Patent ES-356976-A1 (ES)
Title: 1h - imidazo(4,5-b)pyrazin - 2 - one and processes for their preparation
IPC: A61K31/535
Filed: 1968-08-06
Abstract: Novel compounds I in which R1 and R2 are H, C 2-6 alkanoyl, C 3-7 cycloalkyl, C 3-5 alkenyl, (C 1-3 alkoxy) carbonyl or a C 1-5 alkyl radical unsubstituted or substituted by one or more OH, C 1-3 alkoxy, a heterocyclic group having 5 or 6 ring atoms with 1 or more O and/or N heteroatoms, (C 1-3 alkoxy) carbonyl, hydrazinocarbonyl, phenyl, amino, C 1-5 alkylamino or di(C 1-5 -alkyl) amino R 3 is H, C 3-5 alkenyl, C 3-5 alkynyl, C 3-7 cycloalkyl, phenyl, halogenated phenyl, (C 1-3 alkyl) phenyl, (C 1-3 alkoxy) phenyl, C 1-4 alkoxy, amidino or a C 1-6 alkyl radical unsubstituted or substituted by one or more OH, C 1-3 alkoxy, C 3-6 cycloalkyl, halo, a heterocyclic group as defined above, phenyl, halophenyl, (C 1-3 alkyl) phenyl, (C 1-3 alkoxy) phenyl, or -NR6R7 R4 is H or an aliphatic hydrocarbon radical or R3 and R4 together with the adjacent N form a heterocyclic ring which may also contain an O atom, an N 2 group or a bis[di(C 1-5 -alkyl) amino] methylene group R6 is H or C 1-5 alkyl R7 is H, or C 1-5 alkyl or R6 and R7 together with the adjacent N form a heterocyclic group optionally containing an O atom and R5 is H, halo, C 1-6 alkyl, phenyl, halophenyl, (C 1-3 alkyl) phenyl or (C 1-3 alkoxy) phenyl are prepared (a) by diazotization of a compound II wherein R10 is H, C 1-5 alkyl, C 3-7 cycloalkyl, C 1-5 hydroxyalkyl, (C 1-3 alkoxy)-C 1-5 alkyl, C 3-5 alkenyl, or di(C 1-5 alkyl) amino-C 1-5 alkyl, with an alkali metal nitrite in acid medium, followed by heating the resultant azide in alcoholic solution to give a compound I in which R1 is R10 and R2 is H (b) by reaction of a compound I in which R1 and R2 are H with a C 1-5 alkyl iodide or bromide, a di (C 1-5 alkyl) sulphate, a C 1-3 alkyl C 2-6 -[alpha]-bromoalkanoate, a C 1-3 alkyl chloroformate, a C 2-6 alkanoic acid anhydride, a C 3-7 cycloalkyl iodide or bromide, a di (C 1-5 alkyl) amine and formaldehyde or morpholine or piperidine and formaldehyde to give a compound I in which R1 and R2 are both the same and are C 1-5 alkyl, (C 1-3 alkoxy) carbonyl-(C 1-5 alkyl), (C 1-3 alkoxy) carbonyl, C 2-6 alkanoyl C 3-7 cycloalkyl, di (C 1-5 alkyl) amino methyl, morpholinomethyl or piperidinomethyl or (c) by reaction of a compound I in which R1 is R10 and R2 is H with a reagent selected from those listed under (b) to give an appropriately substituted compound I. Compounds of Formula III in which R is alkyl are prepared by reaction of R 3 NH(R 4 ) with an appropriate 5,6-dichloro compound. Compounds of Formula IV are prepared by reaction of R1NH 2 with the appropriate 2-bromo compound which in turn is prepared from the 2-amino compound by reaction with sodium nitrite, bromine and hydrobromic acid. Compounds of Formula II are prepared by reaction of the appropriate compounds III and IV with hydrazine. Pharmaceutical compositions useful as antihypertensive agents comprise a compound I together with a suitable carrier or diluent and are administered orally, topically or parenterally. Compounds I also exhibit diuretic, saluretic, bronchodilator, gastric-acid-inhibiting and cardiac stimulating activity.