ABSTRACT
Objective Using Ex-Rad as a lead compound to design and synthesize aroyl derivatives with protein tyrosine kinases(PTK) inhibitiory activity. Methods 1-[(4-Fluorophenyl)amioncarbonyl] cyclopropanecarboxylic acid, and 2-oxo-1-phenylimidazolidine were used as raw materials to synthesize intermediates 3a-3d, respectively. The target compounds T1-T7 were synthesized by chloroformylation reaction with 3a-3d. Enzyme-linked immunosorbent assay (ELISA) was used and inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Results Seven new compounds containing aroyl groups were synthesized and their structures were confirmed by 1H NMR. The evaluation of the seven compounds demonstrated that PTK inhibitory activity of T2 and T6 were stronger than that of the lead compound. Conclusion The synthetic method is simple, and the materials are cheap and readily available. T2 and T6 show strong PTK inhibitory activity by ELISA.
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Objective To explore the relationship between mutation status of epidermal growth factor receptor (EGFR) and efficacy of EGFR tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced nonsmall ccll lung cancer (NSCLC).Methods The data of 72 outpatients and inpatients with stage Ⅲ b/ⅣNSCLC diagnosed by histopathology and harbored EGFR-activating mutations (exon 19 and exon 21) from January 2008 to December 2013 in Xuzhou Cancer Hospital were collected.All of them received first-line EGFR-TKI.The relationships between EGFR gene status and response rate or progression-free survival (PFS)were analyzed.Results Of the 72 patients with EGFR mutation,37 patients harbored exon 19 deletion,and 35 patients harbored exon 21 L858R point mutation.The efficacies of all patients were assessable.The objective response rate (ORR) was 63.9 ％ (46/72) and disease control rate (DCR) was 79.2 ％ (57/72) in all patients,including 2 cases of complete remission (CR),44 cases of partial remission (PR),1 1 cases stable disease (SD) and 15 cases of disease progression (PD).Patients with exon 19 deletion had a higher ORR [75.7 ％ (28/37) vs 51.4 ％ (18/35),P =0.032] and a higher DCR [89.2 ％ (33/37) vs 68.6 ％ (24/35),P =0.031]than patients with exon 21 L858R mutation.The PFS of patients with exon 19 deletion was significantly longer than that of patients with exon 21 L858R mutation (12.0 months vs 9.5 months,P =0.030).Cox multivariate analysis indicated that the gender,histological type,smoking history were the major influence factors of PFS.The differences of toxicity between the two groups were not significant.Conclusion EGFR-activating mutation is a predictor for PFS and ORR of first-line EGFR-TKI in patients with advanced NSCLC.
ABSTRACT
Objective Using Ex-Rad as a lead compound to design and synthesize aroyl derivatives with protein tyrosine ki?nases(PTK)inhibitiory activity. Methods 1-[(4-Fluorophenyl)amioncarbonyl]cyclopropanecarboxylic acid,and 2-oxo-1-phenyl-imidazolidine were used as raw materials to synthesize intermediates 3a-3d,respectively. The target compounds T1-T7 were synthe?sized by chloroformylation reaction with 3a-3d. Enzyme-linked immunosorbent assay(ELISA)was used and inhibitory rate was calcu?lated to screen out the compounds with PTK inhibitory activity. Results Seven new compounds containing aroyl groups were synthe?sized and their structures were confirmed by 1H NMR. The evaluation of the seven compounds demonstrated that PTK inhibitory activi?ty of T2 and T6 were stronger than that of the lead compound. Conclusion The synthetic method is simple,and the materials are cheap and readily available. T2 and T6 show strong PTK inhibitory activity by ELISA.
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Objective To use Ex-Rad as a lead compound to design and synthesize aryl benzyl sulfones derivatives with protein tyrosine kinase’(PTK) inhibitory activity. Methods 2-Naphthol was used as a raw material to synthesize intermediates 3a-3f. The target compounds 4a, 4d, and 5a-5f were synthesized by oxidizing 3a-3f in acetic acid with H202. Enzyme-linked immunosorbent assay’ELISA) was used and inhibition rate was calculated to screen out the compounds with PTK inhibitory activitity. Results Eight compounds containing a sulfone or sulfoxide group were synthesized and the structures were confirmed by 1H NMR. Preliminary evaluation of the 8 compounds demonstrated that the PTK inhibitory activity of 5c was much stronger than that of the lead compound. Conclusion The synthetic method is simple, and the materials are cheap and readily available. 5c shows strong PTK inhibitory activity by ELISA.
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Objective To use Ex-Rad as a lead compound to design and synthesize aryl benzyl sulfones derivatives with protein tyrosine kinases(PTK) inhibitory activity. Methods 2-Naphthol was used as a raw material to synthesize intermediates 3a-3f. The target compounds 4a, 4d, and 5a-5f were synthesized by oxidizing 3a-3f in acetic acid with H2O2. Enzyme-linked immunosorbent assay(ELISA) was used and inhibition rate was calculated to screen out the compounds with PTK inhibitory activitity. Results Eight compounds containing a sulfone or sulfoxide group were synthesized and the structures were confirmed by 1H NMR. Preliminary evaluation of the 8 compounds demonstrated that the PTK inhibitory activity of 5c was much stronger than that of the lead compound. Conclusion The synthetic method is simple, and the materials are cheap and readily available. 5c shows strong PTK inhibitory activity by ELISA.
ABSTRACT
No abstract available.