IL38705A - 6-phenyl-4,5-dihydro-3(2h)-pyridazinone derivatives,their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

1383906 6-Phenyl-4,5-dihydro-3(2H)-pyridazinones BDH PHARMACEUTICALS Ltd 18 Feb 1972 [22 Feb 1971] 5082/71 Heading C2C Novel 6-phenyl-4,5-dihydro-3(2H)-pyridazinones of the general formula wherein X is a fluorine or chlorine atom or a straight or branched chain alkyl or alkoxy, hydroxymethyl, cycloalkyl, cycloalkoxy, aryloxy, hydroxyl, amino, non-heterocyclic substituted amino, piperidino, morpholino, pyrrolidino, 1,2,3,6 - tetrahydropyridino or 4-[3- azabicyclo(3,2,2)nonyl] group or a group of formula wherein R is a hydrogen atom or a C 1-5 alkyl, optionally substituted aryl, aralkyl, cinnamyl, ethoxycarbonyl or optionally substituted acyl group, and n is 1-5; except that when n is 1, X is not a C 1-3 alkyl, C 1-2 alkoxy or optionally acylated amino group or a 41-chlorine atom; when n is 2, the X substituents are not both methyl groups in the 2 and 5<SP>1</SP>, 3<SP>1</SP> and 4<SP>1</SP> or 2<SP>1</SP> and 4<SP>1</SP> positions or methoxy groups in the 2<SP>1</SP>- and 5<SP>1</SP>-positions or chlorine atoms in the 2<SP>1</SP>- and 4<SP>1</SP>- or 3<SP>1</SP>- and 4<SP>1</SP>-positions; and when n is 3, all three X substituents are not methoxy groups; are prepared (a) by reaction of a #- benzoyl-propionic acid of the general formula with hydrazine hydrate or (b) when X is an alkoxy group, by reaction of the corresponding compound in which X is a hydroxyl group with an alkyl halide in the presence of an acid binding agent. #-Benzoyl-propionic acids of the second general formula above are prepared (a) by hydrolysis of a corresponding alkyl ester (an ethoxycarbonyl group R may simultaneously be removed and, when X is a hydroxymethyl group, the starting material may be the corresponding chloromethyl derivative); (b) by reaction of a substituted benzene with succinic anhydride in the presence of aluminium chloride; (c) when X is an amino group, by reduction of the corresponding nitro compound; (d) when X is a chlorine atom, by diazotization of the corresponding amino compound, followed by treatment with an aqueous solution containing sodium chloride, hydrated copper sulphate, sodium metabisulphite and sodium hydroxide; (e) when X is an acetamido group, by acetylation of the corresponding amino compound, (f) when X is a hydroxyl group, by treatment of a succinic acid monophenyl ester with aluminium chloride, and (g) when X is an alkoxy group, by alkylation of the corresponding hydroxy compound. The #-benzoyl-propionic acid alkyl esters are prepared (a) when X is a basic group, by reaction of the corresponding compound in which X is a fluorine atom with XH; (b) when X is as alkoxy group, by alkylation of the corresponding hydroxy compound; (c) when X is a fluorine atom or hydroxy group, by esterification of the corresponding acid; and (d) when X is a chloromethyl group, by treatment of the corresponding compound in which X is a hydrogen atom with paraformaldehyde, anhydrous zinc chloride and hydrogen chloride. Pharmaceutical compositions having antihypertensive activity comprise, as active ingredient, a 6-phenyl-4,5-dihydro-3(2H)-pyridazinone of the first general formula above, in association with a pharmaceutically acceptable carrier or diluent. [GB1383906A]

Claims (1)

1. CLAIMS Compounds of the general formu in which X represents a straight or branched chain alkyl group containing up to 6 carbon atoms or alkoxy group containing, from 1 to 12 carbon atoms, a hydroxymethyl group, a cycloalkyl group \ containing 4 to 7 carbon atoms? a cycloalkoxy group containing 4 to 7 carbon atoms,, a "phenoxy group, a hydroxy1 group, a fluorine atom, a chlorine atom, a piperidirto group, a morpholino group, a pyrrolidino group, a 1 , 2 , 3 , 6-tetrahydropyridino group, a 4- [3-azabicyclo (3,2 ,2) -nonyl] group, or a 4- (piperaz^n-l- yl) or 4- (4-substituted-piperazin-l-yl) group of the formula in which R=H, lower alkyl of 1-5 carbon atoms, phenyl optionally substituted with C1_(- alkyl or Οχ_6 alkoxy, phenyl-alkyl the alkyl position of which contains 1 to 5 carbon atoms, ethoxy-carbonyl or benzoyl, and n is 1 or 2 except that when n is 1, X is not an alkyl group of .1 to 3 carbon atoms or an alkoxy group of 1 or 2 carbon atoms or a chlorine atom in the 4' -position, ( and when n is 2, the groups X cannot both be methyl or both be methoxy in the 2' and 5' positions, nor can X be a chlorine atom in both the 2' and 4' positions or the 3' and 4' 38705/2 (b) for the production of those compounds in which X represents an alkoxy group containing from 1 to 12 carbon atoms, reacting a hydroxyphenyl pyridazinone of the formula: 1 38705/2 which the acid II specified in (a) is a meta-acid and this is prepared by the nitration of 3-kenzoylpropionic acid, reduction of the resulting m-nitro acid and diazotization of the resulting m-amino acid to yield the m-chloro or m-hydroxy ND:ed