SI8911762B - Novel organic nitrates and a process for their preparation - Google Patents

Claims (8)

A process for the preparation of compounds and their pharmaceutically acceptable salts, characterized in that the compound of the corresponding nitrate fatty acids of general formula (A) is 0 o RL m (A) in the form of a Member from the group consisting of free acid, reactive halide, azide, ester and / or anhydride, reacts with the amino group of a compound of general formula (B) R ~ R HN— (CH2- ) n — C— (CH2) q- -R (B) R- to make a compound of general formula (I) (.¾) nr '-CCSTo) L · · O 0 1 c — R · (I) which is optionally alkylated on the side chain with an O ^ -03 group and wherein in general formulas (A), (B) ) and (I) represent: -2-R hydroxy, C 1 -C 6 -alkoxy, amino; 1 R is hydrogen, alkyl of 1 to 4 carbon atoms, R is hydrogen or methyl; R3 is hydrogen; R4 is hydrogen; R3 is mercaptomethyl, mercaptoethyl, methylthioethyl, its S-acyl derivatives, in particular S-acetate, S-propionate, S-butyrate, S-caproate, S-caprylate, S-isobutyrate, S-pivalate, S-benzoate; groups in which R and R5 are bonded together in the form of a thiolactone, groups in which R and R4 are bonded together in the form of an ester or amide, groups in which R3 and R4 are bonded together in the form of an alkylene bridge with 2 up to 4 carbon atoms, an alkylene bridge with 2 to 3 carbon atoms and a sulfur atom, an alkylene bridge with 3 to 4 carbon atoms containing a double bond or an alkylene bridge, as mentioned above, which may be substituted by an article from the group consisting of hydroxy, m, n and o are integers from 0 to 10. Process according to Claim 1, characterized in that fatty acid nitrate of a length of C2 to Cg is used, which can be linear or branched, racemic or optical. Process according to Claim 1 or 2, characterized in that cysteine, methionine or homocysteine is used as the amino acid. Process according to one of Claims 1 to 3, characterized in that stereochemically L-shaped acids are used as amino acids. Process according to one of Claims 1 to 4, characterized in that cysteine and / or methionine in the form of methyl, ethyl or propyl ester are used as amino acids. Process according to one of Claims 1 to 5, characterized in that cysteine is used which is esterified on the SH group with alkanecarboxylic acids with 2-8 C atoms. Process for the preparation of compounds according to Claims 1 to 6, characterized in that suitable starting materials are used which give the following compounds which correspond to the general formula (I): N- (2-nitroacetyl) -cysteine ethyl ester N N- (2-nitratoacetyl) -S-propionyl-cysteine ethyl ester N- (2-nitratoacetyl) -S-pivalyl-cysteine ethyl ester N- (2- (nitrotoacetyl) -S-acetyl-cysteine ethyl ester N- (2-) N- (2-nitratopropionyl) -cysteine N- (2-nitratopropionyl) -methionine ethyl ester N- (2-nitrotobutyryl) -cysteine N- (2-nitratopropionyl) -cysteine N- (2-Nitratobutyryl) -S-butyryl-cysteine ethyl ester N- (2-nitrobutyryl) -methionine ethyl ester N- (2-nitratobutyryl) -S-acetyl-cysteine ethyl ester N- (2-nitratoisobutyryl) -S-benzoyl-cisteine ethyl ester N- (2-nitroisobutyryl) -S-acetyl-cysteine ethyl ester N- (2-nitro) N- (2-nitrotoisobutyryl) -S-pivanyl-1-cystine ethyl ester N- (3-nitratobutyryl) -cysteine N- (3-nitrobutyryl) -cysteine N- (3-nitrobutyryl) -S-acetyl-cysteine ethyl ester N- (3-nitrobutyryl) -S N- (3-Nitrotopivaloyl) - and N- (3-nitrophonyl ethyl ester N- (3-nitratobutyryl) -methionine ethyl ester -4-N- (3-nitrophobutyryl) -homocysteine-thio-1-acetone N- (3-nitro soluble oyl) -S-acetyl-cysteine ethyl ester N- (3-nitro soluble oi1) -nitratopival oyl) -cysteine ethyl ester N- (3-nitro soluble oi1) -cysteine ethyl ester-S-carbonate N- (3-nitratopival oyl) -S-butyryl-cysteine ethyl ester N- (3-nitratopival oyl) -S-isobutyryl-cystine ethyl ester N- (3-nitratopival oi1) -S-propionyl-cysteine ethyl ester N- (3-nitratopival oyl) -S-pivaloyl-cystine ethyl ester N- (3-nitratopival oyl) -S-benzoyl-cysteine ethyl ester N- (3-nitratopival oyl) -methionine ethyl ester N- (3-nitratopival oyl) -methionine N N- (2-nitrotohexanoyl) -cysteine ethyl ester N- (2-nitratohexanoyl) -S-propionyl-cysteine ethyl ester N- (3-nitrate) - (3-nitrotopivaloyl) -homocysteine-thio-lactone N- (3-nitratolauroyl) -cystine and N- (12-nitratolauroyl) -cysteine ethyl ester N- (12-nitratolauroyl) -S- acetyl-cysteine N- (12-nitratolauroyl) -S-pivaloyl-cysteine Process for the manufacture of pharmaceutical compositions, characterized in that as active ingredient a compound or mixture of compounds according to claims 1 to 7 and / or derivatives and / or pharmaceutically acceptable salts thereof containing pharmaceutical carriers are incorporated into a pharmaceutical composition. shape. For SCHWARZ PHARMA AG Monheim / RHLD, Germany: