Patent EA-004806-B1 (EA)
Title: Il-5 inhibiting 6-azauracil derivatives
Inventor: FREYNE EDDY JEAN EDGARD
IPC: C07D253/075
Filed: 1999-12-16
Abstract: 1. A compound of formula a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein: p represents an integer being 0, 1 or 2; q represents an integer being 1; X represents S or R<1> represents hydrogen; R<2> represents pyridyl, substituted with -C(=O)-Z-R<14>, or C1-6alkyl, substituted with one or two substituents selected from NR<7>R<8> and Het<3>; each R<4> independently represents halogen; each R<5> independently represents halogen each R<7> and R<8> are independently selected from hydrogen, C1-4alkyl, -C(=O)-Z-R<14> and Het<3>; each Z independently represents O or S, each R<14> independently represents hydrogen and C1-20alkyl; or R<14> represents a radical of formula: s is zero to 4; Het<3> represents a monocyclic heterocycle selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl and tetrahydropyranyl; wherein said monocyclic heterocycles each independently may optionally be substituted with, where possible, one, two. three or four substituents each independently selected from hydroxy, C1-4alkyl, C1-4alkyloxy,-C (=O)-Z-R<14>, C1-4alkylcarbonyl. 2. A pharmaceutical composition for treating eosinophil-dependent inflammatory diseases comprising a compound according to claim 1 as an active ingredient and pharmaceutically acceptable carrier or excipient. 3. Use a compound according to claim 1 as a medicament for treating eosinophil-dependent inflammatory diseases. 4. Use of a compound according to claim 1 in the manufacture of a medicament for treating bronchial asthma. 5. A process for preparing a compound according to claim 1, characterised by reacting an intermediate of formula (II) wherein W<1> is a suitable leaving group with an appropriate reagent of formula (III) optionally in a reaction-inert solvent and in the presence of a base: wherein R<1>, R<2> R<4>, X and q are as defined in claim 1, and D represents wherein R<5> and p are defined as in claim 1, and if desired, converting compounds of formula (I) into each other following art-known transformations, and further, if desired, converting the compounds of formula (I), into a therapeutically active non-toxic acid addition salt by treatment with an acid, or into a therapeutically active non-toxic base addition salt by treatment with a base, or conversely, converting the acid addition salt form into the free base by treatment with alkali, or converting the base addition salt into the free acid by treatment with acid; and also, if desired, preparing stereochemically isomeric forms or N-oxide forms thereof. 6. A process for preparing a compound according to claim 1, characterised by eliminating the group E of a triazinedio of formula (V) wherein R<1>, R<2>, R<4>, R<5>, X and q are as defined in claim 1, and if desired, converting compounds of formula(I) into each other following art-known transformations, and further, if desired, converting the compounds of formula (I), into a therapeutically active non-toxic acid addition salt by treatment with an acid, or into a therapeutically active non-toxic base addition salt by treatment with a base, or conversely, converting the acid addition salt form into the free base by treatment with alkali, or converting the base addition salt into the free acid by treatment with acid; and also, if desired, preparing stereochemically isomeric forms or N-oxide forms thereof. 7. A process for preparing a compound according to claim 1, characterised by reacting an intermediate of formula (XII) wherein W<4> is a suitable leaving group with an intermediate of formula (III) optionally in the presence of a suitable base; thus obtaining a compounds of formula (I-b): wherein R<2>, R<4>, X and q are as defined in claim 1 and D is defined as in claim 5 and if desired, converting compounds of formula(I) into each other following art-known transformations, and further, if desired, converting the compounds of formula (I), into a therapeutically active non-toxic acid addition salt by treatment with an acid, or into a therapeutically active non-toxic base addition salt by treatment with a base, or conversely, converting the acid addition salt form into the free base by treatment with alkali, or converting the base addition salt into the free acid by treatment with acid; and also, if desired, preparing stereochemically isomeric forms or N-oxide forms thereof. 8. A process of marking a receptor comprising the steps of: a) radiolabelling a compound as defined in claim 1; b) administering said radiolabelled compound to biological material, c) detecting the emissions from the radiolabelled compound. 9. A process of imaging an organ, characterised by administering a sufficient amount of a radiolabelled compound of formula (I) in an appropriate composition, and detecting the emissions from the radioactive compound.