1350554-98-1Relevant academic research and scientific papers
A Convenient Synthesis of Pyrazole-imidazoline Derivatives by Microwave Irradiation
de S. Rosa, Getúlio,Souto, Bernardo A.,Pereira, Cynthia N.,Teixeira, Bruna C.,dos Santos, Maurício S.
, p. 1825 - 1830 (2019/04/30)
A series of 28 hybrids pyrazole-imidazolines 1a–n and 2a–n were synthesized by a new methodology using microwave irradiation, in short time (20–30?min), in low power (50–70?W), and in 34–92% yield. Among all methodologies evaluated, no side products were obtained. All derivatives were completely characterized by FT–IR, 1H and 13C NMR, GC–MS, and HRMS.
Synthesis, structure-activity relationship and trypanocidal activity of pyrazole-imidazoline and new pyrazole-tetrahydropyrimidine hybrids as promising chemotherapeutic agents for Chagas disease
Monteiro,Lechuga,Lara,Souto,Viganó,Bourguignon,Calvet,Oliveira,Alves,Souza-Silva,Santos,Pereira
, (2019/08/20)
Drug therapy for Chagas disease remains a major challenge as potential candidate drugs have failed clinical trials. Currently available drugs have limited efficacy and induce serious side effects. Thus, the discovery of new drugs is urgently needed in the fight against Chagas' disease. Here, we synthesized and evaluated the biological effect of pyrazole-imidazoline (1a-i) and pyrazole-tetrahydropyrimidine (2a-i) derivatives against relevant clinical forms of Trypanosoma cruzi. The structure-activity relationship (SAR), drug-target search, physicochemical and ADMET properties of the major active compounds in vitro were also assessed in silico. Pyrazole derivatives showed no toxicity in Vero cells and also no cardiotoxicity. Phenotypic screening revealed two dichlorinated pyrazole-imidazoline derivatives (1c and 1d) with trypanocidal activity higher than that of benznidazole (Bz) against trypomastigotes; these were also the most potent compounds against intracellular amastigotes. Replacement of imidazoline with tetrahydropyrimidine in the pyrazole compounds completely abolished the trypanocidal activity of series 2(a-i) derivatives. The physicochemical and ADMET properties of the compounds predicted good permeability, good oral bioavailability, no toxicity and mutagenicity of 1c and 1d. Pyrazole nucleus had high frequency hits for cruzipain in drug-target search and structure activity relationship (SAR) analysis of pyrazole-imidazoline derivatives revealed enhanced activity when chlorine atom was inserted in meta-positions of the benzene ring. Additionally, we found evidence that both compounds (1c and 1d) have the potential to interact non-covalently with the active site of cruzipain and also inhibit the cysteine proteinase activity of T. cruzi. Collectively, the data presented here reveal pyrazole derivatives with promise for further optimization in the therapy of Chagas disease.
Synthesis and antileishmanial evaluation of 1-aryl-4-(4,5-dihydro-1H- imidazol-2-yl)-1H-pyrazole derivatives
Dos Santos, Mauricio S.,Oliveira, Mariana L.V.,Bernardino, Alice M.R.,De Leo, Rosa M.,Amaral, Veronica F.,De Carvalho, Flavia T.,Leon, Leonor L.,Canto-Cavalheiro, Marilene M.
supporting information; scheme or table, p. 7451 - 7454 (2012/02/03)
A series of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (4a-g) and 5-amino-1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (5a-g) were synthesized and evaluated in vitro against three Leishmania species: L. amazonensis, L. braziliensis and L. infantum (L. chagasi syn.). The cytotoxicity was assessed. Among the derivatives examined, six compounds emerged as the most active on promastigotes forms of L. amazonensis with IC50 values ranging from 15 to 60 μM. The reference drug pentamidine presented IC 50 = 10 μM. However, these new compounds were less cytotoxic than pentamidine. Based on these results, the more promising derivative 5d was tested further in vivo. This compound showed inhibition of the progression of cutaneous lesions in CBA mice infected with L. amazonensis relative to an untreated control.
