619334-28-0Relevant articles and documents
Heterocyclic Diamidine DNA Ligands as HOXA9 Transcription Factor Inhibitors: Design, Molecular Evaluation, and Cellular Consequences in a HOXA9-Dependant Leukemia Cell Model
Depauw, Sabine,Lambert, Mélanie,Jambon, Samy,Paul, Ananya,Peixoto, Paul,Nhili, Raja,Marongiu, Laura,Figeac, Martin,Dassi, Christelle,Paul-Constant, Charles,Billoré, Benjamin,Kumar, Arvind,Farahat, Abdelbasset A.,Ismail, Mohamed A.,Mineva, Ekaterina,Sweat, Daniel P.,Stephens, Chad E.,Boykin, David W.,Wilson, W. David,David-Cordonnier, Marie-Hélène
, p. 1306 - 1329 (2019/02/14)
Most transcription factors were for a long time considered as undruggable targets because of the absence of binding pockets for direct targeting. HOXA9, implicated in acute myeloid leukemia, is one of them. To date, only indirect targeting of HOXA9 expres
Synthesis and Antiprotozoal Activity of Aza-Analogues of Furamidine
Ismail, Mohamed A.,Brun, Reto,Easterbrook, Judy D.,Tanious, Farial A.,Wilson, W. David,Boykin, David W.
, p. 4761 - 4769 (2007/10/03)
6-[5-(4-Amidinophenyl)furan-2-yl]nicotinamidine (8a) was synthesized from 6-[5-(4-cyanophenyl)furan-2-yl]nicotinonitrile (4a), through the bis-O-acetoxyamidoxime followed by hydrogenation. Compound 4a was prepared via selective bromination of 6-(furan-2-yl)nicotinonitrile (2a) with N-bromosuccinimide, followed by Suzuki coupling with 4-cyanophenylboronic acid. In a similar way, diamidines 8b and 8c were prepared from the dicyano derivatives 4c and 4d, respectively. N-Methoxy-6-[5-[4-(N-methoxyamidino)phenyl]-furan-2-yl}-nicotinamidine (6a) was prepared via methylation of the respective diamidoxime 5a with dimethylsulfate. Prodrugs 6b and 6c were also prepared by methylation of the respective diamidoximes 5b and 5d. The symmetrical diamidines 14a,b were synthesized through the corresponding bis-O-acetoxyamidoxime followed by hydrogenation. The key compounds 11a,b were conveniently obtained by Stille coupling between 2,5-bis(tri-n-butylstannyl)furan and the corresponding heteroaryl halides. These compounds have been evaluated in vitro for activity against Trypanosoma b. rhodesiense (T. b. r.) and P. falciparum (P. f.). The diamidines 8a, 8c, and 14b gave IC50 values versus T. b. r. of less than 10 nM. Against P. f. 8a, 8b, and 14b exhibited IC50 values less than 10 nM. In an in vivo mouse model for T. b. r. four compounds 6a, 6c, 6d, and 8a were curative. Compound 6a produced cures at an oral dosage of 5 mg/kg.
