Patent EA-004982-B1 (EA)
Title: PYRAZOLO[4,3-d]PYRIMIDINE DERIVATIVES
Inventor: BUNNAGE MARK EDWARD
IPC: A61P15/12
Filed: 2000-10-11
Abstract: 1. A compound of the formula (I): or a pharmaceutically or veterinarily acceptable salt, or a pharmaceutically or veterinarily acceptable solvate or pro-drug thereof, wherein R<1> is C1 to C6 alkyl or C3 to C6 alkenyl, C3 to C6 cycloalkyl or C4 to C6 cycloalkenyl wherein said alkyl group may be branched or straight chain and wherein when R<1> is C1 to C3alkyl said alkyl group is substituted by; and wherein when R<1> is C4 to C6 alkyl, C3 to C6 alkenyl or C3 to C6 cycloalkyl said alkyl, alkenyl or cycloalkyl group is optionally substituted by; one or more substituents selected from: hydroxy; C1 to C4alkoxy; C3 to C6 cycloalkyl; phenyl substituted with one or more substituents selected from C1 to C3 alkyl, C1 to C4 alkoxy, C1 to C4 haloalkyl, C1 to C4 haloalkoxy, halo, CN, NO2, NHR<11>, NHCOR<12>, NHSO2R<12>, SO2R12, SO2NHR", COR<11> or CO2R<11> wherein said haloalkyl and haloalkoxy groups contain one or more halo atoms; NR<7>R<8>, CONR<7>R<8> or NR<7>COR<11> wherein R<7> and R<8> are each independently selected from H, C1 to C4 alkyl, C3 to C4 alkenyl, CO2R<9> or SO2R<9> and wherein said alkyl or alkenyl groups are optionally substituted by C1 to C4 haloalkyl or C1 to C4 haloalkoxy; Het<1>; Het<2> or Het<3>; or R<1> is Het<4> or phenyl wherein said phenyl group is optionally substituted by one or more substituents selected from C1 to C4 alkyl, C3 to C4 alkenyl, C1 to C4 alkoxy, halo, CN, CF3, OCF3, NO2, NHR<11>, NHCOR<12>, NHSO2R<12>, SO2R<12>, SO2NHR<11>, COR<11>, CO2R<11>; R<2> is C1 to C6 alkyl, C3 to C6 alkenyl or (CH2)n(C3 to C6 cycloalkyl) wherein n is 0,1 or 2; R<13> is OR<3> or NR<5>R<6>; R<3> is C1 to C6 alkyl optionally substituted with one or two substituents selected from C3 to C5 cycloalkyl, hydroxy, C1 to C4 alkoxy, benzyloxy, NR<5>R<6>, phenyl, Het<1>, Het<2>, Het<3> or Het<4> wherein the C1 to C6 alkyl and C1 to C4 alkoxy groups may optionally be terminated by a haloalkyl group such as CF3 and wherein the C3-C5 cycloalkyl group may optionally be substituted by C1-C4 alkyl, hydroxy or halo; C3 to C6 cycloalkyl; Het<1>, Het<2>, Het<3> or Het4; R<4> is apiperazin-1-ylsulphonyl group having a substituent R<10> at the 4 position of the piperazinyl group wherein said piperazinyl group is optionally substituted with one or two C1 to C4 alkyl groups and is optionally in the form of its 4-N-oxide; R<5> and R<6> are each independently selected from H and C1 to C4 alkyl optionally substituted with C3 to C5 cycloalkyl or C1 to C4 alkoxy, or, together with the nitrogen atom to which they are attached, form an azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl group; R<7> and R<8> are each independently selected from H, C1 to C4 alkyl, C3 to C4 alkenyl, CO2R<9> or SO2R<9>; R<9> is C1 to C4 alkyl optionally substituted with C1 to C4 haloalkyl, C1 to C4 haloalkoxy or phenyl wherein said phenyl group is optionally substituted by one or more substituents selected from C1 to C4 alkyl optionally substituted by C1 to C4 haloalkyl or C1 to C4 haloalkoxy, C1 to C4 alkoxy, halo, CN, NO2, NHR<11>, NHCOR<12>, NHSO2R<12>, SO2R<12>, SO2NHR<11>, COR<11> or CO2R<11>; R<10> is H; C1 to C4 alkyl optionally substituted with one or two substituents selected from hydroxy, NR<5>R<6>, CONR<5>R<6>, phenyl optionally substituted with C1 to C4 alkyl or C to C4 alkoxy; C3 to C6 alkenyl or Het<4>; R<11> is H, C1 to C4 alkyl, C3 to C4 alkenyl, CO(C1 to C4 alkyl) or C1 to C4 haloalkyl; R<12> is C1 to C4 alkyl, C3 to C4 alkenyl, C1 to C4 haloalkyl or C1 to C4 haloalkoxy; Het<1> is an N-linked 4-, 5- or 6-membered nitrogen-containing heterocyclic group optionally containing one or more further heteroatoms selected from S, N or O; Het<2> is a C-linked 5-membered heterocyclic group containing an O, S or N heteroatom optionally containing one or more heteroatoms selected from N, O or S; Het<3> is a C-linked 6-membered heterocyclic group containing an O or S heteroatom optionally containing one or more heteroatoms selected from O, S or N or Het<3> is a C-linked 6-membered heterocyclic group containing three N heteroatoms; Het<4> is a C-linked 4-, 5- or 6-memberedheterocyclic group containing one, two or three heteroatoms selected from S, O or N; and wherein any of said heterocyclic groups Het<1>, Het<2>, Het<3> or Het<4> may be saturated, partially unsaturated or aromatic and wherein any of said heterocyclic groups may be optionally substituted with one or more substituents selected from C1 to C4 alkyl, C3 to C4 alkenyl, C1 to C4 alkoxy, halo, CF3, CO2R<11>, COR<11>, SO2R<12>, NHR<11> or NHCOR<12> and/or wherein any of said heterocyclic groups is benzo-fused; with the provisos that (a) when R<1> is C3 to C3 alkyl, then Het<1> is not morpholinyl) or piperidinyl, and (b) when R<1> is C1 to C3, alkyl substituted by phenyl then said phenyl group is not substituted by C1 to C4 alkoxy, CN, halo, CF3, OCF3 or C1 to C4 alkyl. 2. A compound according to claim 1, wherein R<1> is C1 to C6 alkyl or C3 to C6 alkenyl, wherein said alkyl or alkenyl groups may be branched or straight chain and wherein when R<1> is C3 to C6 cycloalkyl or C4 to C6 cycloalkenyl, and wherein when R<1> is C1 to C3 alkyl said alkyl group is substituted by; and wherein when R<1> is C4 to C6 alkyl, C3 to C6alkenyl, C3 to C6-cycloalkyl or C4 to C6cycloalkenyl said alkyl, alkenyl, cycloalkyl or cycloalkenyl group is optionally substituted by; one or more substituents selected from: hydroxy; C1 to C4 alkoxy; C3 to C4 cycloalkyl; phenyl substituted with one or more substituents selected from C1 to C3 alkyl, C1 to C4 alkoxy, C1 to C4 haloalkyl or C1 to C4 haloalkoxy, halo, CN, NO2, NHR<11>, NHCOR<12>, NHSO2R<12>, SO2R12, SO2NHR", COR<11> or CO2R<11> wherein said haloalkyl and haloalkoxy groups contain one or more halo atoms; NR<7>R<8>, CONR<7>R<8> or NR<7>COR<11>, a Het<1> group which is an N-linked 4-membered N-containing heterocyclic group; a Het<2> group which is a C-linked 5-memberedheterocyclic group containing an O, S or N heteroatom optionally containing one or more heteroatoms selected from N, O or S; a Het<3> group which is a C-linked 6-membered heterocyclic group containing an O or S heteroatom optionally containing one or more heteroatoms. Selected from O, S or N or a Het<3> group which is a C-linked 6-membered heterocyclic group containing three N heteroatoms; wherein R<7>, R<8>, R<11> and R<12> are as previously defined herein or R<1> is a Het<4> group which is a C-linked 4-or 5-membered heterocyclic group containing one heteroatom selected from S, O or N; a Het<4> group which is a C-linked 6-membered heterocyclic group containing one, two or three heteroatoms selected from S or O; a Het<4> group which is a C-linked 6-membered heterocyclic group containing three nitrogen heteroatoms; a Het<4> group which is a C-linked 6 membered heterocyclic group containing one or two nitrogen heteroatoms which is substituted by one or more substituents selected from C1 to C4alkyl, C1 to C4 alkoxy, CO2R<11>, SO2R<12>, COR<11>, NHR<11> or NHCOR<12> and optionally including a further heteroatom selected from S, O or N, wherein any of said heterocyclic groups Het<1>, Het<2>, Het<3> or Het<4> is saturated, partially unsaturated or aromatic as appropriate and wherein any of said heterocyclic groups is optionally substituted with one or more substituents selected from C1 to C4 alkyl, C3 to C4 alkenyl, C1 to C4 alkoxy, halo, CO2R<11>, SO2R<12>, COR<11> or NHR<11> wherein R<11> is as defined hereinbefore and/or wherein any of said heterocyclic groups is benzo-fused; or R<1> is phenyl substituted by one or more substituents selected from CF3, OCF3, SO2R<12> or CO2R<12> wherein R<12> is C1 to C4 alkyl which is optionally substituted by phenyl, C1 to C4 haloalkyl or C1 to C4 haloalkoxy wherein said haloalkyl and haloalkoxy groups contain one or more halo atoms; R<2> is C1 to C6 alkyl; R<13> is OR<3>; R<3> is C1 to C6 alkyl optionally substituted with one or two substituents selected from C3 to C5cycloalkyl, hydroxy, C1 to C4 alkoxy, benzyloxy, NR<5>R<6>, phenyl, furanyl, tetrahydrofuranyl, or pyridinyl wherein said C1 to C6 alkyl and C1 to C4 alkoxy groups may optionally be terminated by a haloalkyl group such as CF3; or R<3> is C3 to C6cycloalkyl, 1-(C1 to C4 alkyl) piperidinyl, tetrahydrofuranyl or tetrahydropyranyl; R<4> is a piperazin-1-yl-sulphonyl group having a substituent R<10> at the 4 position of the piperazinyl group wherein said piperazinyl group is optionally substituted with one or two C1 to C4 alkyl groups and is optionally in the form of its 4-N-oxide; R<5> and R<6> are each independently selected from H and C1 to C4 alkyl optionally substituted with C3 to C5 cycloalkyl, or C1 to C4 alkoxy, or, together with the nitrogen atom to which they are attached, form an azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl group; and R<10> is H; C1 to C4 alkyl optionally substituted with one or two substituents selected from hydroxy, NR<5>R<6>, CONR<5>R<6>, phenyl optionally substituted with C1 to C4 alkyl or C1 to C4 alkoxy, C3 to C6 alkenyl; Het<4>; with the proviso that when R<1> is C1 to C3 alkyl substituted by phenyl, then said phenyl group is not substituted by C1 to C4 alkoxy; CN; CF3; halo; OCF3; or C1 to C4 alkyl. 3. A compound according to claim 2 wherein R<1> is C1 to C6alkyl wherein said alkyl may be branched or straight chain or R<1> is C3 to C6 cycloalkyl and wherein when R<1> is C1 to C3alkyl, said alkyl group is substituted by; and wherein when R' is C4 to C6alkyl or C3 to C6 cycloalkyl said alkyl or cycloalkyl group is optionally substituted by; one or more substituents selected from : hydroxy; C1 to C2 alkoxy; C3 to C5 cycloalkyl; NR<7>R<8>, NR<7>COR<11> or COR<11> wherein R<7> and R<8> are each independently selected from H, C1 to C4 alkyl or CO2R<9> wherein R<9> and R<11>are as previously defined herein; a Het<1> group which is an N-linked 4-membered N-containing heterocyclic group; a Het<3> group which is a C-linked 6-memberedheterocyclic group containing an O or S heteroat