EP0636626A1 — Pyrazolopyrimidine Derivatives

USPTO Abstract

Pyrazolo[3,4-d]pyrimidin-4-one derivatives of formula (I) and salts and solvates thereof are described, in which: R¹ represents arylmethyl or C₁₋₆alkyl optionally substituted by one or more fluorine atoms; R² represents methyl; R³ represents C₂₋₄alkyl; R⁴ represents nitro, cyano, C₁₋₆alkoxy, C(=X)NR⁶R⁷, NR⁸R⁹, (CH₂) m NR¹⁰C(=Y)R¹¹ or a 5-membered heterocyclic ring selected from thienyl, thiazolyl and 1,2,4-triazolyl each ring optionally substituted by a C₁₋ ₄alkyl or aryl group; or when R¹ is arylmethyl or C₁₋₆alkyl substituted by one or more fluorine atoms then R⁴ may also represent hydrogen; R⁵ represents hydrogen or C₁₋₆alkyl; R⁶ represents hydrogen or C₁₋₆alkyl; R⁷ represents hydrogen, amino, hydroxyl, C₁₋₆alkyl, aryl or arylC₁₋₄alkyl; R⁸ represents hydrogen or C₁₋₆alkyl; R⁹ represents hydrogen, C₁₋₆alkyl, SO₂R¹², CO₂R¹², C(=NCN)SR¹² or C(=NCN)NR¹³R¹⁴; R¹⁰ represents hydrogen or C₁₋₆alkyl; R¹¹ represents C₁₋₆alkyl optionally substituted by one or more halogen atoms, or R¹¹ represents aryl, arylC₁₋₄alkyl, thienyl, NR¹⁵R¹⁶, CH₂NR¹⁷R¹⁸ or R¹⁰ and R¹¹ together represent -A(CH₂) n -; R¹² represents C₁₋₆alkyl, aryl or arylC₁₋₄alkyl; R¹³ represents hydrogen or C₁₋₆alkyl; R¹⁴ represents hydrogen, C₁₋₆alkyl, aryl, arylC₁₋₄alkyl or R¹³ and R¹⁴ together with the nitrogen atom to which they are attached form a morpholine, piperazine or N-C₁₋₄alkylpiperazine ring; R¹⁵ represents hydrogen or C₁₋₆alkyl or R¹⁰ and R¹⁵ together represent -A(CH₂) n -; R¹⁶ represents hydrogen, C₁₋₆alkyl, aryl, arylC₁₋₄alkyl, CO₂R¹², CH₂CO₂R¹² or R¹⁵ and R¹⁶ together with the nitrogen atom to which they are attached form a morpholine, piperazine or N-C₁₋₄alkylpiperazine ring; R¹⁷ represents hydrogen or C₁₋₆alkyl; R¹⁸ represents hydrogen, C₁₋₆alkyl, aryl, arylC₁₋₄alkyl, COR¹² or R¹⁷ and R¹⁸ together with the nitrogen atom to which they are attached form a morpholine, piperazine or N-C₁₋₄alkylpiperazine ring; A represents CH₂ or C=O; m represents zero or 1; n represents 1,2 or 3; X represents S or NH, or when R⁷ represents amino then X may also represent O; Y represents O or S; for use in therapy. These compounds are potent and selective inhibitors of cyclic guanosine 3',5'-monophosphate specific phosphodiesterase (cGMP specific PDE) and are useful in a variety of therapeutic areas, including the treatment of cardiovascular disorders.