123002-38-0Relevant articles and documents
Synthesis and Antitumor Evaluation in Mice of Certain 7-Deazapurine (Pyrrolopyrimidine) and 3-Deazapurine (Imidazopyridine) Nucleosides Structurally Related to Sulfenosine, Sulfinosine, and Sulfonosine
Ramasamy, Kandasamy,Imamura, Nobutaka,Hanna, Naeem B.,Finch, Rick A.,Avery, Thomas L.,et al.
, p. 1220 - 1225 (1990)
7-Deaza (pyrrolopyrimidine) and 3-deaza (imidazopyridine 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-β-D-ribofuranosylpyrrolopyrimidine-4(3H)-thione (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-β-D-ribofuranosylpyrrolopyrimidine-4-sulfinamide (7-deazasulfinosine, 6a) and its 2'-deoxy derivative (6c).A similar amination of 7-(2-deoxy-β-D-erythro-pentofuranosyl)pyrrolopyrimidine-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-β-D-erythro-pentofuranosyl)pyrrolopyrimidine-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-β-D-ribofuranosylimidazopyridine-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 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 16-77percent.
Synthesis and in vivo antitumor activity of 2-amino-9H-purine-6-sulfenamide, -sulfinamide, and -sulfonamide and related purine ribonucleosides
Revankar,Hanna,Imamura,Lewis,Larson,Finch,Avery,Robins
, p. 121 - 128 (1990)
A number of 6-sulfenamide, 6-sulfinamide, and 6-sulfonamide derivatives of 2-aminopurine and certain related purine ribonucleosides have been synthesized and evaluated for antileukemic activity in mice. Amination of 6-mercaptopurine ribonucleiside (7a) and 6-thioguanosine (7b) with chloramine solution gave 9-β-D-ribofuranosylpurine-6-sulfenamide (8a) and 2-amino-9-β-D-ribofuranosylpurine-6-sulfenamide-sulfenosine, 8b), respectively. Selective oxidation of 8a and 8b with 3-chloroperoxybenzoic acid (MCPBA) gave (R,S)-9-β-D-ribofuranosylpurine-6-sulfinamide (9a) and (R,S)-2-amino-9-β-D-ribofuranosylpurine-6-sulfinamide (sulfinosine, 9b), respectively. However, oxidation of 8a and 8b with excess of MCPBA gave 9-β-D-ribofuranosylpurine-6-sulfonamide (10a) and 2-amino-9-β-D-ribofuranosylpurine-6-sulfonamide (sulfonosine, 10b), respectively. Similarly, amination of 5'-deoxy-6-thioguanosine (7c) afforded the 6-sulfenamide derivative (8c), which on controlled oxidation gave (R,S)-2-amino-9-(5-deoxy-β-D-ribofuranosyl)purine-6-sulfinamide (9c) and the corresponding 6-sulfonamide derivative (10c). Treatment of 6-thioguanine (12) with aqueous chloramine solution gave 2-amino-9H-purine-6-sulfenamide (13). Oxidation of 13 with 1 molar equiv of MCPBA afforded (R,S)-2-amino-9H-purine-6-sulfinamide (14), whereas the use of 4 molar equiv of MCPBA furnished 2-amino-9H-purine-6-sulfonamide (15). The resolution of R and S diastereomers of sulfinosine (9b) was accomplished by HPLC techniques. The structures of (R)-9b and 10b were assigned by single-crystal X-ray diffraction studies. (R)-9b exists in the crystal structure in four crystallographically independent conformations. Of the 18 compounds evaluated, 13 exhibited very significant anti-L1210 activity in mice. Sulfenosine (8b) at 22 mg/kg per day x 1 showed a T/C of 170, whereas sulfinosine (9b) at 173 mg/kg per day x 1 showed a T/C of 167 against L1210 leukemia. The 5'-deoxy analogue of sulfinosine (9c) at 104 mg/kg per day also showed a T/C of 167 against L1210 leukemia. The 5'-deoxy analogue of sulfinosine (9c) at 104 mg/kg per day also showed a T/C of 172. A single treatment with 8b, 9b, and 9c reduced body burdens of viable L1210 cells by more than 99.8%.
