《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》 was written by Romero, Angel H.; Rodriguez, Noris; Ramirez, Oscar G.. Computed Properties of C5H12N2 And the article was included in New Journal of Chemistry in 2020. The article conveys some information:
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 clin. amastigote isolates of L. braziliensis, although superior compared to the reference glucantime. A comparison with their phthalazin analogs based on aryl/heteroarylhydrazinyl gave evidence that the efficacy of each chem. 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 chem. 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-Ph at the 3-position. The results came from multiple reactions, including the reaction of 1-Methylpiperazine(cas: 109-01-3Computed Properties of C5H12N2)
1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..Computed Properties of C5H12N2
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics