Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Patent
1991-04-22
1995-03-28
Dees, Jose G.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
514538, 514547, 514551, 514561, 560170, 562444, C07C22912, A61K 31195
Patent
active
054018757
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Protein kinase C plays an important role in intracellular signal transduction and is closely connected with the regulation of contractile, secretory, and proliferative processes (Y. Nishizuka, Nature 308:693-698, 1984).
SUMMARY OF THE INVENTION
The invention concerns a compound of formula ##STR2## or a pharmaceutically acceptable salt thereof wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are as described below.
Preferred compounds of the instant invention are those wherein
R.sup.1 is octyl or octadecyl,
R.sup.2 and R.sup.3 are each independently hydrogen or methyl,
R.sup.4 is hydroxymethyl, hydroxyethyl, hydroxybenzyl, or ethoxycarbonyl, and
R.sup.5 is hydrogen or ethyl.
More preferred compounds of the instant invention are those named:
2-[N-methyl-N-(3-octadecyloxy-2-hydroxypropyl)]-amino-3-hydroxypropionic acid hydrochloride;
2-[N-methyl-N-(3-octyloxy-2-hydroxypropyl)]-amino-3-hydroxypropionic acid;
2-[N-methyl-N-(3-octadecyloxy-2-hydroxypropyl)]-amino-3-hydroxypropionic acid ethyl ester;
(.+-.)-2-N-(3-octadecyloxy-2-hydroxypropyl)-aminoacetic acid hydrochloride;
2-N-(3-octadecyloxy-2-hydroxypropyl)amino-3-hydroxypropionic acid hydrochloride;
2-N-(3-octadecyloxy-2-methoxypropyl)aminopropionic acid ethyl ester oxalate;
2-N-(3-octadecyloxy-2-methoxypropyl)-amino-3-hydroxybutyric acid;
2-N-(3-octadecyloxy-2-hydroxypropyl)aminomalonic acid diethyl ester;
2-N-(3-octadecyloxy-2-hydroxypropyl)-amino-3-phenylpropionic acid.
The invention also concerns a pharmaceutical composition for the prevention and/or treatment of heart and blood vessel diseases, inflammatory diseases, allergies, cancers, viral diseases, and degenerative diseases of the central nervous system comprising a therapeutically effective amount of a compound according to formula I below wherein R.sup.4 is defined as hydrogen, methyl, hydroxyalkyl, benzyl, hydroxybenzyl, carboxyl, or alkoxycarbonyl in combination with a pharmaceutically acceptable carrier.
The invention also concerns methods of treating and methods of preventing heart and blood vessel diseases, inflammatory diseases, allergies, cancers, vital diseases, and degenerative diseases of the central nervous system in a patient suffering therefrom comprising administering to said patient a therapeutically effective amount of a composition as above in unit dosage form.
DETAILED DESCRIPTION
The instant invention concerns new 2-aminocarboxylic acids and derivatives of formula ##STR3## and the pharmaceutically acceptable salts thereof wherein R.sup.1 is a straight-chained or branched, saturated or unsaturated alkyl group of from 1 to 20 carbon atoms, R.sup.2 and R.sup.3, which may be the same or different, are hydrogen or a straight-chained or branched alkyl group with from 1 to 4 carbon atoms, R.sup.4 is hydroxybenzyl, a carboxyl group, a hydroxyalkyl or alkoxycarbonyl group from 1 to 4 carbon atoms each, and R.sup.5 is hydrogen or a straight-chained or branched alkyl group with from 1 to 4 carbon atoms.
Preferred compounds of the invention are those of formula I where R.sup.1 is octyl- or octadecyl, R.sup.2 and R.sup.3, which may be the same or different, are hydrogen or methyl, R.sup.4 is hydroxymethyl, hydroxyethyl, hydroxybenzyl or ethoxycarbonyl, and R.sup.5 is hydrogen or lower alkyl with of from 1 to 4 carbon atoms.
More preferred compounds of the invention are:
2-[N-methyl-N-(3-octadecyloxy-2-hydroxypropyl)]-amino-3-hydroxypropionic acid hydrochloride;
2-[N-methyl-N-(3-octyloxy-2-hydroxypropyl)]-amino-3-hydroxypropionic acid;
2-[N-methyl-N-(3-octadecyloxy-2-hydroxypropyl)]-amino-3-hydroxypropionic acid ethyl ester;
(.+-.)-2-N-(3-octadecyloxy-2-hydroxypropyl)-aminoacetic acid hydrochloride;
2-N-(3-octadecyloxy-2-hydroxypropyl)-amino-3-hydroxypropionic acid hydrochloride;
2-N-(3-octadecyloxy-2-methoxypropyl)-aminopropionic acid ethyl ester oxalate;
2-N-(3-octadecyloxy-2-methoxypropyl)amino-3-hydroxybutyric acid;
2-N-(3-octadecyloxy-2-hydroxypropyl)-aminomalonic acid diethyl ester;
2-N-(3-octadeycyloxy-2-hydroxypropyl)-amino-3-phenylpropionic a
REFERENCES:
patent: 3647868 (1972-03-01), Ernst
patent: 3778268 (1973-12-01), Ushiyama et al.
patent: 4309327 (1982-01-01), Ishikura et al.
patent: 4358368 (1982-11-01), Hellsten et al.
patent: 4450173 (1984-05-01), Erhardt et al.
David Bradshaw et al., "Therapeutic Potential of Protein Kinase C Inhibitors", Agents Actions 38 (1993), pp. 135-147.
Chemical Abstracts, vol. 66, Apr. 10, 1967, pp. 6335, 67040u.
Chemical Abstracts, vol. 104, Jun. 16, 1986, p. 201, 210577k.
Hartenstein Johannes
Osswald Hartmut
Rudolph Claus
Schachtele Christoph
Trostmann Uwe
Anderson Elizabeth M.
Dees Jos,e G.
Frazier B.
Godecke Aktiengesellschaft
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