Abstract
A novel series of arylurea and arylamide derivatives 1a–z, 2a–d having aminoquinazoline scaffold was designed and synthesized. Their in vitro antiproliferative activities against RT112 bladder cancer cell line and inhibitory activities against FGFR3 kinase were tested. Most compounds showed good antiproliferative activities against RT112 bladder cancer cell line, and arylurea compounds 1a–z were more potent than arylamide compounds 2a–d. Among them, eight compounds 1a, 1d–g, 1l, 1y, and 1z showed potent activities with GI50values below submicromolar range. Especially, arylurea compounds 1d and 1g possessing 2,3-dimethyl and 3,4-dimethyl moieties exhibited superior or similar antiproliferative activity (GI50 = 8.8 nM and 30.2 nM, respectively) to AZD4547 (GI50 = 29.2 nM) as a reference standard.
Original language | English |
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Pages (from-to) | 5082-5086 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 26 |
Issue number | 20 |
DOIs | |
Publication status | Published - 2016 |
Bibliographical note
Funding Information:This work was funded by the KIST Institutional Program (Grant No. 2E26090 ) from Korea Institute of Science and Technology, and by the Creative Fusion Research Program through the Creative Allied Project funded by the National Research Council of Science & Technology ( CAP-12-1-KIST ).
Publisher Copyright:
© 2016 Elsevier Ltd
Keywords
- Antiproliferative activity
- Arylaminoquinazolinylamides
- Arylaminoquinazolinylureas
- Bladder cancer cell line
- Enzymatic activity
- FGFR3
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry