Hetaryl derivatives of 7-deazapurine ribonucleosides: potent cytostatic agents

0361524 - ÚOCHB 2012 CZ eng C - Konferenční příspěvek (zahraniční konf.)
Perlíková, Pavla - Nauš, Petr - Bourderioux, Aurelie - Hocek, Michal
Hetaryl derivatives of 7-deazapurine ribonucleosides: potent cytostatic agents.
Chemistry of Nucleic Acid Components. 15th Symposium. Praha: Institute of Organic Chemistry and Biochemistry AS CR, v. v. i., 2011 - (Hocek, M.), s. 194-197. Collection Symposium Series, 12. ISBN 978-80-86241-37-1.
[Chemistry of Nucleic Acid Components /15./. Český Krumlov (CZ), 05.06.2011-10.06.2011]
Grant CEP: GA MŠMT 1M0508; GA AV ČR 1QS400550501; GA ČR GAP207/11/0344
Výzkumný záměr: CEZ:AV0Z40550506
Klíčová slova: nucleosides * 7-deazapurines * cytostatic
Kód oboru RIV: CC - Organická chemie

A series of novel 7-deazapurine ribonucleosides substituted with aryl and hetaryl groups has been prepared. Suzuki or Stille cross-coupling reactions with 6-chloro-7-deazapurine ribonucleosides substituted with H, F of Cl atom in position 7 were used in the key step of the synthesis. Either cross-coupling of protected ribonucleoside with appropriate (het)arylboronic acid or stannane followed by deprotection, or single-step aqueous-phase Suzuki cross-coupling reaction of unprotected 7-deazapurine ribonucleoside with boronic acid provided target (het)aryl-7-deazapurine ribonucleosides. 6-Furyl- and 6-thienyl-7-deazapurine ribonucleosides showed cytostatic effect in multiple cancer cell lines in nanomolar range. Application of cyclosaligenyl and alanyl-ester phosphoramidate prodrugs did not improved cytostatic activity of parent nucleosides.
Trvalý link: http://hdl.handle.net/11104/0198822