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Arylimidamides (AIAs), previously termed as reversed amidines, present a broad spectrum of activity against intracellular microorganisms. In the present study, three novel AIAs were evaluated in a mouse model of Trypanosoma cruzi infection, which is the causative agent of Chagas disease. The bis-AIAs DB1957, DB1959 and DB1890 were chosen based on a previous screening of their scaffolds that revealed a very promising trypanocidal effect at nanomolar range against both the bloodstream trypomastigotes (BTs) and the intracellular forms of the parasite. This study focused on both mesylate salts DB1957 and DB1959 besides the hydrochloride salt DB1890. Our current data validate the high activity of these bis-AIA scaffolds that exhibited EC50 (drug concentration that reduces 50% of the number of the treated parasites) values ranging from 14 to 78 nM and 190 to 1,090 nM against bloodstream and intracellular forms, respectively, also presenting reasonable selectivity indexes and no mutagenicity profile predicted by in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET). Acute toxicity studies using murine models revealed that these AIAs presented only mild toxic effects such as reversible abdominal contractions and ruffled fur. Efficacy assays performed with Swiss mice infected with the Y strain revealed that the administration of DB1957 for 5 consecutive days, with the first dose given at parasitemia onset, reduced the number of BTs at the peak, ranging between 21 and 31% of decrease. DB1957 was able to provide 100% of animal survival, while untreated animals showed 70% of mortality rates. DB1959 and DB1890B did not reduce circulating parasitism but yielded >80% of survival rates.

The synthesis of four new benzyloxybromobenzonitriles including: 2‐benzyloxy‐4‐bromobenzonitrile (3), 3‐benzyloxy‐4‐bromobenzonitrile (7), 5‐benzyloxy‐2‐bromobenzonitrile (11) and 3‐benzyloxy‐2‐bromobenzonitrile (12) is reported.

The use of phosphorus trichloride for synthesis of 3-alkoxy, 3-aryloxy and 3-substitutedamino-2,5-diarylfurans from α,β-unsaturated-1,4-diketones by reductive-furanization is reported.

Natural abundance 17O NMR data for 14 substituted methyl N-arylcarbamates obtained in acetonitrile solution at 75°C are reported. The 17O NMR chemical shifts of hindered ortho N-arylcarbamates are shielded relative to unhindered ones; a quantitative relationship is observed between the carbonyl 17O NMR chemical shifts and molecular mechanics (MM2) predicted torsion angles. The carbonyl 17O NMR chemical shifts of meta and para substituted N-arylcarbamates are correlated with Hammett sigma constants.

Natural abundance 17O NMR chemical shift data for meta- and para-substitued α,α,α-trifluoromethoxybenzenes recorded in acetonitrile at 75° C are reported. The 17O NMR signals for the trifluoromethoxy compounds are deshielded by greater than 65 ppm compared to analogous methoxy compounds. A quantitative relationship between 17O NMR chemical shifts for the trifluoromethoxy and methoxy benzenes is reported.

Natural abundance 17O NMR chemical shift data for 12 variably hindered aryl acid chlorides recorded in acetonitrile at 75° C are reported. The 17O NMR signals for the hindered acid chlorides are deshielded relative to unhindered isomers. A quantitative relationship between molecular mechanics (MM2) estimated torsion angles and 17O NMR chemical shifts for the aryl acid chlorides is developed.

Natural abundance 17O NMR data for a series of thiol esters and related analogs are reported. The carbonyl signal of the thiol esters range from 463 ppm to 514 ppm; these values are downfield of their oxygen analogs by ca. 150 ppm. A linear relationship between the 17O NMR chemical shift of the thio-compounds and their oxo-analogs is observed.

The natural abundance 170 nmr spectra of seventeen aryl isocyanates are reported. Electronic effects of substituents are consistent with previously investigated carbonyl containing functional groups; however, the steric effects of ortho-alky 1 groups give results which are opposite to those noted for other systems.

α,β-Unsaturated nitriles are selectively reduced, in good yields, to their saturated analogs by sodium borohydride in a methanol-pyridine solvent system.