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Combination of 4-anilinoquinazoline, arylurea and tertiary amine moiety to discover novel anticancer agents.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2016 Jan 15; Vol. 24 (2), pp. 179-90. Date of Electronic Publication: 2015 Dec 02. - Publication Year :
- 2016
-
Abstract
- In present study, 4-anilinoquinazolines scaffold, arylurea and tertiary amine moiety were combined to design, synthesize gefitinib analogs and discover novel anticancer agents. A series of 4-anilinoquinazoline derivatives (1, 2, 3 and 4) bearing arylurea and tertiary amine moiety at its 6-position were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against A431 cell and A549 cell. The SAR of the title compounds was discussed. The compounds 2d, 2i and 2j with potent antiproliferative activities were evaluated their inhibitory activity against EGFR-TK. Compound 2j displayed potent inhibitory activity against EGFR-TK. In addition, compound 2j, at 50 mg/kg, can completely inhibit cancer growth in established nude mouse A549 xenograft model in vivo. These results suggest that the 4-anilinoquinazoline derivatives bearing diarylurea and tertiary amino moiety at its 6-position can serve as anticancer agents and EGFR inhibitors.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amines chemistry
Aniline Compounds chemistry
Animals
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
ErbB Receptors antagonists & inhibitors
ErbB Receptors metabolism
Humans
Mice
Mice, Nude
Molecular Structure
Neoplasms, Experimental drug therapy
Neoplasms, Experimental pathology
Protein Kinase Inhibitors chemical synthesis
Protein Kinase Inhibitors chemistry
Quinazolines chemistry
Structure-Activity Relationship
Urea analogs & derivatives
Urea chemistry
Amines pharmacology
Aniline Compounds pharmacology
Antineoplastic Agents pharmacology
Protein Kinase Inhibitors pharmacology
Quinazolines pharmacology
Urea pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 26706113
- Full Text :
- https://doi.org/10.1016/j.bmc.2015.12.001