159256-61-8

Upstream product

• 6289-02-7 1-phenylpyrazolo<3,4-d>pyrimidine-4,6(5H,7H)-dithione 
• 5398-24-3 2-bromobutyramide 
• 6289-02-7 1-phenyl-5H,7H-pyrazolo<3,4-d>pyrimidine-4,6-dithione 

Downstream Products

• 181702-35-2 2-(4-Methylsulfanyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-ylsulfanyl)-butyramide 

Relevant academic research and scientific papers

Pyrazolo[3,4-d]pyrimidines: C4, C6 substitution leads to adenosine A1 receptor selectivity

Following the demonstration that substitution of 1-phenylpyrazolo[3,4-d]pyrimidines at C6 with thioethers containing amide moieties could effect adenosine A1 and A(2a) receptor selectivity, two compounds with high A1 selectivity have been obtained by a combined C4, C6 substitution. This further demonstrates that distal moieties at C6 can effect selectivity and that C4 substituents have an important role.

Synthesis and structure-activity relationship of pyrazolo[3,4- d]pyrimidines: Potent and selective adenosine A1 receptor antagonists

A series of 12 substituted 1-phenylpyrazolo[3,4-d]pyrimidines were synthesized and evaluated for rat brain adenosine A1 and A(2a) receptor binding affinity. Substituents at C-4 and C-6 were varied in order to define these regions in terms of molecular recognition by the receptor subtypes. At C-4, the effects of a mercapto, methylthio, and amino substituent were evaluated, while at C-6, amides with varying alky] groups extending from the α-carbon were examined. This study identified both potent and selective adenosine A1 receptor antagonists. The most potent of the 12 compounds was α-[(4-amin-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl)thio]hexanamide (14); with an A1 K(i) of 0.939 nM and an A(2a) K(i) of 88.3 nM, this compound is 94- fold A1 selective. The most selective of the 12 compounds was α-[[4- (methylthio)-1-phenylpyrazolo[3,4-d]pyrimidin6-yl]thio]hexanamide (10); with an A1 K(i) of 6.81 nM and an A(2a) K(i) > 40 000 nM, this compound is >5900- fold A, selective. The structure-activity relationships for the complete series has identified discrete structural differences between the A1 and A(2a) receptors with respect to the binding of pyrazolo[3,4-d]pyrimidines. This study resulted in prediction that increased A1 affinity could be achieved by incorporation of NH-alkyl substituents at C-4. This was confirmed by synthesis of α-[[4-(methylamino)-1-phenylpyrazolo[3,4-d]pyrimidin-6- yl]thio1]hexanamide (15) which was found to have an A1 K(i) of 0.745 nM.

Pyrazolo[3,4-d]pyrimidines with adenosine-like binding affinities

The A21 receptor extracelluar site and the A2 receptor extracellular site of adenosine analogues are structurally different and that binding orientations of adenosine or adenosine analogues are different at these sites and this may be used to determine th