1221499-70-2

Upstream product

• 728042-77-1 5-amino-4-imino-2-methyl-2H-4,5-dihydropyrazolo[3,4-d]pyrimidine 
• 1345017-70-0 {[(2Z)-2-benzylidene-1-methylhydrazino]methylene}-malononitrile 
• 159979-75-6 4-cyano-3-[(ethoxymethylene)amino]-1-methylpyrazole 
• 420-04-2 CYANAMID 
• 1221500-22-6 C₁₂H₁₁BrN₆ 

Downstream Products

• 1221499-82-6 N-[2-(4-bromophenyl)-8-methylpyrazolo[4,3-e][1,2,4]triazolo-[1,5-c]pyrimidin-5-yl]benzamide 
• 1221499-92-8 N-[2-(4-bromophenyl)-8-methylpyrazolo[4,3-e][1,2,4]triazolo-[1,5-c]pyrimidin-5-yl]phenylacetamide 
• 1345017-80-2 N-(2-(4-bromophenyl)-8-methylpyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)-N'-phenylurea 
• 1345017-87-9 N-(2-(4-bromophenyl)-8-methylpyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)-N'-(4-fluorophenyl)-urea 
• 1345017-91-5 N-(2-(4-bromophenyl)-8-methylpyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl)-N'-(4-methoxyphenyl)-urea 

Relevant academic research and scientific papers

Does the combination of optimal substitutions at the C2-, N 5- and N8-positions of the pyrazolo-triazolo-pyrimidine scaffold guarantee selective modulation of the human A3 adenosine receptors?

In an attempt to study the optimal combination of a phenyl ring at the C2-position and different substituents at the N5- and N8-positions towards the selective modulation of human A3 adenosine receptors (hA3AR), we synthesized a new series of 2-para-(un)substituted-phenyl-pyrazolo-triazolo-pyrimidines bearing either a methyl or phenylethyl at N8 and chains of variable length at N 5. Through biological evaluation, it was found that the majority of the compounds had good affinities towards the hA3AR in the low nanomolar range. Compound 16 possessed the best hA3AR affinity and selectivity profile (KihA3 = 1.33 nM; hA 1/hA3 = 4880; hA2A/hA3 = 1100) in the present series of 2-(substituted)phenyl-pyrazolo-triazolo-pyrimidine derivatives. In addition to pharmacological characterization, a molecular modeling investigation on these compounds further elucidated the effect of different substituents at the pyrazolo-triazolo-pyrimidine scaffold on affinity and selectivity to hA3AR.

The significance of 2-furyl ring substitution with a 2-(para -substituted) aryl group in a new series of pyrazolo-triazolo-pyrimidines as potent and highly selective hA3 adenosine receptors antagonists: New insights into structure-affinity relationship and receptor-antagonist recognition

Among the heterocyclic structures identified as potent human A3 (hA3) adenosine receptor's antagonists, we have demonstrated that the new pyrazolo-triazolo-pyrimidines, bearing an aryl group in replacement of the C2-furyl ring, not only confer a good pharmacological profile (with significantly enhanced selectivity against other adenosine receptor subytpes) but also overcome the metabolic transformation of the furan ring into toxic intermediates. All the synthesized [2-(para-substituted) phenyl]-pyrazolo- triazolo-pyrimidines showed affinity at the hA3 receptor in the low nanomolar range. The most potent derivative of the series presented better affinity and excellent selectivity (compound 31, Ki hA3 = 0.108 nM; hA1/hA3 = 5200; hA2A/hA3 = 7200), in comparison to the C2-furyl counterpart. A receptor-driven molecular modeling investigation, based on a recently proposed model of A 3 receptor derived from the crystallographic structure of human A2A receptor, has been carried out in order to support the experimental binding data and to justify the enhanced selectivity against the other receptor subtypes.