Synthesis and cytotoxic activity evaluation of some novel 1-(3-(aryl-4,5-dihydroisoxazol-5-yl)methyl)-4-trihalomethyl-1 H -pyrimidin-2-ones in human cancer cells

Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

“…The 1,3-dipolar cycloaddition reactions between allylated pyrazoles 4a – d and nitrile oxides 5a – e , resulted in a single regioisomer 6 in the absence of any trace of the regioisomer 6′ (Scheme ). This result is in perfect agreement with literature data on the regiochemistry of the 1,3-dipolar cycloaddition of nitrile oxides with allyl compounds controlled by both steric and electronic factors. − The regiochemistry of the obtained isoxazolines 6a – m is proposed on the basis of the chemical shifts of the protons (H 4 and H 5 ) and carbons (C 4 and C 5 ) of the isoxazolinic ring with reference to the analogous compounds (Figure ). − …”

“…Indeed, the 1 H NMR spectrum of hybrid compound 6a show the existence of a multiplet between 4.98 and 5.07 ppm corresponding to the proton of the methine group (C H 5 ) of the stereogenic center of the isoxazoline ring. This resulting chemical shift value agrees with the chemical shift of the proton H 5 of the 3,5-disubstituted isoxazoline regioisomer. − The two diastereotopic hydrogen atoms linked to the methylene groups adjacent to the stereogenic center of the isoxazoline ring C 4 H A H M resonate as two doublet-of-doublets at 3.15 ppm ( J = 7.3, 16.69 Hz) and 3.43 ppm ( J = 10.47, 16.69 Hz), and forms an AB system due to geminal and vicinal proton–proton coupling (Figure ). The chemical shift values of protons H 5 and H 4 in the isoxazoline ring confirm the formation of 3,5-disubstituted isoxazoline as a single regioisomer. − It also shows the presence of a multiplet signal between 3.50 and 3.57 ppm attributable to the two methylene protons linked to the nitrogen atom (C H 2 –N), and a triplet signal located at 8.99 ppm corresponds to the proton of −NH group.…”

Novel quinazolinone-isoxazoline hybrids: synthesis, structural elucidation and theoretical DFT mechanistic study

“…3). The chemical shift value of the H 5 proton of the isoxazoline ring is in good agreement with that found in the literature [28, 53,54]. The singlet signal at 8.17 ppm attributed to the proton of methine group (= CH-) attached to the two nitrogen atoms of quinazolin-4(3H)-one.…”

“…S7) shows the presence of three signals located at 37.88 ppm, 78.63 ppm, and 156.19 ppm attributed the carbons of the methylene (CH 2 ), methine (CH), and imine (C = N) groups of the isoxazoline nucleus, respectively. These obtained chemical shift values are in good agreement with the literature, and con rm the formation of a single regioisomer namely 3,5-disubstituted isoxazoline [28,53,54]. Other signals located at 146.90 ppm and 161.48 ppm are assigned to the methine (N = CH-N) and ketone (C = O) carbons of quinazolin-4(3H)-one, respectively.…”

“…The signal at 49.16 ppm correspond to the methylene spacer carbon (CH 2 ) that links isoxazoline ring with quinazolin-4(3H)one. The obtained 13C NMR data for compound 4a are in perfect agreement with the 3,5-disubstituted isoxazoline regioisomer [28,53,54]. Moreover, the homonuclear ( 1 H-1 H) and heteronuclear ( 1 H-13 C) 2D NMR spectra of compound 4a con rm unambiguously the assignment of the different signals made on the 1D NMR spectra ( 1 H and 13 C).…”