Patent ID: 6448244
Filing Date: 2002-09-10
Classification: A61P,C07D

Abstract:
A compound of formula a N-oxide form, a pharmaceutically acceptable addition salt or a stereochemically isomeric form thereof, whereinL represents a radical of formula â€ƒwherein each Alk independently represents C1-6alkanediyl optionally substituted with hydroxy or C1-4akyloxy provided that when L represents formula (a) then Alk represents C3-6 alkanediyl optionally substituted with hydroxy or C1-4 alkyloxy; each n independently is 1, 2 or 3; Y represents O, S or NR2; each R1 independently represents aryl, Het1, or C1-6alkyl optionally substituted with one, two or three substituents each independently selected from halo, hydroxy, mercapto, C1-4alkyloxy, C1-4alkylthio, aryloxy, arylthio, arylC1-4alkyloxy, arylC1-4alkylthio, cyano, amino, mono- or di(C1-4alkyl)amino, mono- or di(aryl)amino, mono- or di(arylC1-4alkyl)amino, C1-4alkyloxycarbonylamino, benzyloxycarbonylamino, aminocarbonyl, carboxyl, C1-4alkyloxycarbonyl, guanidinyl, aryl or Het2; each R2 independently represents hydrogen; or in case R1 and R2 are attached to the same nitrogen atom, they may be taken together to form a heterocyclic radical selected from morpholinyl, pyrrolidinyl, piperidinyl, homopiperidinyl or piperazinyl; said heterocyclic radical may optionally be substituted with C1-4alkyl, aryl, Het2, arylC1-4alkyl, Het2C1-4alkyl, hydroxyC1-4alkyl, amino, mono- or di(C1-4alkyl)amino, aminoC1-4alkyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, carboxyl, aminocarbonyl, C1-4alkyloxycarbonyl, C1-4alkyloxycarbonylamino or mono- or di(C1-4alkyl)aminocarbonyl; or they may be taken together to form an azido radical; each R3 independently represents hydrogen, hydroxy or C1-4alkyloxy; aryl represents phenyl, naphthalenyl, 1,2,3,4-tetrahydro-naphthalenyl, indenyl or indanyl; each of said aryl groups may optionally be substituted with one or more substituents selected from halo, C1-4alkyl, hydroxy, C1-4alkyloxy, nitro, amino, trifluoromethyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, aminoC1-4alkyl, mono- or di(C1-4alkyl)aminoC1-4alkyl; Het1 represents a monocyclic or bicyclic heterocyclic radical; said monocyclic heterocyclic radical being selected from the group pyridinyl, piperidinyl, homopiperidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, triazolyl, pyranyl, tetrahydropyranyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, thiazolyl, thiazolidinyl, isothiazolyl, oxazolyl, oxazolidinyl, isoxazolyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, furanyl, tetrahydrofuranyl, thienyl, thiolanyl, dioxolanyl; said bicyclic heterocyclic radical being selected from the group quinolinyl, 1,2,3,4-tetrahydro-quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, phtalazinyl, cinnolinyl, chromanyl, thiochromanyl, 2H-chromenyl, 1,4-benzodioxanyl, indolyl, isoindolyl, indolinyl, indazolyl, purinyl, pyrrolopyridinyl, furanopyridinyl, thienopyridinyl, benzothiazolyl, benzoxazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, benzofuranyl, benzothienyl; whereby each of said mono- or bicyclic heterocycle may optionally be substituted with one or where possible more substituents selected from halo, C1-4alkyl, hydroxy, C1-4alkyloxy, nitro, amino, trifluoromethyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, aminoC1-4alkyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, aryl or arylC1-4alkyl; Het2 is the same as Het1 and may also be a monocyclic heterocycle selected from piperazinyl, homopiperazinyl, 1,4-dioxanyl, morpholinyl, thiomorpholinyl; whereby each of said monocyclic heterocycle may optionally be substituted with one or where possible more substituents selected from halo, C1-4alkyl, hydroxy, C1-4alkyloxy, nitro, amino, trifluoromethyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, aminoC1-4alkyl, mono- or di-(C1-4alkyl)aminoC1-4alkyl, aryl or arylC1-4alkyl; R6 represents hydrogen or C1-4alkyl; R7 represents hydrogen or C1-4alkyl; or R6 and R7 taken together form a bivalent radical of formula â€”R6â€”R7â€” wherein â€”R6â€”R7â€” is: â€”N&boxH;CHâ€”â€ƒâ€ƒ(i), â€”CH&boxH;Nâ€”â€ƒâ€ƒ(ii), â€”CH&boxH;CHâ€”â€ƒâ€ƒ(iii), â€”CH2â€”CH2â€ƒâ€ƒ(iv), wherein one hydrogen atom in the radicals (i) and (ii) may be replaced with a C1-4alkyl radical and one or more hydrogen atoms in radicals (iii) and (iv) may be replaced by a C1-4alkyl radical; D represents a radical of formula â€ƒwherein X is N or CH; R4 is hydrogen or halo; R5 is halo.