Patent ID: 6489328
Filing Date: 2002-12-03
Classification: A61K,A61P,C07D

Abstract:
A compound of the following formula (I): wherein:Ar1 is an aromatic or nonaromatic carbocycle, heteroaryl or heterocycle; wherein said carbocycle, heteroaryl or heterocycle is optionally substituted by one or more R1, R2 and R3; X is NH, Nâ€”C1-3alkyl, N-cyclopropyl, S or O; Y is NR13; R1 and R2 are the same or different and are selected from H, halogen, CN, NO2, C1-10 branched or unbranched saturated or unsaturated alkyl, C1-10 branched or unbranched alkoxy, C1-10 branched or unbranched acyl, C1-10 branched or unbranched acyloxy, C1-10 branched or unbranched alkylthio, aminosulfonyl, di-(C1-3)alkylaminosulfonyl, NR8R9, aryl, aroyl, aryloxy, arylsulfonyl, heteroaryl and heteroaryloxy; wherein the abovementioned R1 and R2 are optionally partially or fully halogenated or optionally substituted with one to three groups independently selected from the group consisting of oxo, OH, NR8R9, C1-6 branched or unbranched alkyl, C3-7cycloalkyl, phenyl, naphthyl, heteroaryl, aminocarbonyl and mono- or di(C1-3)alkylaminocarbonyl; R3 is selected from the group consisting of H, halogen, OH, (CH2)nNR8R9, (CH2)nCO2R10, C1-3alkyl optionally substituted with OH, C1-3 alkoxy optionally halogenated and C1-3 alkylthio; Het represents a fused heterocyclic ring having a formula A, B or C: R4 is selected from H, C1-6 alkyl branched or unbranched, saturated or unsaturated, and optionally substituted with phenyl, OH or C1-3alkoxy, C3-10-cycloalkyl, or C5-8cycloalkenyl; or R4 is selected from (CH2)mNR8R9, (CH2)mNR8COR10, (CH2)nCO2R10, (CH2)nCONR8R9, phenyl, heteroaryl or heterocycle, each phenyl, heteroaryl or heterocycle being optionally substituted with C1-3alkyl, C1-3alkoxy, (CH2)mNR8R9, OH, SO3H or halogen; R5 is selected from H, C1-10alkyl branched or unbranched, C3-10 cycloalkyl, C5-7cycloalkenyl, C2-6 alkenyl, C2-6 alkynyl, C1-6acyl, each being optionally substituted with one or more halogen, OH, oxo, CN, C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-3alkoxy, NR8R9, ureido guanidino, NR8COR10, SR10, CONR8R9, CO2R10, C3-10 cycloalkyl, C3-10cycloalkylidene, C5-7cycloalkenyl, aryloxy, arylthio, aryl, heteroaryl or heterocycle; wherein each of C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10cycloalkyl, C3-10cycloalkylidene, C5-7cycloalkenyl, aryloxy, arylthio, aryl, heteroaryl or heterocycle is optionally substituted with one or more C1-3alkyl, C1-3alkoxy, halogen, CN, NO2, amidino, guanidino, (CH2)nNR8R9, or O(CH2)2-4NR8R9; wherein one or more of the amino nitrogens in the ureido, amidino or guanidino groups in this paragraph may be optionally substituted with C1-3alkyl, phenylC0-3alkyl, C1-3alkoxy or CO2R10; or R5 is selected from CO2R10, NR8R9, CONR8R9, aryl, heteroaryl, heterocycle, aryl-COâ€”, heteroaryl-COâ€” or heterocycle-COâ€”, wherein each aryl, heteroaryl or heterocycle is optionally substituted with one to three: C1-3alkoxy, halogen, NO2, CN, S(O)pNR8R9, CO0-3alkylS(O)p, NR8R9, (CH2)nCO2R10, (CH2)nCONR8R9, CO(CH2)nNR8R9, O(CH2)2-4NR8R9, ureido, guanidino, cycloalkyl, aryl, heteroaryl, heterocycle, cycloalkyl-Zâ€”, aryl-Zâ€”, heteroaryl-Zâ€”, heterocycle-Zâ€”, or C1-3alkyl optionally substituted with phenyl or NR8R9, wherein Z is a bridging group selected from C1-10 alkylene branched or unbranched, CO, S(O)p, O, S, NH, CONH, NHCO, COO or OOC, and wherein each cycloalkyl, aryl, heteroaryl or heterocycle is optionally substituted with NO2, C1-3alkyl, C1-3alkoxy, halogen, CO2R10, (CH2)nNR8R9, O(CH2)2-4NR8R9, ureido or guanidino, wherein one or more of the amino nitrogens in the ureido or guanidino groups in this paragraph may be optionally substituted with C1-3alkyl, phenylC0-3alkyl or C1-3alkoxy; and wherein each alkyl, alkoxy and phenyl in this paragraph is optionally partially or fully halogenated; or R5 is a C6-12 bridged- or spiro-bicyclic ring system, optionally having one or two double bonds in the ring system, and wherein up to 3 carbon atoms in the ring system may be replaced by heteroatoms selected from N, O and S; and wherein said ring system may be optionally substituted with C1-3alkyl, C1-3alkoxy, halogen, CO2R10, ureido, guanidino, amidino, (CH2)nNR8R9, or O(CH2)2-4NR8R9; wherein one or more of the amino nitrogens in the ureido, guanidino or amidino groups in this paragraph may be optionally substituted with C1-3alkyl, phenylC0-3alkyl or C1-3alkoxy; R6 is selected from H, C1-6alkyl branched or unbranched, C2-6 alkenyl branched or unbranched, CO2R10, C3-8cycloalkyl, C3-8cycloalkenyl, aryl, arylC1-3alkyl, heteroaryl and heterocyclyl; wherein said C1-6alkyl, C2-6alkenyl, C3-8cycloalkyl, C3-8cycloalkenyl, aryl, arylC1-3alkyl, heteroaryl or heterocyclyl are optionally substituted with OH, C1-3alkoxy, C1-3acyloxy, CO2R10, NR11R12, O(CH2)2-4NR11R12, aryl, heteroaryl or heterocyclyl; R7 is H or C1-6alkyl; R8 and R9 are the same or different and are each independently selected from H, OH, CO2R10, C1-10 acyl branched or unbranched, C1-3alkoxy, C1-6alkyl branched or unbranched, C3-6alkenyl, C3-8cycloalkyl, aryl, arylC1-3alkyl, aroyl, heteroaryl or heterocycle; wherein said alkyl, cycloalkyl, aryl, arylC1-3alkyl, aroyl, heteroaryl or heterocycle are optionally substituted with OH, C1-3alkoxy, C1-3acyloxy, CO2R10, NR11R12, O(CH2)2-4NR11R12, aryl or heteroaryl; or R8 and R9 together form a 3-7 member alkylene chain completing a ring about the N atom to which they are attached; wherein said alkylene chain is optionally interrupted by O, S(O)p, NCOR10, NCO2R10, NR11 or NC(&boxH;NR11)NR11R12; and wherein said ring is optionally substituted by C1-3 alkyl, C1-3alkoxy, OH or â€”(CH2)nNR11R12; R10 is selected from H, C1-6alkyl, C3-8cycloalkyl, wherein each alkyl or cycloalkyl is optionally substituted with phenyl, OH, C1-3alkoxy, C1-3alkanoyloxy or NR11R12, or R10 is phenyl optionally substituted with one to three C1-3alkyl, C1-3alkoxy, halogen, (CH2)mNR8R9, (CH2)nCONR8R9 or O(CH2)2-4NR8R9; R11 and R12 are each independently selected from H and C1-6 alkyl optionally substituted with C1-3alkoxy, OH or phenyl; or R11 and R12 together form a chain completing a ring, said chain is (CH2)4-5 or (CH2)2O(CH2)2; R13 is H or C1-3alkyl; P and Q are each CH; m is 1-4; n is 0-3; and p is 0-2; wherein one or more of the primary amine or secondary amine nitrogen atoms in any of the R4, R5, R6 and R7 substituent groups may optionally be protected by a protecting group; or a pharmaceutically acceptable derivative thereof.