1-Methylpyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones 4, synthesized in good to excellent yields, were designed as novel alkylating agents because of their peculiar chemical behavior. All derivatives showed antiproliferative activity against more than 50 types of tumor cell lines with GI50 reaching sub-micromolar values. SAR studies revealed that the presence of a chlorine atom is well-tolerated in both positions 8 and 9, whereas in the case of the methyl group, switching from the 8 to the 9 position gives rise to the most active compound of the series, 4g, either for the number of cell lines inhibited and for selectivity against leukaemia and renal cancer subpanels. COMPARE and 3D-MIND computations indicate, for compounds 4, an activity profile analogous to rifamycins and cytidine analogues.

ALMERICO AM, MINGOIA F, DIANA P, BARRAJA P, LAURIA A, MONTALBANO A, et al. (2005). 1-Methyl-3H-pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones. Design, Synthesis, and Biological Activity of New Antitumor Agents. JOURNAL OF MEDICINAL CHEMISTRY, 48(8), 2859-2866 [10.1021/jm049075u].

1-Methyl-3H-pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones. Design, Synthesis, and Biological Activity of New Antitumor Agents

ALMERICO, Anna Maria;DIANA, Patrizia;BARRAJA, Paola;LAURIA, Antonino;MONTALBANO, Alessandra;CIRRINCIONE, Girolamo;DATTOLO, Gaetano
2005-01-01

Abstract

1-Methylpyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones 4, synthesized in good to excellent yields, were designed as novel alkylating agents because of their peculiar chemical behavior. All derivatives showed antiproliferative activity against more than 50 types of tumor cell lines with GI50 reaching sub-micromolar values. SAR studies revealed that the presence of a chlorine atom is well-tolerated in both positions 8 and 9, whereas in the case of the methyl group, switching from the 8 to the 9 position gives rise to the most active compound of the series, 4g, either for the number of cell lines inhibited and for selectivity against leukaemia and renal cancer subpanels. COMPARE and 3D-MIND computations indicate, for compounds 4, an activity profile analogous to rifamycins and cytidine analogues.
2005
ALMERICO AM, MINGOIA F, DIANA P, BARRAJA P, LAURIA A, MONTALBANO A, et al. (2005). 1-Methyl-3H-pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-ones. Design, Synthesis, and Biological Activity of New Antitumor Agents. JOURNAL OF MEDICINAL CHEMISTRY, 48(8), 2859-2866 [10.1021/jm049075u].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/11847
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