54968-77-3Relevant academic research and scientific papers
Synthesis, characterization and anti-proliferation activities of novel cyano oximino sulfonate esters
El-Faham, Ayman,Elnakdy, Yasser Abbas,El Gazzar, Sarah Abdou Mohamed,El-Rahman, Mohamed Mokbel Abd,Khattab, Sherine Nabil
, p. 373 - 378 (2014)
A series of novel cyano oximino sulfonate derivatives were prepared from the reaction of arylsulfonyl chloride with different cyanoacetamide-based oximes ranging from the simplest unsubstituted amide to analogues containing N-ethyl (mimicking the Oxyma template), N-piperidinyl and N-morpholinyl chains. In addition, the cyano oximes, N-hydroxybenzimidoyl cyanide and N-hydroxypicolinimidoyl cyanide were also used in the synthesis of the novel cyano oximino sulfonate derivatives. The structures of the prepared compounds were confirmed by 1H-NMR, 13C-NMR, and elemental analysis. The preliminary bioassays showed that some of the title compounds, such as 2-oxo-2-(piperidin-1-yl)-N-(tosyloxy)acetimidoyl cyanide (TsPipOx), N-(tosyloxy)benzimidoyl cyanide (TsPhOX), N-(naphthalen-2-ylsulfonyloxy)-2-oxo- 2-(piperidin-1-yl)acetimidoyl cyanide (NpsPipOx), 2-amino-N-(naphthalen-2- ylsulfonyloxy)-2-oxoacetimidoyl cyanide (NpsAmOx), N-(naphthalen-2- ylsulfonyloxy)benzimidoyl cyanide (NpsPhCN), and N-(naphthalen-2-ylsulfonyloxy) picolinimidoyl cyanide (NpsPyCN), showed anti-proliferation effect on the mouse fibroblast L929. The calculated IC50-values were ranging between 36.5 μg/mL and 0.235 mg/mL. However the anti-proliferation effects seem to be cytostatic rather than cytotoxic. The compounds only minimize the growth activity without completely killing the cells.
Design, synthesis and biological evaluation of novel Pseudomonas aeruginosa DNA gyrase B inhibitors
Balraju, Vadla,Jogula, Sridhar,Krishna, Vagolu Siva,Meda, Nikhila,Sriram, Dharmarajan
, (2020/05/08)
In the present study, we attempted to develop a novel class of compounds active against Pseudomonas aeruginosa (Pa) by exploring the pharmaceutically well exploited enzyme targets. Since, lack of Pa gyrase B crystal structures, Thermus thermophilus gyrase B in complex with novobiocin (1KIJ) was used as template to generate model structure by performing homology modeling. Further the best model was validated and used for high-throughput virtual screening, docking and dynamics simulations using the in-house database for identification of Pa DNA gyrase B inhibitors. This study led to an identification of three lead molecules with IC50 values in range of 6.25–15.6 μM against Pa gyrase supercoiling assay. Lead-1 optimization and expansion resulted in 15 compounds. Among the synthesized compounds six compounds were shown good enzyme inhibition than Lead-1 (IC50 6.25 μM). Compound 13 emerged as the most potential compound exhibiting inhibition of Pa gyrase supercoiling with an IC50 of 2.2 μM; and in-vitro Pa activity with MIC of 8 μg/mL in presence of efflux pump inhibitor; hence could be further developed as novel inhibitor for Pa gyrase B.
SUBSTITUTED IMIDAZO[1,2-b]PYRIDAZINES, SUBSTITUTED IMIDAZO[1,5-b]PYRIDAZINES, RELATED COMPOUNDS, AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS
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Paragraph 00391, (2017/12/14)
The invention provides substituted imidazo[1,2-b]pyridazine compounds, substituted imidazo[1,5-b]pyridazine compounds, related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted imidazo[1,2-b]pyridazine compounds described herein include substituted imidazo[1,2-b]pyridazine-3-carboxamide compounds and variants thereof.
