Compounds derived from N - or - S - systems which consist of a FUSED Heterocyclic Ring Substituent.Inhibitors of phosphodiesterase Type 9, Pharmaceutical Composition and use of the compound in the treatment of Type 1 and type 2 diabtes, hyperglycemia,

摘要

Cyclic guanosine monophosphate derivatives (I) and their stereoisomers and/or prodrugs or salts are new. Cyclic guanosine monophosphate derivatives of formula (I) and their stereoisomers and/or prodrugs or salts are new. [Image] A : 8 heterocyclic derivatives e.g. purine 2-one derivative of formula (b) or 2,4,6-tirazole imidazole derivative of formula (c); ring P+C : 3-8C (hetero)cycloalkyl or (hetero)aryl (all optionally substituted with 1-3 substituents of halo, 1-5C alkyl, 1-5C alkoxy or CF 3); J : O, S, N(R 1 5), N(R 1 5)CO, CON(R 1 5), SO 2N(R 1 5) or N(R 1 5)SO 2; R 1 0CO 2H, CONR 3 0R 3 1, NR 3 0R 3 1 or N(R 1 5)SO 2R 4 0; R 1, R 2H or 1-3C alkyl; R 31-8C alkyl, 3-8C (hetero)cycloalkyl, 3-8C (hetero)cycloalkyl-methyl or (hetero)aryl (all optionally substituted with 1-3 substituents of halo, OH, oxo, 1-5C alkyl or 1-5C alkoxy); R 1 5H or 1-5C alkyl; either R 3 0, R 3 1H, 1-5C alkyl, 3-8C (hetero)cycloalkyl or (hetero)aryl (all optionally substituted with 1-3 substituents of halo, oxo, 1-5C alkyl, CO 2R 4 0, COR 4 0, OR 4 0, CONR 5 0R 5 1, NR 5 0R 5 1 or SO 2R 4 0); or NR 3 0R 3 15-8 membered heterocycloalkyl ring (the ring optionally having 1 additional heteroatom of N, O or S) (optionally substituted with 1-3 of halo, oxo, 1-5C alkyl, CO 2R 4 0, COR 4 0, OR 4 0, CONR 5 0R 5 1, NR 5 0R 5 1 or SO 2R 4 0); R 4 0H, 1-5C alkyl, 3-8C (hetero)cycloalkyl or (hetero)aryl; either R 5 0, R 5 1H, 1-5C alkyl, 3-8C (hetero)cycloalkyl or (hetero)aryl; or NR 5 0R 5 15- to 8-membered heterocycloalkyl ring (the ring optionally having 1 additional heteroatom of N,O or S); and x : 0-6. [Image] ACTIVITY : Antidiabetic; Antilipemic; Cardiovascular-Gen. MECHANISM OF ACTION : Phosphodiesterase 9 (PDE9) inhibitor. (I) were tested for PDE9 inhibitory activity using biological assays. The results showed that (I) exhibited a median inhibitory concentration value of less than 50 nM.