the carvedilol residue, as in carteolol, but in R _BI ^IV = (XIp ^VII ), A = -CH ₂ -, B = -COCH ₂ -, W1 = W2 = H, this is the residue of leftbunolol as in carteolol, but with R _BI ^I = H and in R _BI ^IV = (XIp ^VII ), A means a tertiary carbon atom and W1 means a free valence, resulting in a double bond —CH = CH- between A and the carbon atom in position 1 '(XIp ^VII ), W2 = CH ₃ , this is the residue of mepin dolola, as in carteolol, but in R _BI ^IV = (XIp ^VII ) A = -CH ₂ -CH (OH) -, B = -CH ₂ -, W2 = OH, W1 = H, this is the residue of nadolol, as in dilvalol , but with S ₂ = SOCH ₃ , and in para position to another aromatic ring (formula XIf) Z = -OCH ₃ , this is a sulfinalol residue, as in mepindolol, but in R _BI ^IV = (XIp ^VII ) A = -O- CH ₂ -, B = -CH ₂ -, W2 = -ONO ₂ , W1 = H, this is the residue of nipradilol, as in mepindolol, but with W2 = H, this is the residue of pindolol, as in nipradilol, but with R _BI ^I = CH ₃ , A = -S-CH ₂ - and W2 = H, this is the residue of tertatolol, as in pronethalol, but with m = 1 and X _BI = -O-, and R _BI ^IV is a naphthalene residue (XIm) attached by a carbon atom in 1 position to X _BI , this is the residue of propranolol, as in pronetholol, but with R _BI ^IV = (XIp) with S ₁ = S ₂ = S ₄ = H and S ₃ = -NH-SO ₂ -CH ₃ , this is the residue of sotalol, as in tertolol, but with R _BI ^IV = (XIn), it is tilisolol residue; as in xibenolol, but with R _BI ^I = S ₁ = H, this is the residue of toliprolol, as in toliprolol, but with R _BI ^II = H and R _BI ^III = (XIa), it is the residue of bevantolol, as in bevantolol, but with S ₂ = H, S ₁ = CN, R _BI ^III = (XIc), it is an epanolol residue, when in the formula (A3) R _BI ^I = R _BI ^II = R _BI ^III = CH ₃ , R _BI ^V (XIh), n = m = l, R _BI ^VI = R _BI ^VII = H, X _BI = -O-, R _BI ^IV = (XIg), this is the residue of bopindolol, when in the formula (A3) m = n = 0 and R _BI ^IV = (XIz) R _BI ^I = R _BI ^II = R _BI ^III = CH ₃ , R _BI ^V = H, this is the residue of bufurall when in formula (A3) R _BI ^I = R _BI ^II = H, R _BI ^III = (Xld ) with t = l, R _BI ^V = H, n = m = 0, R _BI ^IV = (XId) with t = 0, this is a residue of nebivolol, 2-hydroxy-5- [1-hydroxy-2 - [(1 -methyl-3-phenylpropyl) amino] ethyl] benzamide (la etalol), 1- (4-amino-6,7-dimethoxy-2-quinazolinyl) -4 - [(tetrahydro-2-furanyl) -carbonyl] piperazine (terazosin), 1- (4-amino-6,7- dimethoxy-2-quinazolinyl) -4- (2-furanylcarbonyl) piperazine (prazosin).

4. Nitrate salts according to claim 1 of the following compounds of class
(A4) (2S-cis) -3- (acetyloxy) -5- [2- (dimethylamino) ethyl] -2,3-dihydro-2- (4-methoxyphenyl) -1,5-benzothiazepin-4 (5H) -one (diltiazem), α- [3 - [[2- (3,4-dimethoxyphenyl) ethyl] methylamino] propyl] -3,4-dimethoxy-α- (1-methylethyl) benzene acetonitrile (verapamil);
(A4b) 3-ethyl-5-methyl ester 2 - [(2-aminoethoxy) methyl] -4- (2-chlorophenyl) -1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid (amlodipine), 4- (2,3-dichlorophenyl) -1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid ethyl methyl ester (felodipine), 4- (1-methyl) ethyl ester ( 4-benzofurazanil) -1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid (isradipine), lercanidipine, methyl-2 [methyl (phenylmethyl) amino] ethyl ester 1,4-dihydro-2,6 -dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid (nicardipine), 1,4-dihydro-2,6-dimethyl-4- (2-nitrophenyl) -3,5-pyridine dimethyl ester rboxylic acid (nifedipine), 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid (2-methoxyethyl-1-methylethyl ester) (methyl-2-methylpropyl ester) 1,4-dihydro-2,6-dimethyl-4- (2-nitrophenyl) -3,5-pyridinedicarboxylic acid (nisoldipine), 1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl ethyl methyl ester -3,5-pyridinedicarboxylic acid (nitrendipine);
(A4c) (E) -1- [bis (4-fluorophenyl) methyl] -4- (3-phenyl-2-propenyl) piperazine (flunarizin).

5. Nitrate salts according to claim 1 of the following compounds of class (A7):
(A7a) 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide (chlorothiazide), 2-chloro-5- (2,3-dihydro-1-hydroxy-3-oxo -1H-isoindol-1-yl) benzobesulphonamide (chlorothalidone), 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide (hydrochlorothiazide), 3- (aminosulphonyl ) -4-xnop-N- (2,3-dihydro-2-methyl-1H-indol-1-yl) benzamide (indapamide), 7-chloro-1,2,3,4-tetrahydro-2-methyl- 3- (2-methylphenyl) -4-oxo-6-quinazolin sulfonamide (metolazone), 7-chloro-2-ethyl-1,2,3,4-tetrahydro-4-oxo-6-quinazolin sulfonamide (quine tazone);
(A7d) 3,5-diamino-N- (aminoiminomethyl) -6-chloropyrazinecarboxamide (amiloride), 6-phenyl-2,4,7-pteridine triamine (triamterene), 3- (aminosulfonyl) -5- (butylamino) -4 -phenoxybenzoic acid (bumetanide), 5- (aminosulfonyl) -4-chloro-2 - [(2-furanylmethyl) amino] benzoic acid (furosemide), N - [[[(1-methylethyl) amino] -carbonyl] -4- [(3-methylphenyl) amino] -3-pyridinesulfonamide (torasemide).

6. Nitrate salts in PP. 1-5 of the following compounds: Class Alb): losartan, Class A2): sildenafil, zaprinast, Class A3): atenolol, labetalol, timolol, prazosin, terazosin, propanolol, Class A4): nicardipine, nifedipine, nimodipine, Class A7) chlorothiazide, amiloride, furosemide.

7. Nitrate salts in PP. 1-6, containing one or more isomers of the above compounds.

8. Nitrate salts in PP. 1-7, where the salts of the above compounds contain at least one mole of nitrate ions / mole of the compound.

9. Pharmaceutical compositions of nitrate salts in PP. 1-8.

10. Nitrate salts and pharmaceutical compositions according to claims. 1-9 for use as a medicine.

11. Nitrate salts and compositions according to claim 10, including salts and compositions of the following compounds in formula (A3), a compound is obtained when the substituents of the specified formula have the following meanings: R _BI ^I = R _BI ^II = CH ₃ ; n = 1; R _BI ^III = R _BI ^V = R _BI ^VI = R _BI ^VII = H; X _BI = O; R _BI ^IV is an aromatic ring (XIp) with S ₂ = S ₃ = S ₄ = H, S ₁ = CH ₂ -CH = CH ₂ (alprenolol), 6-phenyl-2,4,7-pteridinetriamin (triamterene); to obtain drugs for the treatment of hypertension.

12. Nitrate salts and compositions according to claim 11 for the preparation of medicaments, such as cardiovascular drugs.

13. Nitrate salts and compositions according to claim 11 for the preparation of drugs for relaxation of the cavernous artery and cavernous bodies of man.

14. Nitrate salts and compositions according to claim 13, where the compound is sildenafil nitrate.

15. Nitrate salts in PP. 1-8, containing in the molecule one group -ONO ₂ .