515880-06-5Relevant academic research and scientific papers
Synthesis of 8-substituted pyrazolo[1,5-a]-1,3,5-triazine derivatives by palladium-catalyzed cross-coupling reactions
Popowycz, Florence,Bernard, Philippe,Raboisson, Pierre,Joseph, Benoit
, p. 367 - 374 (2007)
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
Cyclic nucleotide phosphodiesterase type 4 inhibitors: Evaluation of pyrazolo[1,5-a]-1,3,5-triazine ring system as an adenine bioisostere
Raboisson, Pierre,Schultz, Dominique,Muller, Christian,Reimund, Jean-Marie,Pinna, Guillaume,Mathieu, Romain,Bernard, Philippe,Do, Quoc-Tuan,DesJarlais, Renee L.,Justiano, Helene,Lugnier, Claire,Bourguignon, Jean-Jacques
, p. 816 - 829 (2008/09/20)
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.
Efficient synthesis of 8-substituted pyrazolo[1,5-a]-1,3,5-triazines by regioselective acylation
Raboisson, Pierre,Schultz, Dominique,Lugnier, Claire,Bourguignon, Jean-Jacques
, p. 9501 - 9503 (2007/10/03)
An efficient two-step synthesis of 8-acylated pyrazolo[1,5-a]-1,3,5-triazines has been accomplished. The key strategic elements of this novel synthetic approach involve the use of the N-methyl-N-phenylamino activating group, which was easily obtained in high yield by treatment of the pyrazolotriazin-4-one with phosphorus oxychloride and dimethylaniline through high pressure reaction coupled with a regioselective acylation at position 8 followed by the subsequent displacement of the N-methyl-N-phenylamino group upon treatment with various amines.
