PROCESS FOR PREPARING IMMUCILLINS HAVING A METHYLENE LINK
The invention relates to a process for preparing compounds that are inhibitors of nucleoside phosphorylases and nucleosidases, in particular, compounds that have a methylene link between a nucleoside base analogue moiety of the molecule and a sugar analogue moiety, via an amino nitrogen of the sugar analogue moiety.
-
Page/Page column 41
(2009/07/25)
A facile synthesis of 9-deaza analogue of olomoucine
Heating of 6-(benzylamino)-2-chloro-9-deazapurine (3) with ethanolamine afforded 6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-deazapurine (8). Its treatment with formaldehyde in alkaline solution, after protection of the OH group with DMTr, led to hydroxymethylation at position 9. Conversion of the hydroxymethyl group to methyl was performed by catalytic hydrogenation under simultaneous deprotection, which resulted in the formation of the 9-deaza analogue 1 of olomoucine. Compound 1 does not exhibit any significant in vitro cell growth inhibition of CCRF-CEM, HeLa and L-1210 cell lines. Cytostatic activity was found in 6-(benzylamino)-9-deazapurine (2) and its 2-chloro derivative 3 in CCRF-CEM cells with IC50 13.3 and 15:8 μM, respectively.