Patent GB-1039963-A (GB)
Title: Improvements relating to pyrazole derivatives
IPC: C08F2/38
Filed: 1964-05-29
Abstract: The invention comprises compounds of formula <FORM:1039963/C2/1> wherein the ring contains two double bonds and the -CXNR1R2 group is attached to one of the ring-nitrogen atoms, X is oxygen or sulphur, R1 is a methyl group and R2 is a C1- 6 alkyl, C3- 6 alken-2-yl, C2- 6 alkoxyalkyl, C2- 6 hydroxyalkyl, dimethylamino, or C3- 7 dimethyl- or diethylaminoalkyl, wherein the alkyl moiety has 1 to 4 carbon atoms, group, or the group -NR1R2 is a morpholino, pyrrolidino, 3,4-dehydropiperidino or 3-azabicyclo[3,2,2]nonyl group, or a group <FORM:1039963/C2/2> wherein Y1 is a hydrogen atom or a methyl group, Y2 is a hydrogen atom or a methyl, ethyl, C2- 6 hydroxyalkyl or C2- 5 alkoxycarbonyl group, and Y3 is a hydrogen atom or a C1- 6 alkyl, C2- 6 hydroxyalkyl, trifluoromethyl, C2- 5 alkoxycarbonyl, C3- 7 dimethyl- or diethylaminoalkyl, wherein the alkyl moiety has 1 to 4 carbon atoms, C7- 9 aralkyl or b -pyrrolidinoethyl group, R3 is a hydrogen atom or a C1- 3 acyl group and R4 is a hydrogen, fluorine, chlorine or bromine atom or a C1- 3 alkyl or trifluoromethyl group, and their preparation by (a) reaction of a pyrazole-1-carbonyl or -thiocarbonyl chloride, or a 1-alkoxycarbonyl or 1-alkoxythiocarbonyl pyrazole, with an amine, (b) reaction of a pyrazole with an amine carbonyl or thiocarbonyl chloride or (c) reaction of a 3(5)-p-dimethylaminobenzalamino-pyrazole with 2,4-dinitrophenylhydrazone.  3(5) - p - Dimethylaminobenzalamino - 1 - dimethylcarbamyl-pyrazole is prepared by reaction of 3-aminopyrazole and benzaldehyde to form 3 - (p - dimethylaminobenzalamino) - pyrazole, and reacting this with sodium hydride and 1-dimethylcarbamyl-pyrazole.  3 - Acetamido - 4 - bromo - pyrazole is prepared by bromination.  3-Acylamino-pyrazoles are prepared by acylation.ALSO:Pharmaceutical compositions having analgesic, anti-inflammatory and central nervous system activity comprise, in combination with a carrier, a compound of formula <FORM:1039963/A5-A6/1> wherein X is oxygen or sulphur, the ring contains two double bonds and the group -CXNR1R2 is attached to one of the nitrogen atoms, R1 is a methyl group and R2 is a C1-6 alkyl, (3-6 alken-2-yl, C2-6 alkoxyalkyl, C2-6 hydroxyalkyl, dimethylamino, or dimethyl-or diethyl-aminoalkyl wherein the alkyl moiety has 1 to 4 carbon atoms and the whole group 3 to 7 carbon atoms, or the group -NR, R2 is a morpholino, pyrolidino, 3, 4-dehydropiperidino or 3 oza-binyreo-[3, 2, 2] nonyl group, or 4 group <FORM:1039963/A5-A6/2> wherein Y1 is a hydrogen atom or a methyl group Y2 is a hydrogen atom or a methyl, ethyl, C2-6 hydroxyalkyl or C2-5 alkoxycarbonyl group, and Y3 is a hydrogen atom or a C1-6 alkyl, C2-6 hydroxyalkyl, trifluoromethyl, C2-5 alkoxycarbonyl, C3-7 dimethyl-or diethyl-aminoalkyl wherein the alkyl moiety has 1 to 4 carbon atoms, b -pyrolidinoethyl or C7-9 aralkyl group, R3 is a hydrogen atom or a C1-3 aryl group, and R4 is a hydrogen, fluorine, chlorine or bromine atom or a C1-3 alkyl or trifluoromethyl group.  The compositions may be in forms suitable for oral or parenteral administration with carriers such as water, saline, aqueous sugars, alcohols, oils, including cod-liver oil, or gums, and may contain other pharmaceutically active substances, for example vitamins, analgesics, tranquillisers, antibiotics and anti tussive agents.  The forms taken may be hard or soft capsules, delayed release oral forms, powders, tablets, and oral or injectable solutions or suspensions, e.g. an injectable saline solution, a tablet with gelatin, talc, and a mannitol filler, and a capsule with a corn starch filler.