1. DESIGN, SYNTHESIS, CRYSTAL STRUCTURE AND BIOLOGICAL EVALUATION OF NOVEL 4-ARYLAMINOQUINAZOLINE DERIVATIVES AS POTENT CYTOTOXIC AGENTS.
- Author
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Xiao Han, Liang Liang Chi, Wei Tao Qin, Ling Hou, Zhi Qiang Cai, Wen Jie Ren, and Le Kun Wei
- Subjects
CRYSTAL structure ,MORPHOLOGY ,MONOCLINIC crystal system ,SINGLE crystals ,X-ray diffraction - Abstract
A series of novel 4-arylaminoquinazoline derivatives were synthesized by five-step reactions, the structure was characterized by IR, 1H NMR, MS and single crystal X-ray diffraction. The result of 5aX crystal was as follows: the crystal belongs to the monoclinic system, space group P21/c with a = 12.3637(4) Å, b = 12.7902(2) Å, c = 13.2240(5) Å, α = 90°, β = 117.030(5)°, γ = 90°, V = 1862.75(12) Å3, Z = 2, F(000) = 804.0, µ = 0.095 mm-1, S = 1.039, R = 0.0569, wR = 0.1535 for 8417 observed reflections with I > 2σ(I). The compound 5cX exhibited an excellent inhibitory effect on the cell line A549 (IC
50 < 2.5 µM) and the drug-resistant cell line H1975 (IC50 < 2.5 µM) by the biological activity, which were superior to the positive control Zorifertinib (against A549: IC50 = 31.08 µM; against H1975: IC50 = 64.17 µM). Molecular docking revealed that the better inhibitory activity of compound 5cX was owing to the combining EGFRWT and EGFRL858R/T790M by hydrogen bonding. The physicochemical properties of the compounds were predicted by using ADME data analysis, and the results showed that the compounds all obeyed Lipinski's five rules. [ABSTRACT FROM AUTHOR]- Published
- 2023
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