Crystal structure and Hirshfeld surface analysis of 4-(4-chlorophenyl)-5-methyl-3-{4-[(2-methylphenyl)methoxy]phenyl}-1,2-oxazole

Abstract

In the title compound, C24H20ClNO2, the mean planes of 4-chlorophenyl, 2-methylphenyl and phenylene rings make dihedral angles of 62.8 (2), 65.1 (3) and 15.1 (2)°, respectively, with the 5-methyl-1,2-oxazole ring. In the crystal, molecules are linked by intermolecular C—H...N, C—H...Cl, C—H...π contacts and π–π stacking interactions between the phenylene groups. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (48.7%), H...C/C...H (22.2%), Cl...H/H...Cl (8.8%), H...O/O...H (8.2%) and H...N/N...H (5.1%) interactions.

Vicinal Diaryl-Substituted Isoxazole and Pyrazole Derivatives with In Vitro Growth Inhibitory and In Vivo Antitumor Activity

“…Benzyl analogues differently substituted at 3-(19-23) or 4position (24−29) were not chased further as they demonstrated a significant loss of inhibitory activity (IC 50 values of 12 to >20 μM) for both cell lines except for 20 with 3-methoxy, which showed comparable activity to 11 for the Huh7 cell line (IC 50 = 1.3 vs 3.6 μM). Compounds with dimethyl substitution pattern, i.e., 2,3-diMe (30) or 2,4-diMe (31), suggested that additional methyl group other than 2-methyl was not well tolerated on the benzyl moiety.…”

“…According to the SAR results, compound 11 with 3,4diarylisoxazole and compound 85 with 1,5-diarylpyrazole frameworks were selected for further analysis, and unambiguous structural elucidation of 11 and 85 using the single-crystal X-ray diffraction method was accomplished showing the accurate rearrangement of aromatic rings and atoms in 3Dshape (Figure S1). 29,30 Next, judged by the cellular activity of 11 and 85, both compounds in addition to Huh7, Mahlavu, and MCF7 cell lines were further screened against a panel of the hepatocellular carcinoma (HepG2, SNU475, Hep3B, FOCUS, Hep40, and PLC-PRF-5) and breast cancer (MDA-MB-231, MDA-MB-468, SKBR3, and ZR-75) cell lines along with the nontumorigenic immortalized breast epithelial cells MCF10A (Table 5). The results demonstrated that both compounds are endowed with potent antiproliferative activity against all cancer cells with IC 50 values in the range of 1.3−9.5 μM for 11 and 0.77−7.8 μM for 85 for hepatocellular carcinoma and breast cancer cell lines, while found less toxic to the MCF10A immortalized normal breast epithelial cells (Table 5).…”

Some characteristics of new and innovative COX inhibitor derivatives: Potent hCA‐I and hCA‐II inhibitors supported by molecular docking studies

“…For the synthesis of compound ( 9 ); the cycloaddition reaction of arylnitriloxide ( 8 ) and 4‐chlorophenylacetone ( 7 ) was carried out as in literatures. [ 38,47,48 ]…”

“…For the synthesis of compound (9); the cycloaddition reaction of arylnitriloxide (8) and 4-chlorophenylacetone (7) was carried out as in literatures. [38,47,48] 2.3.1 | Synthesis of 4-(4-[4-chlorophenyl]-5-methylisoxazol-3-yl)phenol (10) The synthesis of compound 10 was prepared as in the literature with little modification. [49] To a solution of compound 9 (1.0 g, 2.66 mmol) and Pd/C (10%, 0.18 g) in ethyl acetate (100 ml) was stirred at room temperature under H 2 atmosphere.…”

“…The synthesis was initiated by 1,3-dipolar cycloaddition. It is think that the aryl nitrile oxides 8 are considered to be a good precursor for 1,3-dipolar cycloaddition to achieved the synthesis of oxygenase inhibitor derivative 9 by using cycloaddition reaction of arylnitrile oxides 8 to the phenylacetone enolate ion 7 regioselectively in the presence of lithium diisopropylamide at 0 C afforded 9 (yield 65%) [38,47,48] debenzylation reaction of compound 9 with Pd/C (10%) in ethyl acetate at room temperature under H 2 atmosphere was afforded compound 10 (Scheme 1). [69] The cyclooxygenase derivative 10 was turned to ftalonitrile compound 11 in DMF using 4-nitrophthalonitrile.…”