TY - JOUR
T1 - 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
AU - Ramasamy, Kandasamy
AU - Imamura, Nobutaka
AU - Hanna, Naeem B.
AU - Finch, Rick A.
AU - Avery, Thomas L.
AU - Robins, Roland K.
AU - Revankar, Ganapathi R.
PY - 1990/4
Y1 - 1990/4
N2 - 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-β-D-ribofuranosylpyrrolo[2,3-d]pyrimidine-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-ribofuranosylpyrrolo[2,3-d]pyrimidine-4-sulfinamide (7-deazasulfinosine, 6a) and its 2'-deoxy derivative (6c). A similar amination of 7-(2-deoxy-β-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-β-D- eryf/iro-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-l-β-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 ≥ 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%.
AB - 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-β-D-ribofuranosylpyrrolo[2,3-d]pyrimidine-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-ribofuranosylpyrrolo[2,3-d]pyrimidine-4-sulfinamide (7-deazasulfinosine, 6a) and its 2'-deoxy derivative (6c). A similar amination of 7-(2-deoxy-β-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-β-D- eryf/iro-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-l-β-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 ≥ 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%.
UR - http://www.scopus.com/inward/record.url?scp=0025257038&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025257038&partnerID=8YFLogxK
U2 - 10.1021/jm00166a021
DO - 10.1021/jm00166a021
M3 - Article
C2 - 2319564
AN - SCOPUS:0025257038
SN - 0022-2623
VL - 33
SP - 1220
EP - 1225
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 4
ER -