5,7-DIAMINOPIRAZOLO (4,3-D) USEFUL PYRIMIDINS IN THE TREATMENT OF HYPERTENSION.

摘要

A compound of formula (I) ** see formula ** in which R1 is a cyclic group that is selected from RA, RB, RC and RD, each of which is optionally substituted with one or more R7 groups; R2 is hydrogen or C1-C2 alkyl; R3 and R4 are each independently C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl or C3-C10 cycloalkyl, each of which is optionally substituted with one or more R8 groups, or RE, which is optionally substituted with one or more R9 groups, or hydrogen; or -NR3R4 form RF, which is optionally substituted with one or more R10 groups; R5 is C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl, each of which is optionally substituted with one or more groups selected from hydroxy, C1- alkoxy C6, C1-C6 haloalkoxy, C3-C7 cycloalkyl and C3-C7 cycloalkoxy, or hydrogen; R6A, which may be attached to N1 or N2, is R6A; R6A is C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with C1-C6 alkoxy, (C3-C6 cycloalkyl) C1-C6 alkoxy, C1- haloalkoxy C6 or a cyclic group selected from RJ, RK, RL and RM, or R6A is RN, C3-C7 cycloalkyl or C3-C7 halocycloalkyl, each of which is optionally substituted with C1-C6 alkoxy or C1-C6 haloalkoxy . R7 is halo, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, oxo, phenyl, OR12, OC (O) R12, NO2, NR12R13, NR12C (O) R13, NR12CO2R14, C (O) R12, CO2R12, CONR12R13 or CN; R8 is halo, phenyl, C1-C6 alkoxy phenyl, OR12, OC (O) R12, NO2, NR12R13, NR12C (O) R13, NR12CO2R14, C (O) R12, CO2R12, CONR12R13, CN, C3-C6 cycloalkyl, RG or RH, the last two of which are optionally substituted with one or more R9 groups; R9 is C1-C6 alkyl, C1-C6 haloalkyl or CO2R12; R10 is halo, C3-C10 cycloalkyl, C3-C10 halocycloalkyl, phenyl, OR12, OC (O) R12, NO2, NR12R13, NR12C (O) R13, NR12CO2R14, C (O) R12, CO2R13, CONR12R13, CN, oxo, C1-C6 alkyl or C1-C6 haloalkyl, the last two of which are optionally substituted with R11; R11 is OH, phenyl, NR12R13 or NR12CO2R14; R12 and R13 are each independently hydrogen, C1-C6 alkyl or C1-C6 haloalkyl; R14 is C1-C6 alkyl or C1-C6 haloalkyl; RA and RJ are each independently a C3-C10 cycloalkyl or C3-C10 cycloalkenyl group, each of which may be either monocyclic or, when there is an appropriate number of ring atoms, polycyclic and which may be condensed to (a) a monocyclic aromatic ring that is selected from a benzene ring and a 5- or 6-membered heteroaromatic ring containing up to three heteroatoms that are selected from nitrogen, oxygen and sulfur, or (b) a 5-heteroalicyclic ring , 6 or 7 members containing up to three heteroatoms that are selected from nitrogen, oxygen and sulfur; RB and RK are each independently a phenyl or naphthyl group, each of which can be condensed to (a) a C5-C7 cycloalkyl or C5-C7 cycloalkenyl ring, (b) a 5, 6 heteroalicyclic ring, or 7 members containing up to three heteroatoms that are selected from nitrogen, oxygen and sulfur, or (c) a 5 or 6 member heteroaromatic ring containing up to three heteroatoms that are selected from nitrogen, oxygen and sulfur; RC, RL and RN are each independently a monocyclic ring system or, when there is an appropriate number of atoms in the ring, saturated or partially unsaturated polycyclic containing between 3 and 10 atoms in the ring, of which at least one is a heteroatom that is selected from nitrogen, oxygen and sulfur, said ring can be condensed to a C5-C7 cycloalkyl or C5-C7 cycloalkenyl group or a monocyclic aromatic ring that is selected from a benzene ring and a heteroaromatic ring of 5 or 6 members containing up to three heteroatoms that are selected from nitrogen, oxygen and sulfur; RD and RM are each independently a 5 or 6 member heteroaromatic ring containing up to three heteroatoms independently selected from nitrogen, oxygen and sulfur, said ring can also be condensed to (a) a second 5 or 6 member heteroaromatic ring containing up to three heteroatoms that are selected from nitrogen, oxygen and sulfur; (b) a C5-C7 cycloalkyl or C5-C7 cycloalkenyl ring; (c) a 5, 6, or 7 membered heteroalicyclic ring containing up to three heteroatoms that are selected from nitrogen, oxygen and sulfur; or (d) a benzene ring; RE, RF and RG are each independently a monocyclic ring system or, when there is an appropriate number of atoms in the ring, saturated polycyclic containing between 3 and 10 atoms in the ring, of which at least one is a heteroatom which is selected from nitrogen, oxygen and sulfur; and RH is a 5- or 6-membered heteroaromatic ring containing up to three heteroatoms independently selected from nitrogen, oxygen and sulfur; a tautomer thereof or a pharmaceutically acceptable salt, solvate or polymorph of said compound or tautomer.