Synthesis and Structural Characterization of Novel Quinazoline–Thiadiazole Aryl-Urea Derivatives with Ortho-Substituted Aryl Groups
محورهای موضوعی : Organic and Inorganic synthesis
Sara Masoudinia
1
,
Marjaneh Samadizadeh
2
,
Alireza Foroumadi
3
,
Hamidreza Bijanzadeh
4
,
Maliheh Safavi
5
1 - Department of Chemistry, CT.C., Islamic Azad University, Tehran, Iran
2 - Department of Chemistry, CT.C., Islamic Azad University, Tehran, Iran
3 - Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4 - Department of Environment, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Tehran, Iran
5 - Biotechnology Dept, Iranian Research Organization for Science and Technology (IROST)
کلید واژه: quinazoline, thiadiazole, aryl urea, synthesis, structural characterization, Anticancer-oriented design,
چکیده مقاله :
Quinazoline and 1,3,4-thiadiazole scaffolds represent privileged heterocycles with broad pharmacological relevance, particularly in the design of anticancer drug candidates. In this study, a novel series of four quinazoline–thiadiazole aryl-urea derivatives (9a–d) was synthesized via a concise two-step protocol. The synthetic route comprised (i) initial coupling of 5-amino-1, 3, 4-thiadiazole-2-thiol with aryl isocyanates to afford N-aryl urea intermediates (8a–d), followed by (ii) nucleophilic aromatic substitution (SNAr) of the thiadiazole moiety with 4-chloro-6-nitroquinazoline to yield the final products (9a–d). The target compounds were obtained in moderate to good yields (62–78%) as crystalline solids. Structural elucidation was accomplished using IR, ¹H and ¹³C NMR spectroscopy, ESI-MS, melting point determination, and elemental analysis, which collectively confirmed the proposed structures. The design strategy was informed by previous work on structurally related quinazoline–thiadiazole ureas with MTT-validated antiproliferative activity, highlighting these new derivatives as promising candidates for further biological evaluation.
Quinazoline and 1,3,4-thiadiazole scaffolds represent privileged heterocycles with broad pharmacological relevance, particularly in the design of anticancer drug candidates. In this study, a novel series of four quinazoline–thiadiazole aryl-urea derivatives (9a–d) was synthesized via a concise two-step protocol. The synthetic route comprised (i) initial coupling of 5-amino-1, 3, 4-thiadiazole-2-thiol with aryl isocyanates to afford N-aryl urea intermediates (8a–d), followed by (ii) nucleophilic aromatic substitution (SNAr) of the thiadiazole moiety with 4-chloro-6-nitroquinazoline to yield the final products (9a–d). The target compounds were obtained in moderate to good yields (62–78%) as crystalline solids. Structural elucidation was accomplished using IR, ¹H and ¹³C NMR spectroscopy, ESI-MS, melting point determination, and elemental analysis, which collectively confirmed the proposed structures. The design strategy was informed by previous work on structurally related quinazoline–thiadiazole ureas with MTT-validated antiproliferative activity, highlighting these new derivatives as promising candidates for further biological evaluation.
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