SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME NEW N6-SUBSTITUTED PURINE NUCLEOSIDES

The synthesis of N6-2-phenoxyethyl-, N6-benzyl, N6-n-pentyl-, N6-n-pentyl-, N6-n-penzyl-, N6-2-pentyl- and N6-2-ethoxyetindadenosines was carried out by quatemization of the N1 of adenosine with ihe appropriatehalide, followed by rearrangement in the product in aqueous NIB, or by nucleophilic subst it ut ion of 6-chloropitrine riboside with the appropriate amino. Also svnthesized were the N6-(Δ2 isopeinenyl) and N6-ally derivatives of the antibiotic tubereidin (7-deazaadenosine). The compounds were examined for biological activity in a number of test, systems, All of the adenosine derivatives examined showed cytokinin activity in the tobacco pith bioassay. Similarly, at low concentrations (10-8 to 10-6M), the N6-substituted adenosines tested stimulated the growth of a human leukemic cell line (6410). At higher concentrations, they decreased the viability of this line of leukemic myeloblasts of line HRIK of Burkin’s lymphoma, and line LKID of leukemic lymphoblasts, whereas they were all ineffeetive against a culture of normal leukocytes. The N-6-substituted tiled tubereidins on the other hand inhibited the normal leukocytes, but were variably effective against the tumor lines. Most of the compounds interfered with the growth of Escherich and some with the growth of Sarcoma 180 cells in vitro. A moderate but significant increase in survival lime of mice beating leukemia 1.1210 was produced by four of the adenosine derivatives. © 1969, American Chemical Society. All rights reserved.