Cyclocondensation of 6‐acetyl‐4,7‐dihydro‐5‐methyl‐7‐phenyl[1,2,4]triazolo[1,5‐a]pyrimidine with hydroxylamine and hydrazine

Abstract

The cyclocondensation of 6‐acetyl‐4,7‐dihydro‐5‐methyl‐7‐phenyl[1,2,4]triazolo[1,5‐a]pyrimidine (3) with hydroxylamine or hydrazine leads to 3a,4,9,9a‐tetrahydro‐3,9a‐dimethyl‐4‐phenylisoxazolo‐[5,4‐d][1,2,4]triazolo[1,5‐a]pyrimidine (4a) and 3a,4,9,9a‐tetrahydro‐3,9a‐dimethyl‐4‐phenyl‐1H‐pyrazolo[3,4‐d][1,2,4]triazolo[1,5‐a]pyrimidine (4b), respectively. In the presence of methanolic hydrogen chloride, 4b undergoes a cleavage of the pyrimidine ring to yield (5‐amino‐1,2,4‐triazol‐1‐yl)(3,5‐dimethylpyrazol‐4‐yl)phenylmethane (5). The structure determination of the compounds obtained is based on 1H and 13C nmr spectra including NOE measurements.

Synthesis of pyrazolo[4,3-e][1,2,4]triazine sulfonamides, novel Sildenafil analogs with tyrosinase inhibitory activity

“…13 Moreover, this system, for example, pyrazolo [4,3-e] [1,2,4]triazine is structurally related to pyrazolo [4,3-d]pyrimidin-7-one present in the structure of Sildenafil and its methyl ether analogs which were found to show tyrosinase inhibitory effect, apart from its well-known orally effective properties for the treatment of male erectile dysfunction. 14,15 It should be noted that so far no analogs of Sildenafil containing the skeleton of 1H-pyrazolo [4,3-e] [1,2,4]triazine ring system have been described in the literature. With regard to the above discussed facts, we envisage a high potential of the pyrazolo [4,3-e] [1,2,4]triazine system regarding the discovery of new biological activities.…”

“…Despite the fact that pyrazolo [4,3-e] [1,2,4]triazines have been less studied in the group of condensed pyrazolotriazines, some of them show moderate inhibition of purine nucleoside phosphorylase 11 and cytotoxic activity in A549 lung carcinoma cell line at submicromolar range, 12 induction of caspase-dependent cell death, and inhibition of cyclin-dependent kinase 2 (CDK2). 13 Moreover, this system, for example, pyrazolo [4,3-e] [1,2,4]triazine is structurally related to pyrazolo [4,3-d]pyrimidin-7-one present in the structure of Sildenafil and its methyl ether analogs which were found to show tyrosinase inhibitory effect, apart from its well-known orally effective properties for the treatment of male erectile dysfunction. 14,15 It should be noted that so far no analogs of Sildenafil containing the skeleton of 1H-pyrazolo [4,3-e] [1,2,4]triazine ring system have been described in the literature.…”

“…[1][2][3] Furthermore, the multiple biological activities of pyrazole and its annelated derivatives are of increasing interest as antimycotics, 4 antidepressants, 5 fungicidal 6 or herbicidal agents. 7 Compounds containing the pyrazolo [4,3-e] [1,2,4]triazine moiety have attracted considerable attention due to their anticancer and antibacterial activity.…”

“…[1][2][3] Furthermore, the multiple biological activities of pyrazole and its annelated derivatives are of increasing interest as antimycotics, 4 antidepressants, 5 fungicidal 6 or herbicidal agents. 7 Compounds containing the pyrazolo [4,3-e] [1,2,4]triazine moiety have attracted considerable attention due to their anticancer and antibacterial activity. [8][9][10] The most important members in this family of naturally occurring purine analogs are pseudoiodinine, 8 nostocine A 9 and fluviols A-E 10 produced by Pseudomona fluorescens var.…”

Synthesis of new pyrazolo[1,5‐a]pyrimidines and pyrazolo[3,4‐b]pyridines

“…Azoloazines are biologically interesting molecules and their chemistry is now receiving considerable attention [1][2][3]. One of the major routes to azoloazines is the reaction of α,β-unsaturated ketones, and/or nitriles with azolylamine derivatives [4,5].…”