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US 5,665,886 AGranted
Salts of substituted nitrogenous heteroaromatic compounds, a process for their preparation and pharmaceutical compositions containing them
AssigneeSanofi
InventorsNathalie Chabert, Xavier Emonds-Alt, Vincenzo Proietto, Didier Van Broeck
Life of this patent
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Abstract
The invention concerns compounds of formula: ##STR1## in which Am.sup.+ represents a substituted 1-pyridylium radical, a substituted 3-thiazolylium radical, a substituted 1-pyridazinylium radical or a substituted 3-imidazolylium radical, and their salts with mineral or organic acids, whether in their optically pure or racemic form. The invention also concerns a process for the preparation of these compounds and pharmaceutical compositions containing them. Activity: antagonists of neurokinin receptors.
Claims11
A compound of formula ##STR27## in which:
- Ar represents an aromatic or heteroaromatic mono-, di- or tricyclic group which may be substituted;
- T represents a direct bond;
- a hydroxymethylene group;
- a (C.sub.1 -C.sub.4)alkoxymethylene group;
- a (C.sub.1 -C.sub.5)alkylene group;
- an oxygen atom;
- a --NR.sub.3 group;
- a vinylene group;
- Ar' represents phenyl which may be unsubstituted or substituted one or more times by a substituent selected from:
- a halogen atom, trifluoromethyl, hydroxy, (C.sub.1 -C.sub.4)alkoxy, (C.sub.1 -C.sub.4)alkyl, said substituents being identical or different;
- thienyl;
- benzothienyl;
- naphthyl;
- indolyl which may be N-substituted by a (C.sub.1 -C.sub.4)alkyl or benzyl;
- R.sub.1 represents hydrogen;
- (C.sub.1 -C.sub.4)alkyl;
- .omega.-hydroxy-(C.sub.2 -C.sub.4)alkylene;
- .omega.-(C.sub.1 -C.sub.4)alkoxy-(C.sub.2 -C.sub.4)alkylene;
- .omega.-benzyloxy-(C.sub.2 -C.sub.4)alkylene;
- .omega.-formyloxy-(C.sub.2 -C.sub.4)alkylene;
- .omega.-(C.sub.1 -C.sub.4)alkylcarbonyloxy-(C.sub.2 -C.sub.4)alkylene;
- .omega.-benzoyloxy-(C.sub.2 -C.sub.4)alkylene;
- .omega.-R.sub.6 NHCOO--(C.sub.2 -C.sub.4)alkylene;
- .omega.-(C.sub.1 -C.sub.4)alkylthio-(C.sub.2 -C.sub.4)alkylene;
- .omega.-carboxy-(C.sub.2 -C.sub.4)alkylene;
- .omega.-(C.sub.1 -C.sub.4)alkoxycarbonyl-(C.sub.2 -C.sub.4)alkylene;
- .omega.-R.sub.7 R.sub.8 NCO--(C.sub.2 -C.sub.4)alkylene;
- .omega.-R.sub.9 R.sub.10 N--(C.sub.2 -C.sub.4)alkylene;
- .omega.-R.sub.11 CONR.sub.12 --(C.sub.2 -C.sub.4)alkylene;
- .omega.-R.sub.13 OCONR.sub.12 --(C.sub.2 -C.sub.4)alkylene;
- .omega.-R.sub.7 R.sub.8 NCONR.sub.12 --(C.sub.2 -C.sub.4)alkylene;
- .omega.-R.sub.14 SO.sub.2 NR.sub.12 --(C.sub.2 -C.sub.4) alkylene;
- .omega.-(C.sub.1 -C.sub.4)alkylcarbonyl-(C.sub.2 -C.sub.4)alkylene;
- .omega.-cyano-(C.sub.1 -C.sub.3)alkylene;
- R.sub.2 represents hydrogen;
- or R.sub.1 and R.sub.2 together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group;
- R.sub.3 represents hydrogen or (C.sub.1 -C.sub.4)alkyl;
- Am.sup.+ represents a substituted 1-pyridylium radical of formula:
- ##STR28## R.sub.4 represents a group:
- ##STR29## W represents a direct bond;
- a methylene group;
- an oxygen atom;
- a sulfur atom;
- a --NR.sub.3 --group;
- R.sub.5 represents hydrogen;
- a halogen;
- hydroxy;
- (C.sub.1 -C.sub.4)alkoxy;
- (C.sub.1 -C.sub.4)alkyl;
- trifluoromethyl;
- R.sub.6 represents (C.sub.1 -C.sub.7)alkyl or phenyl;
- R.sub.7 and R.sub.8 each independently represent hydrogen or (C.sub.1 -C.sub.7)alkyl;
- R.sub.8 may also represent (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.3 -C.sub.7)cycloalkylmethyl, phenyl or benzyl;
- or R.sub.7 and R.sub.8 together with the nitrogen atom to which they are bound constitute a heterocycle selected from azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine or perhydroazepine;
- R.sub.9 and R.sub.10 each independently represent hydrogen or a (C.sub.1 -C.sub.7)alkyl;
- R.sub.10 may also represent (C.sub.3 -C.sub.7)cycloalkyl-methyl or benzyl;
- R.sub.11 represents hydrogen, (C.sub.1 -C.sub.7)alkyl, vinyl, phenyl, benzyl, pyridyl or (C.sub.3 -C.sub.7)cycloalkyl which may be unsubstituted or substituted by one or more methyl groups;
- R.sub.12 represents hydrogen or (C.sub.1 -C.sub.7)alkyl;
- R.sub.13 represents (C.sub.1 -C.sub.7)alkyl or phenyl;
- R.sub.14 represents (C.sub.1 -C.sub.7)alkyl;
- a free amino group or an amino group substituted by one or two (C.sub.1 -C.sub.7)alkyls;
- phenyl which may be unsubstituted or substituted one or more times by a substituent selected from:
- a halogen atom, (C.sub.1 -C.sub.7)alkyl, trifluoromethyl, hydroxy, (C.sub.1 -C.sub.7)alkoxy, carboxy, (C.sub.1 -C.sub.7)alkoxycarbonyl, (C.sub.1 -C.sub.7)alkylcarbonyloxy, cyano, nitro, a free amino group or an amino group substituted by one or two (C.sub.1 -C.sub.7)alkyls, said substituents being identical or different;
- m is 2 or 3;
- A.sup.- is an anion;
- and its salts with mineral or organic acids, in an optically pure or a racemic form.
63 more elements
Dependencies are inferred from the claim text.