Patent ID: 6303626
Filing Date: 2001-10-16
Classification: A61K,A61P

Abstract:
A pharmaceutical formulation, presented in dry form, for the oral administration of an active principle of the formula ##STR10##in which:A.sup..crclbar. is a pharmaceutically acceptable anion;Am.sup..sym. is:i--either a group Am.sub.1.sup..sym. of the formula ##STR11##in which:Ar.sub.1 is a phenyl which is unsubstituted or monosubstituted or polysubstituted by a substituent selected from a halogen atom, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, a (C.sub.1 -C.sub.4)alkyl and a trifluoromethyl, said substituents being identical or different;x is zero or one;W.sub.1 is a (C.sub.1 -C.sub.6)alkyl or a benzyl group, the substituent W.sub.1 being either in the axial position or in the equatorial position;ii--or a group Am.sub.2.sup..sym. of the formula ##STR12##in which:Ar.sub.1, x and W.sub.1 are as defined above; andR.sub.1 is a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, a formyloxy, a (C.sub.1 -C.sub.3)alkhylcarbonyloxy, a carboxyl, a (C.sub.1 -C.sub.4)alkoxycarbonyl, a cyano, a (C.sub.1 -C.sub.3)alkylcarbonylamino, a mercapto or a (C.sub.1 -C.sub.4)alkylthio;iii--or a group Am.sub.3.sup..sym. of the formula ##STR13##in which:Ar.sub.1 and W.sub.1 are as defined above;R.sub.2 is hydrogen, a (C.sub.1 -C.sub.3)alkyl, a (C.sub.1 -C.sub.3)alkylcarbonyl;iv--or a group Am.sub.4.sup..sym. of the formula ##STR14##in which:Ar.sub.1 and x are as defined above; andp is one or two;v--or a group Am.sub.5.sup..sym. of the formula ##STR15##in which:Ar.sub.1 and x are as defined above;Ar is a phenyl which is unsubstituted or monosubstituted or disubstituted by a substituent selected from a halogen atom, a (C.sub.1 -C.sub.3)alkoxy, a (C.sub.1 -C.sub.3)alkyl and a trifluoromethyl, said substituents being identical or different; a naphthyl; an indolyl;Q and Y have one of the following groups of meanings:a) Q.sub.1 and Y.sub.1 ;b) Q.sub.2 and Y.sub.2 when Am.sup..sym. is a group Am.sub.1.sup..sym., Am.sub.2.sup..sym., Am.sub.4.sup..sym. or Am.sub.5.sup..sym. ;c) Q.sub.3 and Y.sub.3 when Am.sup..sym. is a group Am.sub.1.sup..sym. or Am.sub.2.sup..sym. or a group Am.sub.4.sup..sym. in which Ar.sub.1 is a phenyl and p is two;d) Q.sub.4 and Y.sub.4 when Am.sup..sym. is a group Am.sub.1.sup..sym., Am.sub.3.sup..sym., Am.sub.4.sup..sym. or Am.sub.5.sup..sym. ;Q is hydrogen;Y.sub.1 is hydrogen, a (C.sub.1 -C.sub.4)alkyl, an .omega.-(C.sub.1 -C.sub.4)alkoxy-(C.sub.2 -C.sub.4)alkylene, an .omega.-(C.sub.1 -C.sub.4)alkylcarbonyloxy-(C.sub.2 -C.sub.4)alkylene, an .omega.-benzoyloxy-(C.sub.2 -C.sub.4)alkylene, an .omega.-hydroxy-(C.sub.2 -C.sub.4)alkylene, an .omega.-(C.sub.1 -C.sub.4)alkylthio-(C.sub.2 -C.sub.4)alkylene, an .omega.-(C.sub.1 -C.sub.4)alkylcarbonyl-(C.sub.2 -C.sub.4)alkylene, an .omega.-carboxy-(C.sub.2 -C.sub.4)alkylene, an .omega.-(C.sub.1 -C.sub.4)alkoxycarbonyl-(C.sub.2 -C.sub.4)alkylene, an .omega.-benzyloxy-(C.sub.2 -C.sub.4)alkylene, an .omega.-formyloxy-(C.sub.2 -C.sub.4)alkylene, an .omega.-R.sub.3 NHCOO--(C.sub.2 -C.sub.4)alkylene, an .omega.-R.sub.4 R.sub.5 NCO--(C.sub.2 -C.sub.4)alkylene, an .omega.-R.sub.6 CONR.sub.7 --(C.sub.2 -C.sub.4)alkylene, an .omega.-R.sub.8 OCONR.sub.7 --(C.sub.2 -C.sub.4)alkylene, an .omega.-R.sub.4 R.sub.5 NCONR.sub.7 --(C.sub.2 -C.sub.4)alkylene, an .omega.-R.sub.9 SO.sub.2 NR.sub.7 --(C.sub.2 -C.sub.4)alkylene, an .omega.-cyano-(C.sub.1 -C.sub.3)alkylene;Q.sub.2 and Y.sub.2 together form an ethylene, trimethylene or tetramethylene group;Q.sub.3 and Y.sub.3 together form a group ##STR16##in which n is one, two or three;Q.sub.4 and Y.sub.4 together form a radical selected from:A.sub.1) --O--CH.sub.2 --A.sub.2) --O--CO--A.sub.3) --CH.sub.2 --O--CO--A.sub.4) --O--CH.sub.2 --CO--A.sub.5) --O--CH.sub.2 --CH.sub.2 --A.sub.6) --N(R.sub.10)--CO--A.sub.7) --N(R.sub.10)--CO--CO--A.sub.8) --N(R.sub.10)--CH.sub.2 --CH.sub.2 --T is either a group --CO-- when Q and Y are Q.sub.1 and Y.sub.1, Q.sub.1 and Y.sub.2 or Q.sub.4 and Y.sub.4 when they together form a radical A.sub.1), A.sub.5) or A.sub.8); or a group --CH.sub.2 -- when Q and Y are Q.sub.3 and Y.sub.3 or Q.sub.4 and Y.sub.4 when they together form a radical A.sub.2), A.sub.3), A.sub.4), A.sub.6) or A.sub.7);A is either a direct bond or a methylene group when T is --CO--, or a direct bond when T is --CH.sub.2 --;Z is:a phenyl which is unsubstituted or monosubstituted or polysubstituted by a substituent selected from a halogen atom; a trifluoromethyl; a cyano; a hydroxyl; a nitro; an amino which is unsubstituted or monosubstituted or polysubstituted by a (C.sub.1 -C.sub.4)alkyl; a benzylamino; a carboxyl; a (C.sub.1 -C.sub.10)alkyl; a (C.sub.3 -C.sub.7)cycloalkyl which is unsubstituted or monosubstituted or polysubstituted by a methyl; a (C.sub.1 -C.sub.10)alkoxy; a (C.sub.3 -C.sub.7)cycloalkoxy which is unsubstituted or monosubstituted or polysubstituted by a methyl; a mercapto; a (C.sub.1 -C.sub.10)alkylthio; a (C.sub.1 -C.sub.6)alkylcarbonyloxy; a (C.sub.1 -C.sub.6)alkylcarbonylamino; a benzoylamino; a (C.sub.1 -C.sub.4)alkoxycarbonyl; a (C.sub.3 -C.sub.7)cycloalkylcarbonyl; a carbamoyl which is unsubstituted or monosubstituted or disubstituted by a (C.sub.1 -C.sub.4)alkyl; a ureido which is unsubstituted or monosubstituted or disubstituted in the 3-position by a (C.sub.1 -C.sub.4)alkyl or a (C.sub.3 -C.sub.7)cycloalkyl; and a (pyrrolidin-1-yl)carbonylamino, said substituents being identical or different;a naphthyl which is unsubstituted or monosubstituted or polysubstituted by a halogen, a trifluoromethyl, a (C.sub.1 -C.sub.4)alkyl, a hydroxyl or a (C.sub.1 -C.sub.4)alkoxy;a pyridyl; a thienyl; an indolyl; a quinolyl; a benzothienyl; an imidazolyl;R.sub.3 is a (C.sub.1 -C.sub.7)alkyl or a phenyl;R.sub.4 and R.sub.5 are each independently a hydrogen or a (C.sub.1 -C.sub.7)alkyl; R, can also be a (C.sub.3 -C.sub.7)cycloalkyl, a (C.sub.3 -C.sub.7)cycloalkylmethyl, a phenyl or a benzyl; or R.sub.4 and R.sub.5, together with the nitrogen atom to which they are bonded, form a heterocycle selected from azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, perhydroazepine and piperazine which is unsubstituted or substituted in the 4-position by a (C.sub.1 -C.sub.4)alkyl;R.sub.6 is a hydrogen, a (C.sub.1 -C.sub.7)alkyl, a vinyl, a phenyl, a benzyl, a pyridyl or a (C.sub.3 -C.sub.7)cycloalkyl which is unsubstituted or substituted by one or more methyls;R.sub.7 is a hydrogen or a (C.sub.1 -C.sub.7)alkyl;R.sub.8 is a (C.sub.1 -C.sub.7)alkyl or a phenyl;R.sub.9 is a (C.sub.1 -C.sub.7)alkyl; an amino which is unsubstituted or substituted by one or two (C.sub.1 -C.sub.7)alkyls; a phenyl which is unsubstituted or monosubstituted or polysubstituted by a substituent selected from a halogen atom, a (C.sub.1 -C.sub.7)alkyl, a methfluoromethyl, a hydroxyl, a (C.sub.1 -C.sub.7)alkoxy, a carboxyl, a (C.sub.1 -C.sub.7)alkoxycarbonyl, a (C.sub.1 -C.sub.7)alkylcarbonyloxy, a cyano, a nitro and an amino which is unsubstituted or substituted by one or two (C.sub.1 -C.sub.7)alkyls, said substituents being identical or different;R.sub.10 is hydrogen or a (C.sub.1 -C.sub.4)alkyl, or one of its salts with mineral or organic acids, if appropriate, and one of their solvates, if appropriate, formulated by wet granulation, containing the following as percentages of the total weight of the formulation:active principle 0.5 to 50% binder 1 to 10% disintegrating agent 0 to 10% antiadhesive 0 to 5% lubricant 0.2 to 5% flow promoter 0 to 15% polysorbate 80 4 to 20% color 0 to 2% flavoring 0 to 2% diluent in sufficient amount (QS) for 100%.