GB884151A - New pyrazolo-pyrimidines substituted in the pyrazole nucleus, and process for their manufacture - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:0884151/IV (b)/1> or <FORM:0884151/IV (b)/2> and acid addition salts thereof, wherein R2 is a saturated hydrocarbon radical of up to 6 carbon atoms, e.g. alkyl and R3 is an amino group optionally substituted by one or two aliphatic radicals of 1-6 carbon atoms or a heterocyclic amino group. The compounds are prepared by reacting a 2-R3-4-halo-5-cyano-pyrimidine with a hydrazine R2NH.NH2. The products are used pharmaceutically, suitably in the form of acid addition salts (see Group VI). Examples describe the preparation of 1- or 2-isopropyl-6-dimethylamino-;1-methyl-6-morpholino- and 1- and 2-pentyl-(21)-6-dimethylamino-, pyrazolo-[3 : 4-d]-pyrimidine. 2 - substituted - 4 - halo - 5 - cyano - pyrimidines used as starting materials, e.g. 2-dimethylamino-4-chloro-5-cyano-pyrimidine and 2-morpholino-4-chloro-5-cyanopyrimidine are made by reacting an a -ethoxymethylene-a -cyanacetic ester with an S-alkyl-isothiourea to give 2-alkyl-mercapto (e.g. methylmercapto) - 4 - hydroxy - 5 - cyano - pyrimidine which is reacted with an amine such as dimethylamine or morpholine to give a 2-substituted-4-hydroxy-5-cyano-pyrimidine which is treated with phosphorus oxychloride. S-methylisothioureido-methylene cyanoacetic ester is obtained as the initial product of the condensation of a -ethoxymethylene-a -cyanoacetic ester and S-methylisothiourea.ALSO:Pharmaceutical preparations having tumour inhibiting, diuretic, coronary-dilating, central nervous system inhibiting and anti-rheumatic effects and acting as anti-metabolites of purine comprise pyrazolo-pyrimidine compounds of the formula <FORM:0884151/VI/1> or <FORM:0884151/VI/2> or acid addition salts thereof, wherein R2 is a saturated hydrocarbon radical of up to 6 carbon atoms, e.g. alkyl and R3 is an amino group optionally substituted by one or two aliphatic radicals of 1-6 carbon atoms or a heterocyclic amino group (see Group IV (b) in admixture or association with a pharmaceutical carrier. The preparations suitably take the form of solutions, suspensions, emulsions, tablets or dragees and may contain auxiliary substances such as stabilizing, wetting or emulsifying agents. Specified salts are hydrohalides, sulphates, phosphates, nitrates, perchlorates, formates, acetates, propionates, oxalates, succinates, glycollates, lactates, malates, tartrates, citrates, ascorbates, mono- and di-hydroxymaleates, pyruvates, phenylacetates, benzoates, p-aminobenzoates, anthranilates, p-hydroxybenzoates, salicylates, p - aminosalicylates, methane-, ethane -, ethylene -, hydroxyethane -, toluene-and naphthalene-sulphonates, sulphanilates and salts with methionine, lysine, tryptophane and arginine.