151291-05-3Relevant articles and documents
Design, synthesis, and biological evaluation of C9- and C2-substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists
Baraldi, Pier Giovanni,Fruttarolo, Francesca,Tabrizi, Mojgan Aghazadeh,Preti, Delia,Romagnoli, Romeo,El-Kashef, Hussein,Moorman, Allan,Varani, Katia,Gessi, Stefania,Merighi, Stefania,Borea, Pier Andrea
, p. 1229 - 1241 (2007/10/03)
In the past few years, our group has been involved in the development of A2A and A3 adenosine receptor antagonists which led to the synthesis of SCH58261 (5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo [1,5-c]pyrimidine, 61), potent and very selective at the A2A receptor subtype, and N8-substituted-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidines-N5-urea or amide (MRE series, b), very selective at the human A3 adenosine receptor subtype. We now describe a large series of C9- and C2-substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines to represent an extension of structure-activity relationship work on this class of tricyclic compounds. The introduction of a substituent at 9 position of the tricyclic antagonistic structure led to retention of receptor affinity but a loss of selectivity in respect to the lead compounds b, N8-substituted-pirazolo[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidines-N5-urea or -amide. The substitution of the furanyl moiety of compound 61, necessary for receptor binding, with a phenyl or a substituted aromatic ring (compounds 5a-d, 6-8), caused a complete loss of the affinity at all the adenosine receptor subtypes, demonstrating that the furanyl ring is a necessary structural element to guarantee interaction with the adenosine receptor surface. The introduction of an ethoxy group at the ortho position of the aromatic ring to mimic the oxygen of the furan (compound 5c, 5-amino-7-(2-phenylethyl)-2-(2-ethoxyphenyl)pyrazolo[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine) did not enhance affinity. The introduction of the cycloaminomethyl function by Mannich reaction at the 5′ position of the furanyl ring of 61 and the C9-substituted compound 41 (5-amino-8-methyl-9-methylsulfanyl-2-(2-furyl)-pyrazolo[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine) resulted in complete water solubility but a loss of receptor affinity. We can conclude that modifications or substitutions at the furanyl ring are not allowed and the introduction of a substituent at the 9-position of the core pyrazolo-triazolo-pyrimidine structure caused a severe loss of selectivity, probably due to an increased steric hindrance of the radical introduced.
1-Methyl-5-alkylsulfonyl-, 1-methyl-5-alkylsulfinyl- and 1-methyl-5-alkylthio- substituted pyrazolylpyrazoles, processes for their preparation and their use as herbicides
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, (2008/06/13)
1-Methyl-5-alkylsulfonyl-, 1-methyl-5-alkylsulfinyl- and 1-methyl-5-alkylthio-substituted pyrazolylpyrazoles, processes for their preparation and their use as herbicides 1 -Methyl-5-alkylsulfonyl-, 1-methyl-5-alkylsulfinyl- and 1-methyl-alkylthio-substitu
Synthesis of Pyrrazoles and Pyrazolopyrimidines from 3-Arylsulfonylaminoacrylates
McFadden, Helen G.,Huppatz, John L.,Halladay, Peter K.
, p. 873 - 886 (2007/10/02)
3-Arylsulfonylaminopyrazole-4-carboxamides and -carboxylates were synthesized from 3-arylsulfonylamino-3-methylthiocyanoacrylate derivatives as potential herbicidal inhibitors of the enzyme acetohydroxyacetic acid synthase (AHAS). Some of these compounds
