Patent ID: 6469001
Filing Date: 2002-10-22
Classification: A61P,C07D

Abstract:
A compound of formula a N-oxide, a pharmaceutically acceptable addition salt or a stereochemically isomeric forms thereof, wherein:p represents an integer being 0, 1, 2 or 3; q represents an integer being 0, 1, 2, 3, 4 or 5; â€”Aâ€”Bâ€” represents â€”(CH2)râ€”, â€”(CH2)tâ€”Oâ€”, â€”(CH2)tâ€”S(&boxH;O)uâ€” or â€”(CH2)tâ€”NR3â€”; r represents 2, 3 or 4; each t independently represents 1, 2 or 3; u represents 0, 1 or 2; X1 represents O, S, NR3 or a direct bond; each R1 independently represents C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or C1-4alkyl substituted with Het3, R6 or NR7R8; R2 represents aryl, Het1, C3-7cycloalkyl, cyano, C1-6alkyl, â€”C(&boxH;Q)â€”X2â€”R15 or C1-6alkyl substituted with one or two substituents selected from hydroxy, cyano, amino, mono-or di(C1-4alkyl)amino, C1-6alkyloxy, C1-6alkylsulfonyloxy, C1-6alkyloxycarbonyl, C3-7cycloalkyl, aryl, aryloxy, arylthio, Het1, Het1oxy, Het1thio and â€”C(&boxH;Q)â€”X2â€”R15; R3 represents hydrogen or C1-4alkyl; each R4 independently represents C1-6alkyl, halo, polyhaloC1-6alkyl, hydroxy, mercapto, C1-6alkyloxy, C1-6alkylthio, C1-6alkylcarbonyloxy, aryl, cyano, nitro, Het3, R6, NR7R8 or C1-4alkyl substituted with Het3, R6 or NR7R8; each R15 independently represents hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl or C1-6alkyl substituted with aryl, halo, hydroxy or Het1; where X2 is a direct bond, R15 may also be halo or Het1; where X2 is NR5, R15 may also be hydroxy; where X2 is C(&boxH;O)â€”NHâ€”NH or NHâ€”NHâ€”C(&boxH;O), R15 may be replaced by R11; R5 represents hydrogen, C1-6alkyl, C1-6alkyloxy or arylC1-6alkyl; each Q independently represents O, S or NR3; each X2 independently represents O, S, NR5, C(&boxH;O)â€”NHâ€”NH, NHâ€”NHâ€”C(&boxH;O) or a direct bond; each R6 independently represents C1-6alkylsulfonyl, aminosulfonyl, mono- or diâ€”(C1-4alkyl)aminosulfonyl, mono- or di(benzyl)aminosulfonyl, polyhaloC1-6alkylsulfonyl, C1-6alkylsulfinyl, phenylC1-4alkylsulfonyl, piperazinylsulfonyl, aminopiperidinylsulfonyl, piperidinylaminosulfonyl, Nâ€”C1-4alkyl-N-piperidinylaminosulfonyl or mono-or di(C1-4alkyl)aminoC1-4alkylsulfonyl; each R7 and each R8 are independently selected from hydrogen, C1-4alky), hydroxy-C1-4alkyl, dihydroxyC1-4alkyl, aryl, arylC1-4alkyl, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyl, aminocarbonyl, arylcarbonyl, Het3carbonyl, C1-4alkylcarbonyloxy-C1-4alkylcarbonyl, hydroxyC1-4alkylcarbonyl, C1-4alkyloxycarbonylcarbonyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, arylaminocarbonyl, arylaminothiocarbonyl, Het3aminocarbonyl, Het3aminothiocarbonyl, C3-7cycloalkyl, pyridinylC1-4alkyl, C1-4alkanediyl-C(&boxH;O)â€”Oâ€”R14, â€”C(&boxH;O)â€”Oâ€”R14, â€”Yâ€”C1-4alkanediyl-C(&boxH;O)â€”Oâ€”R14, Het3 and R6; Y represents O, S, NR3, or S(O)2; R9 and R10 are each independently selected from hydrogen, C1-4alkyl, hydroxyC1-4alkyl, dihydroxyC1-4alkyl, phenyl, phenyC1-4alkyl, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyl, aminocarbonyl, phenylcarbonyl, Het3carbonyl, C1-4alkylcarbonyloxyC1-4alkylcarbonyl, hydroxyC1-4alkylcarbonyl, C1-4alkyloxycarbonylcarbonyl, mono- or di(C1-4alkyl)aminoC1-4alkyl, phenylaminocarbonyl, phenylaminothiocarbonyl, Het3aminocarbonyl, Het3aminothiocarbonyl, C3-7cycloalkyl, pyridinylC1-4 alkyl, C1-4alkanediylâ€”C(&boxH;O)â€”Oâ€”R14, â€”C(&boxH;O)â€”Oâ€”R14, â€”Yâ€”C1-4alkanediylâ€”C(&boxH;O)â€”Oâ€”R14, Het3 R6; each R11 independently being selected from hydroxy, mercapto, cyano, nitro, halo, trihalomethyl, C1-4alkyloxy, formyl, trihaloC1-4alkylsulfonyloxy, R6, NR7R8, C(&boxH;O)NR7R8, â€”C(&boxH;O)â€”Oâ€”R 14, â€”Yâ€”C1-4alkanediylâ€”C(&boxH;O)â€”Oâ€”R14, aryl, aryloxy, arylcarbonyl, C3-7cycloalkyl, C3-7cycloalkyloxy, phthalimide-2-yl, Het3, Het4 and C(&boxH;O)Het3; R12 and R13 are each independently selected from hydrogen, C1-4alkyl, hydroxyC1-4alkyl, dihydroxycC1-4alkyl, phenyl, phenylC1-4alkyl, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyl, phenylcarbonyl, C1-4alkylcarbonyloxyC1-4alkylcarbonyl, hydroxyC1-4alkylcarbonyl, C1-4alkyloxycarbonylcarbonyl, mono- or di (C1-4alkyl)aminoC1-4alkyl, phenylamino-carbonyl, phenylaminothiocarbonyl, C3-7cycloalkyl, pyridinylC1-4alkyl, C1-4alkanediyl-C(&boxH;O)â€”Oâ€”R14, â€”C(&boxH;O)â€”Oâ€”R14, â€”Yâ€”C1-4alkanediylâ€”C(&boxH;O)â€”Oâ€”R14 and R6; each R14 independently represents hydrogen, C1-4alkyl, C3-7cycloalkyl, aminocarbonylmethylene, mono-or di(C1-4alkyl)aminocarbonylmethylene, mono-or di(C3-7cycloalkyl)aminocarbonylmethylene, azetidin-1-ylcarbonylmethylene, pyrrolidin-1-ylcarbonylmethylene, piperidin-1-ylcarbonylmethylene or homopiperidin-1-ylcarbonylmethylene; aryl represents phenyl optionally substituted with one, two or three substituents each independently selected from nitro, azido, cyano, halo, hydroxy, C1-4alkyl, C3-7cyclo-alkyl, C1-4alkyloxy, formyl, polyhaloC1-4alkyl, NR9R10, C(&boxH;O)NR9R10, C(&boxH;O)â€”Oâ€”R14, R6, â€”Oâ€”R6, phenyl, Het3, C(&boxH;O)Het3 and C1-4alkyl substituted with hydroxy, C1-4alkyloxy, C(&boxH;O)â€”Oâ€”R14, â€”Yâ€”C1-4alkanediylâ€”C(&boxH;O)â€”Oâ€”R14, Het3 or NR9R10; Het represents a heterocycle selected from pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, furanyl, tetrahydrofuranyl, thienyl, thiolanyl, dioxolanyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyranyl, pyridazinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dioxanyl, dithianyl, trithianyl, triazinyl, benzothienyl, isobenzothienyl, benzofuranyl, isobenzofuranyl, benzothiazolyl, benzoxazolyl, indolyl, isoindolyl, indolinyl, purinyl, 1H-pyrazolo[3,4-d]pyrimidinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phtalazinyl, quinazolinyl, quinoxalinyl, thiazolopyridinyl, oxazolopyridinyl and imidazo[2,1-b]thiazolyl; wherein said heterocycles each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from Het2, R11 and C1-4alkyl optionally substituted with one or two substituents independently selected from Het2 and R11; Het2 represents a heterocycle selected from pyrrolyl, pyrrolinyl, imidazolyl, imidazolinyl, pyrazolyl, pyrazolinyl, triazolyl, tetrazolyl, furanyl, tetrahydrofuranyl, thienyl, thiolanyl, dioxolanyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, thiazolinyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyranyl, pyridazinyl, dioxanyl, dithianyl, trithianyl, triazinyl, benzothienyl, isobenzothienyl, benzofuranyl, isobenzofuranyl, benzothiazolyl, benzoxazolyl, indolyl, isoindolyl, indolinyl, purinyl, 1H-pyrazolo[3,4-d]pyrimidinyl, benzimidazolyl, quinolyl, isoquinolyl, cinnolinyl, phtalazinyl, quinazolinyl, quinoxalinyl, thiazolopyridinyl, oxazolopyridinyl and imidazo[2,1-b]thiazolyl; wherein said heterocycles each independently may optionally be substituted with one, or where possible, two or three substituents each independently selected from R11 and C1-4alkyl optionally substituted with one or two substituents independently selected from R11; Het3 represents a monocyclic heterocycle selected from 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, C1-4alkylcarbonyl, piperidinyl, NR12R13, C(&boxH;O)â€”Oâ€”R14, R6 and C1-4alkyl substituted with one or two substituents independently selected from hydroxy, C1-4alkyloxy, phenyl, C(&boxH;O)â€”Oâ€”R14, â€”Yâ€”C1-4alkanediylâ€”C(&boxH;O)â€”Oâ€”R14, R6 and NR12R13; Het4 represents a monocyclic heterocycle selected from pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyranyl, pyridazinyl and triazinyl.