DK89685A - ALLOPURINOL DERIVATIVES - Google Patents

Abstract

Compounds of the general formula Ia or Ib <IMAGE> where R1 is a group of the general formula II <IMAGE> where R3 is alkyl; phenyl; phenyl which is substituted by halogen, lower alkyl, hydroxyl, lower alkoxy, acetoxy or phenoxy; phenyl-lower alkyl, where the phenyl group can be substituted by halogen, lower alkyl, hydroxyl, lower alkoxy, acetoxy or phenoxy; or phenyl-lower alkenyl, where the phenyl group can be substituted by halogen, lower alkyl, hydroxyl, lower alkoxy, acetoxy or phenoxy; or R3 is an aromatic 5- or 6-membered heterocyclic ring which contains 1 or 2 hetero atoms selected from the class consisting of nitrogen, oxygen and sulphur; and A is a single bond or a group of the general formula IIa <IMAGE> where the carbon atom is bonded to the nitrogen atom of the original ring system and where R6 and R7 are identical or different and are each hydrogen or have the same meaning as R3, as defined above; or R1 is a group of the general formula III <IMAGE> where R8 and R9 are identical or different and each denote hydrogen or have the same meaning as R3, as defined above; or R8 and R9, together with the adjacent nitrogen atom, form a 5- or 6-membered heterocyclic ring which, over and above the nitrogen atom, can contain one or two additional hetero atoms selected from the class consisting of nitrogen, oxygen and sulphur; Y is a single bond or a group of the general formula IIIa <IMAGE> where n is an integer from 1 to 5; and A, R6 and R7 are as defined above; or R1 is a group of the general formula IV <IMAGE> where A is as defined above, and R3' has the same meaning as R3 defined above, with the proviso that R3' is not ethyl when A is a bond; or R1 is a group of the general formula VI <IMAGE> where R10 is a mono- or poly-halogenated lower alkyl group, and A is as defined above; or R1 is a group of the general formula VII <IMAGE> where n and A are as defined above, and R13 is hydroxyl or a group of the general formula -NR8R9, where R8 and R9 are as defined above; or R1 is a group of the general formula IX <IMAGE> where R6 and R7 are as defined above; R2 is any of the groups of the general formulae II, III, IV, VI and VII as defined above, with the proviso that A is only the group of the general formula IIa as defined above; and R5 is hydrogen or has the same meaning as R2 as defined above, and salts thereof. The compounds of the general formulae Ia and Ib are prodrugs of allopurinol and have, inter alia, a much higher solubility in water and/or a higher lipophilicity than allopurinol, which makes these compounds extremely well-suited for oral, parenteral and rectal administration to a homeothermic animal such as man. Following administration, these compounds will be converted into allopurinol.