2. Academic Validation
  3. Synthesis of novel arylaminoquinazolinylurea derivatives and their antiproliferative activities against bladder cancer cell line

Synthesis of novel arylaminoquinazolinylurea derivatives and their antiproliferative activities against bladder cancer cell line

  • Bioorg Med Chem Lett. 2016 Oct 15;26(20):5082-5086. doi: 10.1016/j.bmcl.2016.08.076.
Jung Hun Kim 1,  Yeonui Kwak 2,  Chiman Song 2,  Eun Joo Roh 2,  Chang-Hyun Oh 3,  So Ha Lee 2,  Taebo Sim 2,  Jung Hoon Choi 4,  Kyung Ho Yoo 5
Affiliations

Affiliations

  • 1 Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Chemistry, Hanyang University, Seoul 133-791, Republic of Korea.
  • 2 Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
  • 3 Center for Biomaterials, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
  • 4 Department of Chemistry, Hanyang University, Seoul 133-791, Republic of Korea.
  • 5 Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea. Electronic address: khyoo@kist.re.kr.
PMID: 27599742 DOI: 10.1016/j.bmcl.2016.08.076
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 GI50 values 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=8.8nM and 30.2nM, respectively) to AZD4547 (GI50=29.2nM) as a reference standard.

Keywords

Antiproliferative activity; Arylaminoquinazolinylamides; Arylaminoquinazolinylureas; Bladder cancer cell line; Enzymatic activity; FGFR3.

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