934524-68-2

Upstream product

• 515880-06-5 4-(N-methyl-N-phenylamino)-2-propylpyrazolo[1,5-a]-1,3,5-triazine 
• 934524-67-1 2-n-propyl-3H-pyrazolo[1,5-a][1,3,5]triazin-4-one 
• 100-61-8 N-methylaniline 

Downstream Products

• 1029530-84-4 8-[(hydroxy)(phenyl)methyl]-4-(N-methyl-N-phenylamino)-2-n-propylpyrazolo[1,5-a]-1,3,5-triazine 
• 1029530-88-8 8-[(hydroxy)(2-methoxyphenyl)methyl]-4-(N-methyl-N-phenylamino)-2-n-propylpyrazolo[1,5-a]-1,3,5-triazine 

Relevant academic research and scientific papers

Cyclic nucleotide phosphodiesterase type 4 inhibitors: Evaluation of pyrazolo[1,5-a]-1,3,5-triazine ring system as an adenine bioisostere

A series of 8-substituted pyrazolo[1,5-a]-1,3,5-triazines were considered as a bioisosteric replacement for the 9-substituted adenine derivatives resulting in the discovery of 8-(2-methoxybenzyl)-4-(N-methylamino)-2-n-propylpyrazolo[1,5-a]-1,3,5-triazine (14d) and 2-trifluoromethyl-8-(2-methoxybenzyl)-4-(N-methylamino)pyrazolo[1,5-a]-1,3,5-triazine (14e) as a new structural class of potent phosphodiesterase type 4 inhibitors (IC50 = 13 nM and 11 nM, respectively) with high isoenzyme selectivity. An original tandem of reactions involving a palladium-mediated cross-coupling reaction (PMCCR) of the readily available 8-iodo-2-methyl-4-(N-methyl-N-phenylamino)pyrazolo[1,5-a]-1,3,5-triazine (11a) and arylboronic acids or alkynes followed by the displacement of the N-methyl-N-phenylamino group constitute the key steps in a novel synthetic approach developed herein. The treatment of 11a-c with n-BuLi and selected aldehydes represents an interesting alternative to the PMCCR for the synthesis of benzylic derivatives 14a-i. Preliminary biological testing has shown that compounds 14d and 14e strongly inhibit LPS-induced TNFα release from human mononuclear cells from healthy subjects. These two compounds were selected for further biological evaluation.

Synthesis of 8-substituted pyrazolo[1,5-a]-1,3,5-triazine derivatives by palladium-catalyzed cross-coupling reactions

8-Substituted pyrazolo[1,5-a]-1,3,5-triazine derivatives 6 were prepared from the corresponding 8-iodopyrazolo[1,5-a]-1,3,5-triazines 5 through palladium-catalyzed cross-coupling reactions. Several bioisosteres of hypoxanthine drugs 2 were then prepared b