168464-82-2

Upstream product

• 5417-82-3 (1-ethoxyethylidene)malononitrile 
• 168464-94-6 1,3-Dimethyl-6-(5-bromo-2-propoxyphenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one 
• 1026602-36-7 N-(4-Cyano-2,5-dimethyl-2H-pyrazol-3-yl)-2-propoxy-benzamide 
• 168464-99-1 1,3-Dimethyl-6-(2-propoxy-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 
• 54820-92-7 1,3-dimethyl-5-amino-1H-pyrazole-4-carbonitrile 
• 168464-57-1 1,3-Dimethyl-6-(5-cyano-2-propoxyphenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 

Relevant academic research and scientific papers

Synthesis and cyclic GMP phosphodiesterase inhibitory activity of a series of 6-phenylpyrazolo[3,4-d]pyrimidones

A series of 6-phenylpyrazolo[3,4-d]pyrimidones is described which are specific inhibitors of cGMP specific (type V) phosphodiesterase. Enzymatic and cellular activity as well as in vivo oral antihypertensive activity are evaluated. A n-propoxy group at the 2-position of the phenyl ring is necessary for activity. A series of products substituted at the 5-position in addition to the 2-n-propoxy was prepared and evaluated. This position can accommodate many unrelated groups. Amino derivatives were very potent but lacked metabolic stability. Substitution by carbon-linked small heterocycles provided both high levels of activity and stability. Cellular activity very often correlated with in vivo activity. Among the compounds, 1,3-dimethyl-6- (2-propoxy-5-methanesulfonamidophenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidin- 4-one (38) and 1-ethyl-3-methyl-6-(2-propoxy-5-(4-methylthiazol-2-yl)phenyl)- 1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one (59) displayed outstanding in vivo activities at 5 mg/kg/os and good metabolic stabilities.

Pyrazolopyrimidine Derivatives

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)mNR10C(=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.