Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma. Issue 4 (15th February 2018)

• Record Type: Journal Article
• Authors: Czudor, Zsófia; Balogh, Mária; Bánhegyi, Péter; Boros, Sándor; Breza, Nóra; Dobos, Judit; Fábián, Márk; Horváth, Zoltán; Illyés, Eszter; Markó, Péter; Sipos, Anna; Szántai-Kis, Csaba; Szokol, Bálint; Őrfi, László
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 4(2018)
• Page Start: 769
• Page End: 773
• Publication Date: 2018-02-15
• Subjects: Cyclin dependent kinase inhibitor -- 2, 4-Disubstituted pyrimidine -- Multiple myeloma -- Polo-like kinase; DGGRGPAHRNGGGK-UHFFFAOYSA-N -- IZZPOWGOQQEMLG-UHFFFAOYSA-N -- XXDWIVIRVZIFRJ-UHFFFAOYSA-N -- LJDYPDFYDYUVQU-UHFFFAOYSA-N -- UCWVJKDAOWZSON-UHFFFAOYSA-N -- POGNPTQDNAQQHP-UHFFFAOYSA-N -- SQDBBCVTQUGHRC-UHFFFAOYSA-N -- KVUJFXCKUWCAPJ-UHFFFAOYSA-N -- OKTBQOSRYWOIII-UHFFFAOYSA-N -- UELOOJSFABABRA-UHFFFAOYSA-N -- OWNZUOGSQJYNKZ-UHFFFAOYSA-N -- ZCDUOQKIBPNQKR-UHFFFAOYSA-N -- DLIHXKHNLRECAW-UHFFFAOYSA-N -- MTCHECYESPQBRP-UHFFFAOYSA-N -- QYPIOFVEFYRHEE-UHFFFAOYSA-N -- VBKVWKOFOQLPFP-UHFFFAOYSA-N -- DGUIZLRMDHYSDD-UHFFFAOYSA-N -- NYQNUBTYFILRQK-UHFFFAOYSA-N -- XQMJJSXWIZNCQL-UHFFFAOYSA-N -- LQZTVNWHEICJJE-UHFFFAOYSA-N -- BZMRXLJOOHPIIU-UHFFFAOYSA-N -- CUCBJZSGNZBKEE-UHFFFAOYSA-N -- AJXDBLPSUPQKBJ-UHFFFAOYSA-N -- ZBJGREHWROGYRW-UHFFFAOYSA-N -- CIKHZDKMTDPCLM-UHFFFAOYSA-N -- ZVLFDFWFDUVCGU-UHFFFAOYSA-N -- FPPDWTSDSZADQO-UHFFFAOYSA-N -- MECDFEWXMIUNSU-UHFFFAOYSA-N -- WCQPPPLDPGLXOK-UHFFFAOYSA-N -- CUCSXQCVIUDKLI-UHFFFAOYSA-N -- MFGPPACYEFGSTK-UHFFFAOYSA-N -- BFSKFHZFACZLER-UHFFFAOYSA-N -- FKCFTFILSPYLMY-UHFFFAOYSA-N -- JELDXXKXSFSHOQ-UHFFFAOYSA-N -- HTWRNSUAXNIUCQ-UHFFFAOYSA-N -- CGJSARMCXCGGCW-UHFFFAOYSA-N -- XYWHOWNTZXFAKW-UHFFFAOYSA-N -- SWSRKLYGLXMTAH-UHFFFAOYSA-N -- ZFEUWTMEXIDLMB-UHFFFAOYSA-N -- MPAQAURRGMTTKV-UHFFFAOYSA-N -- LVQNVBAEMYBEOA-UHFFFAOYSA-N -- XRANJRXEZLWYJP-UHFFFAOYSA-N -- PEFQLFPPRNGLJD-UHFFFAOYSA-N -- ZZIVLVSLTIYADD-UHFFFAOYSA-N -- LNRMRFAGLGEVBC-UHFFFAOYSA-N -- ORCMTKOVGLGATH-UHFFFAOYSA-N -- BQRWVMGYVBRTGW-UHFFFAOYSA-N -- OFFZTZQPFQQGKB-UHFFFAOYSA-N -- VGAJDLUOYXTTRJ-UHFFFAOYSA-N -- OBMIDCIHJHNZFZ-UHFFFAOYSA-N -- DNGLPAVFEOLFIO-UHFFFAOYSA-N -- OWQKUKUKXLQRLY-UHFFFAOYSA-N -- LRXZVWVFJCSXSV-UHFFFAOYSA-N -- WBEAFTGSPZEEIR-UHFFFAOYSA-N -- XWXGKRQCUJICNZ-UHFFFAOYSA-N -- WKDOKJKUKSSFSB-UHFFFAOYSA-N -- ZMZIPHROZUBATK-UHFFFAOYSA-N -- MLTGOCWSTUBXGD-UHFFFAOYSA-N -- AGVKMSHAHBUJMI-UHFFFAOYSA-N -- WNQPHLAUPBBBFU-UHFFFAOYSA-N -- HHCOUYYRWHXUAC-UHFFFAOYSA-N -- NTMUINUAJVCMDH-UHFFFAOYSA-N -- QEVPCFCNOLNUJL-UHFFFAOYSA-N -- CKUHEEMBETZXOQ-UHFFFAOYSA-N -- HWXHRSCEACQBKJ-UHFFFAOYSA-N -- DGVJWXLMYXXGHA-UHFFFAOYSA-N -- ZNYWIWXWOHYBON-UHFFFAOYSA-N -- HQVUAGCBAZOMFE-UHFFFAOYSA-N -- MDOPSPOMDXUNGM-UHFFFAOYSA-N -- DITJTRMRKAMYBI-UHFFFAOYSA-N -- REBRCFSKMUTQDS-UHFFFAOYSA-N; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.01.002
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2, 4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).