- Heterocyclic Diamidine DNA Ligands as HOXA9 Transcription Factor Inhibitors: Design, Molecular Evaluation, and Cellular Consequences in a HOXA9-Dependant Leukemia Cell Model
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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
- 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
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p. 1306 - 1329
(2019/02/14)
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- SUSTITUTED ( HETEROARYLMETHYL ) THIOHYDANTOINS AS ANTICANCER DRUGS
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The invention relates to substituted (heteroarylmethyl) thiohydantoin compounds of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, and their use for the preparation of medicaments for the treatment and/or prophylaxis of disorders, in particular of prostate cancer.
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Page/Page column 74-75
(2011/04/18)
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- Synthesis and Antiprotozoal Activity of Aza-Analogues of Furamidine
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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.
- Ismail, Mohamed A.,Brun, Reto,Easterbrook, Judy D.,Tanious, Farial A.,Wilson, W. David,Boykin, David W.
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p. 4761 - 4769
(2007/10/03)
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