Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-09-15
1998-11-10
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514316, 546186, 546246, A61K 31445, C07D21126, C07D21134, C07D21160
Patent
active
058344861
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP96/00898, filed 4 Mar. 1996.
BRIEF DESCRIPTION OF THE INVENTION
The invention relates to novel cyclic polyamine analogues that are derivatives of propane- or butane-diamine, and to salts thereof, 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 and in the preparation of pharmaceutical compositions.
BACKGROUND TO THE INVENTION
The enzymes that are involved in the metabolism of polyamines, such as S-adenosyl-methionine decarboxylase (SAMDC) and ornithine decarboxylase (ODC), are the subject of intensive research. The background is that polyamines, such as spermine, spermidine and analogues thereof, play an important part in cell division and regulatory phenomena, for example in eukaryotic cells.
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 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 recognized and made use of in chemotherapy, for example of cancerous diseases.
Surprisingly, it has now been found that the compounds of the present invention exhibit especially valuable properties that can be used pharmacologically.
COMPLETE DESCRIPTION OF THE INVENTION
The compounds according to the invention are compounds of formula (I) ##STR2## wherein either R.sub.1 is hydrogen and
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, special preference being given to ethyl and propyl, such as n-propyl.
Lower alkenyl has especially from 3 to 7, preferably 3 or 4, carbon atoms and has one or (less preferably) more double bonds. Preference is given, for example, to allyl or crotyl.
Lower alkynyl has especially from 3 to 7, preferably 3 or 4, carbon atoms and has one or (less preferably) more triple bonds. Preference is given, for example, to propyn-2-yl or 2-butyn-1-yl.
In lower alkenyl and lower alkynyl R.sub.2, no unsaturated bonds originate from the carbon atom that is bonded to the nitrogen atom bonding R.sub.2, since unstable compounds are otherwise formed.
Tetramethylene formed by R.sub.1 and R.sub.2 is --(CH.sub.2).sub.4 -- and is bonded at both its terminal carbon atoms.
Salts are especially the pharmaceutically acceptable, that is to say non-toxic, salts of compounds of formula (I), that is to say especially the corresponding acid addition salts with acid anions that are not toxic (at the dose in question).
Such salts are formed, for example, by compounds of formula (I) with inorganic acids, for example hydrohalic acids, such as hydrochloric acid or hydrobromic acid, sulfuric acid or phosphoric acid, or with organic carboxylic, sulfonic, sulfo or phospho acids or N-substituted sulfamic acids, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid, and also with amino acids, such as the 20 .alpha.-amino acids involved in the synthesis of proteins in nature, for example glutamic acid or aspartic acid, as well as with methanesulfonic acid, ethanesulfonic acid, 2-hydr
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Frei Jorg
Stanek Jaroslav
Borovian Joseph J.
Kight John
M. Mach D. Margaret
Novartis AG
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