Knies, Christine published the artcileSynthesis of new potential lipophilic co-drugs of 2-Chloro-2′-deoxyadenosine (Cladribine, 2-CdA, Mavenclad, Leustatin) and 6-Azauridine (z6U) with valproic acid, Application In Synthesis of 539-88-8, the main research area is cladribine azauridine valproate synthesis lipophilic anticancer; biological activity; cancerostatic/cancerotoxic activity; cladribine; drug profiling; glioblastoma; multiple sclerosis; nucleolipids.
2-Chloro-2′-deoxyadenosine (cladribine, 1) was acylated with valproic acid (2) under various reaction conditions yielding 2-chloro-2′-deoxy-3′,5′-O-divalproyladenosine (3) as well as the 3′-O- and 5′-O-monovalproylated derivatives, 2-chloro-2′-deoxy-3′-O-valproyladenosine (4) and 2-chloro-2′-deoxy-5′-O-valproyladenosine (5), as new co-drugs. In addition, 6-azauridine-2′,3′-O-(Et levulinate) (8) was valproylated at the 5′-OH group (â?). All products were characterized by 1H- and 13C-NMR spectroscopy and ESI mass spectrometry. The structure of the byproduct 6 (N-cyclohexyl-N-(cyclohexylcarbamoyl)-2-propylpentanamide), formed upon valproylation of cladribine in the presence of N,N-dimethylaminopyridine and dicyclohexylcarbodiimide, was analyzed by X-ray crystallog. Cladribine as well as its valproylated co-drugs were tested upon their cancerostatic/cancerotoxic activity in human astrocytoma/oligodendroglioma GOS-3 cells, in rat malignant neuro ectodermal BT4Ca cells, as well as in phorbol-12-myristate 13-acetate (PMA)-differentiated human THP-1 macrophages. The most important result of these experiments is the finding that only the 3′-O-valproylated derivative 4 exhibits a significant antitumor activity while the 5′-O- as well as the 3′,5′-O-divalproylated cladribine derivatives 3 and 5 proved to be inactive.
Chemistry & Biodiversity published new progress about Antitumor agents. 539-88-8 belongs to class esters-buliding-blocks, name is Ethyl 4-oxopentanoate, and the molecular formula is C7H12O3, Application In Synthesis of 539-88-8.
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Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics