339365-49-0

Upstream product

• 56366-92-8 N-hydroxy-3-(hydroxylamino)-3-iminopropanamide 
• 123-54-6 acetylacetone 

Downstream Products

• 56366-95-1 1-benzoyl-4,6-dimethylisoxazolo[3,4-b]pyridin-3(1H)-one 

Relevant academic research and scientific papers

Lipophilicity determination of antifungal isoxazolo[3,4-b]pyridin-3(1h)-ones and their n1-substituted derivatives with chromatographic and computational methods

The lipophilicity of a molecule is a well-recognized as a crucial physicochemical factor that conditions the biological activity of a drug candidate. This study was aimed to evaluate the lipophilicity of isoxazolo[3,4-b]pyridine-3(1H)-ones and their N1-substituted derivatives, which demonstrated pronounced antifungal activities. Several methods, including reversed-phase thin layer chromatography (RP-TLC), reversed phase high-performance liquid chromatography (RP-HPLC), and micellar electrokinetic chromatography (MEKC), were employed. Furthermore, the calculated logP values were estimated using various freely and commercially available software packages and online platforms, as well as density functional theory computations (DFT). Similarities and dissimilarities between the determined lipophilicity indices were assessed using several chemometric approaches. Principal component analysis (PCA) indicated that other features beside lipophilicity affect antifungal activities of the investigated derivatives. Quantitative-structure-retention-relationship (QSRR) analysis by means of genetic algorithm - partial least squares (GA-PLS) - was implemented to rationalize the link between the physicochemical descriptors and lipophilicity. Among the studied compounds, structure 16 should be considered as the best starting structure for further studies, since it demonstrated the lowest lipophilic character within the series while retaining biological activity. Sum of ranking differences (SRD) analysis indicated that the chromatographic approach, regardless of the technique employed, should be considered as the best approach for lipophilicity assessment of isoxazolones.

Synthesis and biological evaluation of hybrid quinolone-based quaternary ammonium antibacterial agents

A series of novel fluoroquinolone-Safirinium dye hybrids was synthesized by means of tandem Mannich-electrophilic amination reactions from profluorophoric isoxazolones and antibiotics bearing a secondary amino group at position 7 of the quinoline ring. The obtained fluorescent spiro fused conjugates incorporating quaternary nitrogen atoms were characterized by 1H NMR, IR, MS, and elemental analysis. All the synthetic analogues (3a-h and 4a-h) were evaluated for their in vitro antimicrobial, bactericidal, and antibiofilm activities against a panel of Gram positive and Gram-negative pathogenic bacteria. The most active Safirinium Q derivatives of lomefloxacin (4d) and ciprofloxacin (4e) exhibited molar-based antibacterial activities comparable to the unmodified drugs and displayed considerable inhibitory potencies in E. coli DNA gyrase supercoiling assays with IC50 values in the low micromolar range. Zwiterionic hybrids were noticeably less lipophilic than the parent quinolones in micellar electrokinetic chromatography (MECK) experiments. The tests performed in the presence of phenylalanine-arginine β-naphthylamide (PAβN) or carbonyl cyanide m-chlorophenylhydrazone (CCCP) revealed that the conjugates are to some extent subject to bacterial efflux and cellular accumulation, respectively. Moreover, the hybrids did not exhibit notable cytotoxicity towards the HEK 293 control cell line and demonstrated low propensity for resistance development, as exemplified for compounds 3g and 4b. Finally, molecular docking experiments revealed that the synthesized compounds were able to bind in the fluoroquinolone-binding mode at S. aureus DNA gyrase and S. pneumoniae topoisomerase IV active sites.

The tandem mannich-electrophilic amination reaction: A versatile platform for fluorescent probing and labeling

Tandem fluorogenic reaction: A new platform for the direct, selective and sensitive detection of formaldehyde and/or secondary aliphatic amines, based on a tandem Mannich-electrophilic amination reaction, is described. Biological applications of hydrophilic, water-soluble fluorescent 2,2-dialkyl-2,3-dihydro- [1,2,4]triazolo[4,3-a]pyridin-2-ium-8-carboxylates (Safarinium P probes) are exemplified by labeling of the amine-containing Ac-AKF-NH2 peptide and Bacillus subtilis spores in aqueous solution. Copyright

New derivatives of 4,6-dimethylisoxazolo[3,4-b] pyridin-3(1H)-one: Synthesis, tautomerism, electronic structure and antibacterial activity

The electronic structure and prototropic tautomerism of 4,6-dimethylisoxazolo[3,4-b]pyridin-3(1H)-one (1) were studied theoretically with use of the B3LYP/6-31Gand ωB97X-D/6-31Gdensity functional methods and SM8 (H2O, DMF) solvation models. Compound 1, which is a weak acid with a pKa of 6.9, undergoes regioselective alkylation and sulfonylation under basic reaction conditions to give a series of N1-substituted products 2a-i. Later compounds were evaluated in vitro for antibacterial activity with the use of 68 strains of aerobic and anaerobic bacteria, including 12 reference strains.

Cytotoxic triterpenoid–safirinium conjugates target the endoplasmic reticulum

Safirinium P and Q fluorescence labels were synthesized and conjugated with spacered triterpenoic acids to access hybrid structures. While the parent safirinium compounds were not cytotoxic at all, many triterpenoid safirinium P and Q conjugates showed moderate cytotoxicity. An exception, however, was safirinium P derived compound 30 holding low EC50 = 5.4 μM (for A375 cells) to EC50 = 7.5 μM (for FaDu cells) as well as EC50 = 6.6 μM for non-malignant fibroblasts NIH 3T3. Fluorescence imaging showed that the safirinium core structures cannot enter the cells (not even after a prolonged incubation time of 24 h), while the conjugates (as exemplified for 30) are accumulating in the endoplasmic reticulum but not in the mitochondria. The development of safirinium–hybrids targeting the endoplasmic reticulum can be regarded as a promising strategy in the development of cytotoxic agents.

Synthesis and antifungal activity of some 4,6-dimethylisoxazolo[3,4-b]pyridin-3(1H)-one derivatives

Background: Cutaneous and invasive fungal infections are constant threats to human health that substantiate the-need for the development of new efficacious and safe antimycotics. Methods: A series of N1-alkyl, N1-acyl and N1-sulfonyl derivatives of 4,6-dimethylisoxazolo[3,4-b]pyridin-3(1H)-one (1) were synthesized. The antimicrobial activities of title compounds against 21 pathogenic yeast-like fungal clinical isolates and 5 reference strains were evaluated by means of a broth microdilution method. Results: Among the compounds tested, the newly prepared N1-benzoyl (2m) and N1-(4-fluorobenzoyl) (2n) derivatives of 1 showed 81% and 95% inhibitory efficacy, respectively, against the clinical isolates, which were comparable to that of the reference drug fluconazole. The strains that exhibited the highest susceptibility to the compound 2n included Candida utilis (MIC 6.2 μg/mL), C. parapsilosis (MIC in the range 6.2 -12.5 μg/mL), Geotrichum candidum (MIC = 12.5 μg/mL) as well as C. lusitaniae and Rhodotorula mucilaginosa (MIC = 25 μg/mL). Conclusion: In terms of MIC, compound 2n proved to be four times more active against the clinical isolates of Candida albicans and C. albicans ATCC 10231 standard strain than fluconazole, the widely prescribed antifungal agent for mucosal and systemic yeast infections (MIC = 50 vs 200 μg/mL).