16344-26-6Relevant articles and documents
Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia
Sykes, David B.,Kfoury, Youmna S.,Mercier, Fran?ois E.,Wawer, Mathias J.,Law, Jason M.,Haynes, Mark K.,Lewis, Timothy A.,Schajnovitz, Amir,Jain, Esha,Lee, Dongjun,Meyer, Hanna,Pierce, Kerry A.,Tolliday, Nicola J.,Waller, Anna,Ferrara, Steven J.,Eheim, Ashley L.,Stoeckigt, Detlef,Maxcy, Katrina L.,Cobert, Julien M.,Bachand, Jacqueline,Szekely, Brian A.,Mukherjee, Siddhartha,Sklar, Larry A.,Kotz, Joanne D.,Clish, Clary B.,Sadreyev, Ruslan I.,Clemons, Paul A.,Janzer, Andreas,Schreiber, Stuart L.,Scadden, David T.
, p. 171 - 15,186 (2016)
While acute myeloid leukemia (AML) comprises many disparate genetic subtypes, one shared hallmark is the arrest of leukemic myeloblasts at an immature and self-renewing stage of development. Therapies that overcome differentiation arrest represent a power
Synthesis and antiproliferative activity of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety
Tang, Qidong,Duan, Yongli,Wang, Linxiao,Wang, Min,Ouyang, Yiqiang,Wang, Caolin,Mei, Han,Tang, Sheng,Xiong, Yinhua,Zheng, Pengwu,Gong, Ping,Zhu, Wufu
, p. 266 - 275 (2017/12/07)
A series of pyrrolo[2,3-b]pyridine derivatives bearing the 1,8-naphthyridin-2-one moiety were synthesized, and evaluated for their antiproliferative activity against four cancer cell lines (HT-29, A549, H460, and U87MG) and six tyrosine kinases (c-Met, Flt-3, PDGFR-β VEGFR-2, EGFR, and c-Kit) inhibitory activities in vitro. Most compounds showed moderate to excellent potency, with the most promising analogue 32 showing Flt-3/c-Met IC50 value of 1.16/1.92 nM. Structure-activity relationship studies indicated that the hydrogen atom served as R1 group was benefited to the potency, and mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring (such as R3 = 4-F) showed a higher preference for antiproliferative activity.
Synthesis and antiproliferative activity of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety
Tang, Qidong,Duan, Yongli,Xiong, Hehua,Chen, Ting,Xiao, Zhen,Wang, Linxiao,Xiao, Yueyue,Huang, Shunmin,Xiong, Yinhua,Zhu, Wufu,Gong, Ping,Zheng, Pengwu
, p. 201 - 213 (2018/09/18)
A series of 6,7-disubstituted-4-phenoxyquinoline derivatives bearing the 1,8-naphthyridin-2-one moiety were designed, synthesized and evaluated for their biological activities. The target compounds exhibited moderate to high antiproliferative activity against three cancer cell lines (A549, HepG2 and MCF-7) and several compounds (25, 27, 33, 37, 41, 43, 49 and 53) were evaluated for the activity against c-Met kinase. The most promising compound 33 (IC50 c-Met = 2.36 nM) showed excellent activity against A549, HepG2 and MCF-7 cell lines with IC50 values of 0.23 μM, 0.42 μM and 0.21 μM, respectively, which was 1.5–2.1 times of the positive control. Furthermore, compound 33 was evaluated for the activity against Flt3, PDGFR-α PDGFR-β c-Kit, Flt4, ALK and EGFR kinase. Structure activity relationship studies indicated that mono-EWGs (such as R2 = F) at 4-position of moiety C was a key factor in improving the antitumor activity. In addition, further research on compound 33 was mainly including concentration dependence, apoptosis (acridine orange staining), apoptosis result analyzing and molecular docking.
