Patent RU-2659779-C2 (RU)
Inventor: BRAJTENBUKHER Dzhejms
IPC: C07D491/147
Filed: 2013-06-18
Granted: 2018-07-04
Abstract: FIELD: medicine. 
     SUBSTANCE: invention relates to a novel compound of formula I or a pharmaceutically acceptable salt thereof having a selective impact on PDE1. In formula I  
        X represents -CH- or -N-; Y - O- or -S-; M is 0-3; each of R 1  is independently selected from the group consisting of: H, halogen, -C 1-6 alkyl, -C 1-6 haloalkyl, -C 1-6 alkoxy, -C 1-6 haloalkoxy, and phenyl; each of R 3  and R 4  is independently selected from the group consisting of: -H; halogen; -C 1-6 alkyl; -C 1-6 haloalkyl; -CH 2 OH; -C 1-6 alkoxy; -C 1-6 haloalkoxy; optionally substituted 5- or 7-membered heteroaryl having 1-3 heteroatoms selected from: N, O, or S, in which the substituents are independently selected from C 1 -C 6 alkyl, HOCH 2 , halogen, -CH 2 N(C 1 -C 4 alkyl)-C(=O)-, N(C 1 -C 4 alkyl) 2 , -CH 2 N(C 1 -C 4 alkyl) 2 , benzyl, -CH 2 -5-7-membered monoheterocycloalkyl having 1 to 2 heteroatoms selected from N, O, optionally substituted C 1 -C 4 alkyl, oxo, C 1 -C 4 alkylsulfonyl, or -CH 2 -5-6-membered monoheterocycloalkyl having a nitrogen atom in the ring condensed with a benzene ring, or -CH 2 -7-9-membered bicyclic heterocycloalkyl having 1 to 2 heteroatoms selected from N or O; -(C 1 -C 6 alkyl)phenyl; -(C 1 -C 6 alkyl)-5-6-membered heteroaryl having 1 to 2 heteroatoms selected from N and O, and -(CR 10 R 11 ) 1-3 NR 12 R 13 ; or R 3  and R 4 , taken together with the carbon atoms to which they are attached, form a saturated or unsaturated monocyclic ring system having the following structure:   where D is a bond, or -O-, or -N(R 9 )-, where R 9  represents -H, -C 1-6 alkyl, -halogen-C 1-6 alkyl, -C 1-6 alkylthiomethyl, -C 1-6 alkyl-SO 2 methyl, -C 1-6 alkoxyC 1-6 alkyl, -halogen 1-6 alkoxyalkyl, -C 1-6 alkylphenyl, -C 1-6 alkyl (C 3-6 cycloalkyl), -C 1-6 alkyl (4-6-membered saturated heterocycloalkyl with 1-2 heteroatoms, selected from N and O), -C 1-6 alkyl(phenyl, optionally condensed with 5-6 membered saturated heterocycloalkyl with 1-2 heteroatoms, selected from O), C 1-6 alkyl (5-6 membered heteroaryl with 1 to 3 heteroatoms selected from N, S or -SO 2 ) or 4-6 membered heterocycloalkyl with heteroatoms selected from O, S, wherein each of said substituents is optionally substituted with -Cl, -F or -CH 3 ; each of m and n is independently 0-3 upon condition that the sum of m and n is 1-3, when D is -O-, -N(R 9 ) -, or is 2-3 when D represents a bond; and with the proviso that when D is a bond, R 1  does not represent -Cl in the para position; each of R 5 , R 6 , R 7 , R 8  is independently selected from the group consisting of: -H, -C 1-6 alkyl, -C 1-6 haloalkyl, -OH, -C 1-6 alkoxy, -C 1-6 haloalkoxy; each of R 10  and R 11  is independently selected from the group consisting of: -H, -C 1-6 alkyl, -hydroxyC 1-6 alkyl, -C 1-6 alkoxyC 1-6 alkyl, CH 2 OH, -OH, -COCH 3 , and -SO 2 CH 3 ; each of R 12  and R 13  is independently selected from the group consisting of: -H, -C 1-6 alkyl, -C 3-6 cycloalkyl, -C 1-6 alkyl(phenyl), -C 1-6 alkyl (5-6 membered heteroaryl with 1-2 heteroatoms selected from N and O), and -CH 2 CON (C 1-6 alkyl) 2 ; or R 12  and R 13 , taken together with the nitrogen atom to which they are attached form a 5-7 membered mono- or 7-9 membered bicyclic heterocycloalkyl ring with 1-2 heteroatoms selected from N and O, optionally substituted with one or two R 14 , where each R 14  is independently selected from the group consisting of -H and -C 1-6 alkyl. 
     EFFECT: compounds can be used in the treatment of a disease or disorder selected from the group comprising a variety of diseases and disorders, including cognitive deficits associated with diseases and disorders of the central nervous system, neurological disorders, cardiovascular disorders, renal disorders, hematologic disorders, disorders of the gastrointestinal tract and liver, cancerous disorders and neurodegenerative disorders. 
     56 cl, 1 tbl, 224 ex