Synthesis and antitumor evaluation in mice of certain 7-deazapurine (pyrrolo[2,3-d]pyrimidine) and 3-deazapurine (imidazo[4,5-c]pyridine) nucleosides structurally related to sulfenosine, sulfinosine, and sulfonosine

Abstract

7-Deaza (pyrrolo[2,3-d]pyrimidine) and 3-deaza (imidazo[4,5-c]pyridine) congeners of sulfenosine (5a and 9), sulfinosine (6a and 10), and sulfonosine (7a) have been prepared and evaluated for their antileukemic activity in mice. Amination of 2-amino-7-beta-D-ribofuranosylpyrrolo[2,3-d]pyrimidine-4(3H)-th ion e (4a) and its 2'-deoxy analogue (4c) with a chloramine solution gave the corresponding 4-sulfenamides (5a and 5c, respectively), which on selective oxidation with m-chloroperoxybenzoic acid (MCPBA) gave the respective diastereomeric 2-amino-7-beta-D-ribofuranosyl-pyrrolo[2,3-d]pyrimidine-4-sulfinamide (7-deazasulfinosine, 6a) and its 2'-deoxy derivative (6c). A similar amination of 7-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo[2,3-d]pyrimidine-4(3H)- thione (4b) gave the corresponding 4-sulfenamide derivative (5b). Oxidation of 5b with 1 molar equiv of MCPBA furnished (R,S)-7-(2-deoxy-beta-D-erythro-pentofuranosyl)pyrrolo[2,3-d]pyrimidine- 4- sulfinamide (6b), whereas use of excess of MCPBA afforded the corresponding sulfonamide derivative (7b). Treatment of 3-deaza-6-thioguanosine (8) with a chloramine solution gave 3-deazasulfenosine (6-amino-1-beta-D- ribofuranosylimidazo[4,5-c]pyridine-4-sulfenamide, 9). Controlled oxidation of 9 with MCPBA afforded 3-deazasulfinosine (10). As gauged by increases in the mean postinoculation life spans of L1210 inoculated mice, none of these nucleosides exhibited biologically significant activity (T/C greater than or equal to 125). Even so, antileukemic activity appeared to be influenced, albeit not uniformly, by structural modifications in the base and carbohydrate moieties of sulfenosine and sulfinosine. Thus, while several of the compounds were lacking in cytotoxic activity, eight others (4c, 5a, 5c, 6a, 6b, 7b, 9, and 10) were estimated to have reduced body burdens of viable L1210 cells by 16-77%.

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target

“…Route 5 includes thiols or disulfides, sulfinates, sulfamoyl salts, sulfonyl azides, or silyl sulfides that have been oxidized in halogenating and non‐halogenating conditions . Example of route 6 is the direct oxidation of sulfenamides to sulfonamides with permanganate or meta ‐chloroperoxybenzoic acid (MCPBA) …”

An efficient and facile synthesis of N-Cbz-β-aminoalkanesulfonamides

“…Inversely, there is still growing interest in -aminoalkanesulfonamides due to the fact that they can be considered as stable mimetics of tetrahedral transition states in hydrolysis and formation of esters and amides [2]. Therefore, they have been widely used as enzyme inhibitors [3,4], antibacterial [57] and anticancer agents [8]. Additionally, N-protected -aminoalkanesulfonamides as useful building blocks have been successfully employed in the synthesis of sulfonopeptides [1] and hybrid sulfonophosphinopeptides [9,10].…”

Electrochemical study of catechols in the presence of 4,6-dihydroxy-2-methylpyrimidine

“…Pyrimidines are an important class of heteroaromatic compounds and have widespread applications from pharmaceuticals to materials. A number of pyrimidines are known to have antimicrobial and antitumor activities [15][16][17][18], and a number of benzofuran derivatives are known to have biological activities and to be active in anticancer agent research [19,20]. The importance of these compounds has encouraged their use to investigate the electrochemical oxidation of catechols in the presence of 4,6-dihydroxy-2-methylpyrimidine as a nucleophile and the synthesis of some new compounds from benzofuro [2,3-d] pyrimidines.…”