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

• Published in: Journal of medicinal chemistry Vol. 33; no. 4; pp. 1220 - 1225
• Main Authors: Ramasamy, Kandasamy, Imamura, Nobutaka, Hanna, Naeem B, Finch, Rick A, Avery, Thomas L, Robins, Roland K, Revankar, Ganapathi R
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-04-1990
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Carbohydrates. Nucleosides and nucleotides; Chemical Phenomena; Chemistry; Exact sciences and technology; Female; Leukemia L1210 - drug therapy; Mice; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Preparations and properties; Purine Nucleosides - chemical synthesis; Purine Nucleosides - therapeutic use; Pyrimidine Nucleosides - chemical synthesis; Pyrimidine Nucleosides - pharmacology; Ribonucleosides - therapeutic use; Structure-Activity Relationship; Sulfides - therapeutic use; Sulfonamides - therapeutic use; Sulfoxides - therapeutic use; Antineoplastic agent; Sulfonamide; Nitrogen heterocycle; Rodentia; Sulfinamide; Guanidines; L1210-Leukemia; Biological activity; Vertebrata; Mammalia; Mouse; Analog; Animal; Bicyclic compound; Sulfenamide; Nucleoside; Ribonucleoside
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00166a021

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%.