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Figure 1.

Figure 2.

Ethyl 2-[(6,7-dimethoxyquinazolin-4-yl)amino]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate (15b)

Yield: 76%; mp: 254–256°C; IR (cm⁻¹): 3200 (NH), 2974, 2854 (CH-aliphatic), 1656 (C=O); ¹H NMR (DMSO-d₆) δ ppm 1.03 (t, 3H, CH₃CH₂, J = 7.2 Hz), 1.21 (t, 2H, CH₂, J = 6.9 Hz), 2.88 (t, 2H, CH₂, J = 6.9 Hz), 3.40 (q, 2H, CH₂, J = 6.9 Hz), 3.88 (s, 3H, OCH₃), 3.91 (s, 3H, OCH₃), 3.96 (m, 4H, 2 CH₂), 4.24 (q, 2H, CH₃CH₂, J = 7.2 Hz), 7.40 (s, 1H, Ar-H), 7.62 (s, 1H, Ar-H), 8.99 (s, 1H, Ar-H), 12.00 (s, 1H, NH, D₂O exchangeable); Anal. Calcd for C₂₂H₂₅N₃O₄S: C, 61.81; H, 5.89; N, 9.83. Found: C, 61.93; H, 5.96; N, 9.98.

General procedure for the synthesis of compounds 15a,15b

A mixture of 4-chloro-6,7-dimethoxyquinazoline (1) (0.22 g, 1 mmol) and ethyl 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate (14a) or ethyl 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate (14b) (1 mmol) in isopropanol (15 mL) was heated under reflux for 10 h. The reaction was cooled, and the solid formed was filtered, dried, and crystallized from isopropanol.

Synthesis of 4-Heteroaryl–Quinazoline Derivatives as Potential Anti-breast Cancer Agents

A. E. Kassab, E. M. Gedawy, H. B. El-Nassan+

+Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt

E-mail: hala_bakr@hotmail.com

DOI10.1002/jhet.2634,

http://onlinelibrary.wiley.com/doi/10.1002/jhet.2634/full?elq_mid=11879&elq_cid=4828550

Asmaa Elsayed Abd Ellatief Kassab( A. E. Kassab)

4-Heteroaryl or heteroalkyl–quinazoline derivatives were prepared as dual epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors. The new compounds were tested for their dual enzyme inhibition as well as their cytotoxic activity on MCF7 cell line. The results indicated that almost all the compounds showed moderate dual inhibition of both enzymes. Compound 3 (methyl piperidine-4-carboxylate derivative) showed the highest inhibitory activity against both enzymes with IC₅₀ 97.6 and 64.0 µM against EGFR and VEGFR-2 kinases, respectively. Most of the test compounds showed potent to moderate antitumor activity on MCF7 cell line. Five compounds (3, 9c, 11, 13, and 15b) showed potent cytotoxic activity with IC₅₀values between 10 and 17 µM.