Synthesis of novel arylaminoquinazolinylurea derivatives and their antiproliferative activities against bladder cancer cell line.
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=8.8nM and 30.2nM, respectively) to AZD4547 (GI50=29.2nM) as a reference standard.
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.
Jung Hun
JH
Kim
Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Yeonui
Y
Kwak
Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Chiman
C
Song
Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Eun Joo
EJ
Roh
Center for Biomaterials, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Chang-Hyun
CH
Oh
Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
So Ha
SH
Lee
Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
Taebo
T
Sim
Department of Chemistry, Hanyang University, Seoul 133-791, Republic of Korea.
Jung Hoon
JH
Choi
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.
Kyung Ho
KH
Yoo
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014508:Urea / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D011799:Quinazolines; D014508:Urea
Antiproliferative activity; Arylaminoquinazolinylamides; Arylaminoquinazolinylureas; Bladder cancer cell line; Enzymatic activity; FGFR3