87539-99-9Relevant academic research and scientific papers
Anticancer potential of new 3-nitroaryl-6-(N-methyl)piperazin-1,2,4-triazolo[3,4-a]phthalazines targeting voltage-gated K+ channel: Copper-catalyzed one-pot synthesis from 4-chloro-1-phthalazinyl-arylhydrazones
Arvelo, Francisco,Morales, Alvaro,Romero, Angel H.,Sojo, Felipe,Calderón, Christian,López, Simón E.
, (2020)
A series of six 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines were prepared through a facile and efficient one-pot copper-catalyzed procedure from 4-chloro-1-phthalazinyl-arylhydrazones with relatively good yields (62–83percent). The one-pot copper-catalytic procedure consists of two simultaneous reactions: (i) a direct intramolecular dehydrogentaive cyclization between ylidenic carbon and adjacent pyrazine nitrogen to form 1,2,4-triazolo ring and, (ii) a direct N-amination on carbon-chlorine bond. Then, an in vitro anticancer evaluation was performed for the synthesized compounds against five selected human cancer cells (A549, MCF-7, SKBr3, PC-3 and HeLa). The nitro-derivatives were significantly more active against cancer strains than against the rest of tested compounds. Specifically, compound 8d was identified as the most promising anticancer agent with significant biological responses and low relative toxicities on human dermis fibroblast. The cytotoxic effect of compound 8d was more significant on PC3, MCF-7 and SKBr3 cancer cells with low-micromolar IC50 value ranging from 0.11 to 0.59 μM, superior to Adriamycin drug. Mechanistic experimental and theoretical studies demonstrated that compounds 8d act as a K+ channel inhibitor in cancer models. Further molecular docking studies suggest that the EGFR Tyrosine Kinase enzyme may be a potential target for the most active 3-aryl-6-(N-methylpiperazin)-1,2,4-triazolo[3,4-a]phthalazines.
Optimization of phthalazin-based aryl/heteroarylhydrazones to design new promising antileishmanicidal agents: Synthesis and biological evaluation of 3-aryl-6-piperazin-1,2,4-triazolo[3,4-a] phthalazines
Ramírez, Oscar G.,Rodríguez, Noris,Romero, Angel H.
, p. 13807 - 13814 (2020)
1-Monosubstituted and 1,4-substituted phthalazins based on aryl/heteroarylhydrazinyl have demonstrated attractive antileishmanial profiles against amastigote forms of the Leishmania braziliensis parasite. Further optimization of the mentioned acyclic scaffold motivated us to design a series of 3-aryl-1,2,4-triazolo[3,4-a]phthalazines, cyclic versions of the phthalazins based on aryl/heteroarylhydrazinyl, which have not been evaluated against Leishmania parasites yet. In order to compare to phthalazine-based aryl/heteroarylhydrazones, five essential 3-aryl-6-piperazin-1,2,4-triazolo[3,4-a]phthalazines were efficiently prepared in excellent yields (73-83%) through a facile one-pot procedure from 4-chloro-1-phthalazinyl-arylhydrazones via C-H dehydrogenative cyclization using silver(i) salt. From in vitro antileismanial evaluation, compound 2d, a nitro derivative, was identified as the most promising agent with a good anti-amastigote response (IC50 = 9.37 μM) and low relative toxicity against peritoneal macrophages (LD50 = 123.93 μM). A moderate response was found against clinical amastigote isolates of L. braziliensis, although superior compared to the reference glucantime. A comparison with their phthalazin analogues based on aryl/heteroarylhydrazinyl gave evidence that the efficacy of each chemical system is determined by the nature of the functionalization next to the aryl moiety, which suggests that different mechanisms of action are involved for each chemical system. The cyclized form led to an enhancement of the antileismanial activity compared to the acyclic form, but the nitroderivatives seemed to be highly more toxic than the parent non-cyclized compounds. From the three compared phthalazine groups, 4-chloro-1-phthalazine-(5-nitrofuryl)hydrazinil with a nanomolar antileishmanial response was identified as a promising lead for further optimization, whereas compound 2d emerges as a prominent hit platform to prepare a group of derivatives based on phthalazine-1,2,4-triazolo bearing 3-nitro-phenyl at the 3-position. This journal is
6-(Alkylamino)-3-aryl-1,2,4-triazolophthalazines. A New Class of Benzodiazepine Receptor Ligands
Tarzia, Giorgio,Occelli, Emilio,Toja, Emilio,Barone, Domenico,Corsico, Nerina,et al.
, p. 1115 - 1123 (2007/10/02)
Some 6-(alkylamino)-3-aryl-1,2,4-triazolophthalazines have been shown to displace diazepam from rat brain specific binding sites, in vitro, with Ki (nM) values comparable to those of reference benzodiazepines and to have anticonvulsant (
