Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1995-08-18
1997-05-06
Dees, Jose G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514659, 514660, 564512, 564455, 564457, 564461, 564462, A61K 3113, C07C21122, C07C21125
Patent
active
056272154
DESCRIPTION:
BRIEF SUMMARY
This application is filed under 35 U.S.C. .sctn.371 as a national phase application of PCT/EP94/04230, filed Dec. 14, 1994, which was based on Switzerland Application No. 3876/93-9, filed Dec. 27, 1993.
The invention relates to N.sup.1,N.sup.14 -disubstituted tetraazatetradec-7-enes and their salts, to processes for the preparation of those compounds, to pharmaceutical compositions comprising those compounds, and to the use of those compounds in the therapeutic treatment of the human or animal body or in the preparation of pharmaceutical compositions.
Polyamines, for example spermine, spermidine and analogues thereof, have for some time been the subject of intensive investigation as regards their biological properties, especially as regards proliferative processes. An early finding has been that higher levels of polyamines are to be found in cells that are dividing, for example in cancer cells, than in cells that are stable.
Such phenomenological observations have led to the conclusion that polyamines are necessary for cell proliferation.
The concept of influencing the polyamine level in cells has therefore been made use of in chemotherapy, for example of cancerous diseases.
Surprisingly, it has now been found that the compounds of the present invention have especially valuable properties that can be used pharmacologically.
The compounds according to the invention are compounds of formula I ##STR2## wherein R.sub.1 and R.sub.2, each independently of the other, are selected from lower alkyl that is unsubstituted or substituted by one or more fluorine atoms which are not linked to the carbon atom of R.sub.1 or R.sub.2 bonding the nitrogen; from lower alkenyl wherein the double bond does not originate from the carbon atom that is bonded to a nitrogen bonding R.sub.1 or R.sub.2 ; from lower alkynyl wherein the triple bond does not originate from the carbon atom that is bonded to a nitrogen bonding R.sub.1 or R.sub.2 ; from cycloalkyl; and from cycloalkyl-lower alkyl; with the proviso that not more than one of the two radicals R.sub.1 and R.sub.2 is methyl; or salts thereof.
Within the context of the present Application, the general terms used hereinbefore and hereinafter have preferably the following meanings:
Lower alkyl has especially up to a maximum of 7 carbon atoms, is branched or unbranched and is preferably methyl or especially C.sub.2 -C.sub.7 alkyl, such as ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, n-hexyl or n-heptyl, especially methyl or more especially C.sub.2 -C.sub.4 alkyl, such as ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or isobutyl, with ethyl and propyl, such as n-propyl, being especially preferred.
Those radicals are preferably unsubstituted but may also be substituted by one or more, preferably up to three, fluorine atoms, for example as in 2,2,2-trifluoroethyl. The fluorine atom is not bonded to the carbon atom in R.sub.1 or R.sub.2 that is bonded to the nitrogen in formula I.
Lower alkenyl has especially from 3 to 7, preferably 3 or 4, carbon atoms and is, for example, allyl or crotyl.
Lower alkynyl has especially from 3 to 7, preferably 3 or 4, carbon atoms and is, for example, propyn-2-yl or 2-butyn-1-yl.
In lower alkenyl and lower alkynyl, an unsaturated bond must not originate from the carbon atom that is bonded to a nitrogen atom bonding R.sub.1 or R.sub.2, as unstable compounds are otherwise formed.
Cycloalkyl has preferably from 3 to 7, especially from 3 to 5, carbon atoms and is especially cyclopropyl or cyclobutyl.
Cycloalkyl-lower alkyl contains as cycloalkyl especially a radical having from 3 to 5 carbon atoms, especially cyclopropyl or also cyclobutyl, and as lower alkyl radical preferably a radical as defined above, especially C.sub.1 -C.sub.3 alkyl, for example methyl, ethyl, n-propyl or isopropyl, more especially C.sub.1 -C.sub.2 alkyl. Preference is given to 2-cyclopropylethyl, cyclobutyl-methyl or, especially, cyclopropylmethyl.
On account of their basic properties, salts of compounds of formula I are especially acid a
REFERENCES:
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Frei Jorg
Stanek Jaroslav
Ciba-Geigy Corporation
Dees Jos,e G.
Kaiser Karen G.
Lambkin Deborah
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