FIELD: pharmacology.
SUBSTANCE: invention relates to a compound of formula I 
in which each of Y and Z independently represents -CH- or -N-, with the proviso that at least one substituent Y or Z is -N-; M is 0-5; each of R1 is independently selected from H, halogen, -CN, -C1-6alkyl, -C1-6alkynyl-C1-6haloalkyl, -C1-6thioalkyl, -C1-6thiogaloalkyl, -C1-6alkoxy, -C1-6haloalkoxy, -SO2C1-6alkyl, aryl, pyrazole and 2-oxopyrrolidine; or two R1 substituents are on adjacent carbon atoms and (together with the carbon atoms to which they are attached) form a 5-6 membered saturated or unsaturated monocyclic ring system containing 2 oxygen or nitrogen atoms, wherein the said ring system is optionally substituted by -C1-6alkyl; each of R3 and R4 is independently selected from the group consisting of H, halogen, -C1-6alkyl substituted by one or two groups independently selected from -C1-6alkoxy, -C1-6alkoxy-C1-6alkoxy, and -OH; -C1-6haloalkyl substituted by -OH, -C1-6alkenyl of optionally substituted -C1-6alkoxy, -CH2O-phenyl, -C(O)CH3, -CH(OH)(CF3), -(CR10R11)0-3NR12R13, phenyl, and 6-membered heteroaryl having 1 to 2 heteroatoms selected from N, wherein each phenyl and heteroaryl are substituted by one or two moieties, each independently selected from the group consisting of -CH3, -OCH3, and oxo; each of R10 and R11 is independently selected from the group consisting of: -H, -F, -CF3, and OH; each of R12 and R13 is independently selected from the group consisting of -H, -C1-6alkyl optionally substituted by -C1-6alkoxy, N(C1-6alkyl)2; -CO2-benzyl; -C1-6alkyl(phenyl), -C1-6alkyl(4 to 5-membered heterocycloalkyl having 1 heteroatom selected from O), phenyl optionally substituted by -C1-6alkyl; -C1-6cycloalkyl optionally substituted by amino; 6-membered heterocycloalkyl having 1 heteroatom selected from N, O, optionally substituted -C1-6alkyl; or R12 and R13, taken together with the nitrogen atom to which they are attached, form a heterocycloalkyl. The invention also relates to individual compounds, pharmaceutical compositions, methods for diseases treatment, application of a compound or composition, methods for PDE1 enzymatic activity modulation.
EFFECT: new compounds of formula I are obtained that have a selective effect on PDE1.
63 cl, 3 dwg, 173 ex
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