Imidazole derivatives, their preparation and their use as S-aden

Details Imidazole derivatives, their preparation and their use as S-aden Imidazole derivatives, their preparation and their use as S-aden

1997-07-23

1998-11-24

Clardy, S. Mark

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

5483315, 5483325, 514398, C07D23388, C07D23346, A61K 31415

Patent

active

058409114

DESCRIPTION:

BRIEF SUMMARY
This application has been filed under 35 USC 371 as a National Stage application of PCT/EP 96/00143, filed Jan. 15, 1996.


BRIEF DESCRIPTION OF THE INVENTION

The invention relates to novel imidazole derivatives, to tautomers thereof and/or to salts thereof, to a process for the preparation of those compounds, to pharmaceutical compositions comprising those compounds, and to
a) those compounds for use in, or
b) the use of those compounds for, the therapeutic treatment of the human or animal body; and/or to the use of those compounds in the preparation of pharmaceutical compositions.


BACKGROUND OF THE INVENTION

It is known that inhibition of S-adenosylmethionine decarboxylase can be used for therapeutic purposes. Surprisingly, a novel class of compounds having valuable pharmacological properties has now been found.


COMPLETE DESCRIPTION OF THE INVENTION

An imidazole derivative according to the invention is especially a compound of formula I ##STR2## wherein
R.sub.1 is hydrogen or hydroxy;
R.sub.2, R.sub.2 ' and R.sub.2 " are each independently of the others hydrogen or a substituent other than hydrogen;
either
R.sub.3 is hydrogen or a substituent other than hydrogen and
R.sub.4 is hydrogen or lower alkyl,
R.sub.3 and R.sub.4 together form a divalent radical of the formula --(CH.sub.2),-- wherein n is 2 or 3;
R.sub.5 and R.sub.6 are each independently of the other hydrogen, alkyl or aryl; and either R.sub.7 and R.sub.8 are each hydrogen, or R.sub.7 and R.sub.8 together form a bond; a tautomer thereof, provided that at least one tautomerisable group is present; or a salt thereof.
Within the scope of the present Application, the general terms used hereinbefore and hereinafter have preferably the following meanings (unless indicated otherwise):
The term "lower" denotes a radical having up to and including a maximum of 7 carbon atoms, preferably up to and including a maximum of 4 carbon atoms.
Lower alkyl is, for example, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, n-hexyl or n-heptyl, or, preferably, ethyl or, especially, methyl.
A substituent other than hydrogen is especially lower alkyl, halo-lower alkyl having one or more, preferably up to three, halogen atoms, cycloalkyl, aryl-lower alkyl, hydroxy, lower alkoxy, aryl-lower alkoxy, aryloxy, acyloxy, such as lower alkanoyloxy or arylcarbonyl-oxy, halogen, amino, N-lower alkylamino, N,N-di(lower alkyl)amino, acylamino, such as lower alkanoylamino or arylcarbonylamino, nitro, lower alkanoyl, arylcarbonyl, carboxy, lower alkoxycarbonyl, aryl-lower alkoxycarbonyl, such as 1-aryl-lower alkoxycarbonyl, for example benzyloxycarbonyl, carbamoyl (--CONH.sub.2), N-lower alkylcarbamoyl, N,N-di-(lower alkyl)carbamoyl, N-arylcarbamoyl, cyano, mercapto, lower alkylthio, lower alkanesulfonyl, sulfamoyl (--SO.sub.2 NH.sub.2), N-lower alkylsulfamoyl or N,N-di(lower alkyl)sulfamoyl.
Halo-lower alkyl is especially mono-, di- or tri-(halo)-lower alkyl, such as trifluoromethyl.
Halogen is, for example, iodine or, preferably, bromine or, especially, fluorine or chlorine.
Cycloalkyl is preferably C.sub.3 -C.sub.8 cycloalkyl (having from 3 to 8 ring carbon atoms) and especially C.sub.5 -C.sub.6 cycloalkyl (having 5 or 6 ring carbon atoms), it being possible for cycloalkyl to be unsubstituted or substituted by lower alkyl.
Aryl is preferably an aromatic ring system having from 6 to 12 ring carbon atoms that is unsubstituted or substituted by one or more substituents of any kind selected independently of one another, and is bi- or, preferably, mono-cyclic; especially unsubstituted or substituted phenyl or naphthyl, such as 1- or 2-naphthyl; suitable substituents being preferably one or more, especially from one to three, more especially one or two, radicals selected independently of one another from the group consisting of lower alkyl, phenyl, naphthyl, such as 1- or 2-naphthyl, lower alkoxy, hydroxy, lower alkanoyloxy, nitro, amino, halogen, halo-lower alkyl, such as trifluoromethyl, carboxy, lower alkoxycarbonyl, carbamoyl, N-lower alkyl

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