TY - JOUR
T1 - Synthesis of novel arylaminoquinazolinylurea derivatives and their antiproliferative activities against bladder cancer cell line
AU - Kim, Jung Hun
AU - Kwak, Yeonui
AU - Song, Chiman
AU - Roh, Eun Joo
AU - Oh, Chang Hyun
AU - Lee, So Ha
AU - Sim, Taebo
AU - Choi, Jung Hoon
AU - Yoo, Kyung Ho
N1 - 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
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Antiproliferative activity
KW - Arylaminoquinazolinylamides
KW - Arylaminoquinazolinylureas
KW - Bladder cancer cell line
KW - Enzymatic activity
KW - FGFR3
UR - http://www.scopus.com/inward/record.url?scp=84988911818&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2016.08.076
DO - 10.1016/j.bmcl.2016.08.076
M3 - Article
C2 - 27599742
AN - SCOPUS:84988911818
VL - 26
SP - 5082
EP - 5086
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 20
ER -