Aminodesoxy-1.4;3.6-dianhydrohexitol nitrates and pharmaceutical composition
AssigneeFirma Willmar Schwabe
InventorsKlaus Klessing, Shyam S. Chatterjee, Bernard L. Gabard
Life of this patent
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Abstract
Aminodesoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula I, ##STR1## wherein R.sup.1 and R.sup.2 possess the meanings given in claim 1, as well as their pharmacologically acceptable acid-addition salts; processes for the preparation of said compounds, and pharmaceutical compositions containing at least one of said compounds.
Claims85
Aminodesoxy-1.4;3.6-dianhydrohexitol nitrates of the general formula I, ##STR13## wherein R.sup.1 and R.sup.2, independently of one another, signify a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 an acyl residue of an aliphatic or singly unsaturated, possibly methyl-substituted monocarboxylic acid with 2 to 8 C-atoms, a nicotinoyl, 2-O-acetylsalicoyl radical or a 1-adamantyl radical;
- or wherein R.sup.1 signifies a hydrogen atom and R.sup.2 a 2-hydroxy-3-(subst.)-phenoxyprop-1-yl radical of the general formula Ia ##STR14## wherein R.sup.3 signifies a hydrogen atom, a lower alkyl or lower alkenyl group with 1 to 4 C-atoms, the trifluoromethyl radical, a hydroxyl group, a lower alkoxy or lower alkenyloxy group with 1 to 4 C-atoms, a cyano group or a carbamoylmethyl radical;
- or wherein R.sup.1
- signifies a hydrogen atom and R.sup.2 a 2-hydroxy-3-(.alpha.-naphthyloxy)-prop-1-yl radical, whereby the ring of the naphthalene skeleton which is not etherified with the hydroxypropyl group can be completely or partly hydrogenated or substituted by an oxo group;
- or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 an .omega.-(subst.)-phenylalkyl group of the general formula Ib ##STR15## wherein n can be=a whole number from 1 to 6 and R.sup.4 and R.sup.5, in each case independently of one another, signify a hydrogen atom, a lower alkyl or alkenyl group with 1 to 4 C-atoms, the trifluoromethyl radical, a hydroxyl group, a lower alkoxy or lower alkenyloxy group with 1 to 4 C-atoms or a fluorine or chlorine atom;
- or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 the diphenylmethyl radical or cinnamyl radical;
- or wherein R.sup.1 signifies a hydrogen atom or a lower alkyl group with 1 to 4 C-atoms and R.sup.2 an .omega.-(subst.)-phenoxyalkyl group of the general formula Ic ##STR16## wherein m can be=a whole number from 2-8 and R.sup.6 and R.sup.7, independently of one another, signify a hydrogen atom, a lower alkyl or lower alkenyl group while 1 to 4 C-atoms, the trifluoromethyl radical, a hydroxyl group, a lower alkoxy or lower alkenyloxy group with 1 to 4 C-atoms, a fluorine or chlorine atom, the amino or acetylamino group, a mono- or di-lower alkylamino group with 1 to 4 C-atoms or R.sup.6 and R.sup.7, together with the phenyl radical, form the .alpha.-naphthyl radical;
- or wherein R.sup.1 and R.sup.2, together with the nitrogen atom to which they are attached, represent the residue of a cyclic, non-aromatic secondary amine with 5 to 7 ring atoms which possibly contains a furher hetero atom;
- or wherein R.sup.1 and R.sup.2 together signify a pyridoxylidene radical;
- as well as their pharmacologically acceptable acid-addition salts.
5-Amino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Amino-5-desoxy-1.4;3.6-dianhydro-D-glucitol 2-nitrate.
2-Amino-2-desoxy-1.4;3.6-dianhydro-D-glucitol 5-nitrate.
5-Amino-5-desoxy-1.4;3.6-dianhydro-D-mannitol 2-nitrate.
5-Pivaloylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2 nitrate.
5-Acetylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Nicotinoylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(2-Acetoxybenzoylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Methylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Ethylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Adamant-1-ylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Dimethylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Diethylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Pyrrolidino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Piperidine-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Morpholino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(4-Methylpiperazino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Pyridoxylideneamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(N-Benzyl-N-methylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[N-(2-Phenylethyl)-N-methylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[N-Me thyl-N-(3-phenylpropyl)-amino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[N-(4-Phenylbutyl)-N-methylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[N-Me thyl-N-(5-phenylpentyl)-amino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(N-Cinnamyl-N-methylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Benzylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Diphenylmethylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(2-Phenylethylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(3-Phenylpropylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(4-Phenylbutylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(5-Phenylpentylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(3,4-Dimethoxyphenyl)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-id itol 2-nitrate.
5-[4-(4-Methoxyphenyl)-butylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[N-(2 -Phenoxyethyl)-N-methylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate
5-[N-Methyl-N-(3-phenoxypropyl)-amino]-5-desoxy-1.4;3.6-dianhydro-L-idi tol 2-nitrate.
5-(2-Phenoxyethylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(3-Phenoxypropylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(4-Phenoxybutylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(5-Phenoxypentylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(6-Phenoxyhexylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(7-Phenoxyheptylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-(8-Phenoxyoctylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
2-(3-Phenoxypropylamino)-2-desoxy-1.4;3.6-dianhydro-D-glucitol 5-nitrate.
2-(4-Phenylbutylamino)-2-desoxy-1.4;3.6-dianhydro-D-glucitol 5-nitrate.
5-[2-Hydroxy-3-(4-methoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhyd ro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(3- methoxyphenoxy)-propylamino)-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(2-methoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhyd ro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(2- ethoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(2-allyloxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhy dro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(2-a llylphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(2-cyanophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro -L-iditol 2-nitrate.
5-[2-Hydroxy-3-( 3-tolyloxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(3-trifluoromethylphenoxy)-propylamino]-5-desoxy-1.4;3.6 -dianhydro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(4-carbamoy lmethylphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(1-naphthyloxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro- L-iditol 2-nitrate.
5-[2-Hydroxy-3- (1-naphthyloxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-D-glucitol 2-nitrate.
5-[2-Hy droxy-3-(1-oxo-1.2.3.4-tetrahydro-5-naphthyloxy)-propylamino]-5-desoxy-1.4;
- 3.6-dianhydro-L-iditol 2-nitrate.
5-[2-Hydroxy-3-(5.6.7.8-tetra hydro-1-naphthyloxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(3 -Trifluoromethylphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(4-Tolyloxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(4-Fluorophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(1-Naphthyloxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(4 -Methoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate .
5-[3-(3-Methoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-idito l 2-nitrate.
5-[3-(2- Methoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(2,6-Dimethoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-i ditol 2-nitrate.
5-[3-(3,5-Di methoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[2,3-Dimethoxyphenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-idit ol 2-nitrate.
5-[3-(4-Chlorophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(2-Chlorophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(3-Chlorophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(3 ,4-Dichlorophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(2 ,4-Dichlorophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(4 -Acetamidophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(3 -Dimethylaminophenoxy)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[3-(4-Chlorophenyl)-propylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-[4-(4-Chlorophenyl)-butylamino]-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
5-Nicotinoylamino-5-desoxy-1.4;3.6-dianhydro-D-mannitol 2-nitrate.
5-N-Methyl-N-nicotinoylamino-5-desoxy-1.4;3.6-dianhydro-L-iditol 2-nitrate.
Dependencies are inferred from the claim text.