Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1998-03-17
1999-11-09
Spivack, Phyllis G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
A61K 31675
Patent
active
059815124
DESCRIPTION:
BRIEF SUMMARY
This application is PCT application AT96/00099 filed on May 30, 1996 which designated the U.S.
The present invention relates to the use of phosphorus derivatives of alkaloids for the preparation of a medicament for treating radiation injuries.
Austrian patent 377 988 and Austrian patent 354 644 describe methods for the preparation of new phosphorus derivatives of alkaloides and of new salts of alkaloid derivatives of thiophosphoric acid, respectively. Such compounds have a pharmacologic activity and can be used as cytostatic agents.
Compound ##STR1## is disclosed in AT 377988 in Example 1.
Surprisingly, it has now been found that the phosphorus derivatives of alkaloids, disclosed in Austrian patent 377 988 and Austrian patent 354 644, respectively, can be used for the preparation of medicaments for the treatment of radiation injuries as well as for the prevention of radiation injuries expected on account of radiation exposures.
Methods for the preparation of phosphorus derivatives of alkaloids of the general formula (I) ##STR2## wherein m and n=1, 2 or 3; R.sup.1, R.sup.2 and R.sup.3 are each independently H or methoxy, wherein R.sup.1 and R.sup.2, or R.sup.2 and R.sup.3 together also may represent a methylene dioxy group;
R.sup.4 and R.sup.5, together with the C atoms, to which they are attached, form an optionally totally or partially hydrogenated phenyl or naphthyl group, which in turn may be substituted by methoxy, hydroxy or dioxymethyl, wherein R.sup.7 is H or .dbd.O or an equal ring system bonded via a --CH.sub.2 --CO--CH.sub.2 chain, R.sup.6 is --CH.sub.3, and double bonds may be present in positions 1, 2 and/or 7, 8; or
R.sup.6 and R.sup.7 together with the C and N atoms, to which they are attached, form an optionally hydrogenated benzo or naphtho ring system, which in turn may be substituted by methoxy, oxo, methyl or dioxymethyl groups, wherein the C--N bond in positions 1, 2 may be missing, and R.sup.4 and R.sup.5 are H;
R.sup.10 =2H, --CH.sub.2 --CH.sub.2 --, H or --CH.sub.2 --CH.sub.2 Cl;
X=O or N;
R.sup.8 +R.sup.9 and R.sup.11 +R.sup.12 are --CH.sub.2 --CH.sub.2 -- and, if Y=S, X=N and n=2, R.sup.11 and R.sup.12 are --CH.sub.2 --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --O--CH--.sub.2 -- or ##STR3## if Y=S, X=N, n=2, R.sup.2 and R.sup.3 represent --CH.sub.2 --CH.sub.2 --, ##STR4## if Y=S, X=O, n=1, R.sup.3 is ##STR5## if Y=O, X=N, n=1, R.sup.3 is ##STR6## if Y=O, X=N, n=2, R.sup.11 and R.sup.12 are ##STR7## and if Y=O, X=O, n=1, R.sup.11 and R.sup.12 are each --CH.sub.2 --CH.sub.2 --Cl, R.sup.10 is H.sub.2 and R.sup.11 +R.sup.12 are --CH.sub.2 --CH.sub.2 -- or --CH.sub.2 --CH.sub.2 --CH.sub.2 --, if Y=S, X=N, R.sup.3 is --CH.sub.2 --CH.sub.2 --, as well as their salts with pharmaceutically compatible acids, are known from Austrian patent 377 988; the preparation of alkaloid derivatives of thiophosphoric acid of the general formula ##STR8## wherein n is 1, 2 or 3; m represents 1, 2 or 3; R.sup.1, R.sup.2 and R.sup.3 each independently are hydrogen or methoxy, wherein R.sup.1 and R.sup.2 or R.sup.2 and R.sup.3 together also may represent a methylene dioxy group; R.sup.4 is hydrogen, hydroxy or methyl; and, if R.sup.6 is hydrogen, R.sup.5 and R.sup.7 together form the group ##STR9## or, if R.sup.7 represents a methyl group, the groups R.sup.5 and R.sup.6 represent the group ##STR10## and in positions 1, 8 and/or 2, 3 there may be a double bond; and A is a monovalent or the equivalent portion of a polyvalent anion, is disclosed in Austrian patent 354 644.
According to a particularly preferred embodiment of the present invention, the reaction product of the alkaloids of Chelidonium maius L. with thiophosphoric acid triaziridide is used for the preparation of a medicament for the treatment or prevention in case of radiation injuries.
For reasons of simplicity, this reaction product will be named "Ukrain" in the following.
The surprising effect of Ukrain in the treatment or prevention of radiation injuries will be demonstrated in the following by way of a case description.
The following alkaloid componen
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