Pyrimido¬4,5-d| pyrimidine derivatives for use as...

C - Chemistry – Metallurgy – 07 – D

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C07D 487/04 (2006.01) A61K 31/505 (2006.01) C07D 239/30 (2006.01) C07D 239/42 (2006.01)

Patent

CA 1339573

Compounds of the formula (1) : (see fig.I) or pharmaceutically acceptable salts are described, wherein R1 is C1-6alkyl, C2-6alkenyl, C3-5cycloalkylC1-6-alkyl, or C1-6alkyl substituted by 1 to 6 fluoro groups; R2 is C1-6alkylthio, C1-6alkylsulphonyl, C1-6alkoxy, hydroxy, hydrogen, hydrazino, C1-6alkyl, phenyl, -NHCOR3 wherein R3 is hydrogen or C1-6alkyl, or -NR4R5, wherein R4 and R5 together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino ring, or R4 and R5 are independently hydrogen, C3-5cycloalkyl or C1-6alkyl which is optionally substituted by -CF3, phenyl, -S(O)nC1-6alkyl wherein n is 0, 1 or 2, -OR6, -CO2R7 or -NR8R9 wherein R6 to R9 are independently hydrogen or C1-6alkyl, provided that the carbon atom adjacent to the nitrogen atom is not substituted by said -S(O)nC1-6alkyl, -OR6 or -NR8R9 groups; and (see fig.II) is a ring of sub-formula (a) or (b) : (see fig.III) (see fig.IV) The compounds of the present invention are inhibitors of a calmodulin insensitive cyclic GMP phosphodiesterase. Their use as medicaments, pharmaceutical compositions containing them and processes for their preparation are also described.

602442

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