2. Academic Validation
  3. Design and synthesis of quinazolinones as EGFR inhibitors to overcome EGFR resistance obstacle

Design and synthesis of quinazolinones as EGFR inhibitors to overcome EGFR resistance obstacle

  • Bioorg Med Chem. 2017 May 15;25(10):2713-2723. doi: 10.1016/j.bmc.2017.03.039.
Harun M Patel 1,  Rahul Pawara 2,  Azim Ansari 2,  Malleshappa Noolvi 3,  Sanjay Surana 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, District Dhule 425 405, Maharashtra, India. Electronic address: hpatel_38@yahoo.com.
  • 2 Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, District Dhule 425 405, Maharashtra, India.
  • 3 Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim (Surat) 3941110, Gujarat, India.
PMID: 28366268 DOI: 10.1016/j.bmc.2017.03.039
Abstract

The epidermal growth factor receptor (EGFR) T790M mutant is found in about 50% of clinically acquired resistance to gefitinib among patients with non-small cell lung Cancer (NSCLC). New derivatives of 4(3H)-quinazolinones were synthesized and evaluated for their inhibitory activity against NSCLC. The results of the study demonstrated that compound 79, 7-chloro-3-(5-(4-methoxyphenyl)-1,3,4-thiadiazol-2-yl)-2-phenylquinazolin-4(3H)-one was found to be the most potent compounds of the series with IC50 value of 0.031μM against mutant T790M/L858R EGFR. Compounds 15, 51, 73, 75, 78, 79 and 96 were less potent against A549 (WT EGFR and K-Ras mutation) and HT-29 (non-special gene type) cells, showing a high safety index. The obtained results showed that compounds 15, 51, 73, 75, 78, 79 and 96 could be the promising template to overcome drug resistance mediated by the EGFR T790 Mutant.

Keywords

Non Small Cell Lung Cancer; Quinazoline; T790M EGFR.

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