Synthesis, Crystal Structure, and Rotational Energy Profile of 3-Cyclopropyl-1,2,4-benzotriazine 1,4-Di-N-oxide

Abstract

1,2,4-Benzotriazine 1,4-di-N-oxides are potent antitumor drug candidates that undergo in vivo bioreduction leading to selective DNA damage in the low oxygen (hypoxic) cells found in tumors. Tirapazamine (TPZ) is the lead compound in this family. Here we report on the synthesis, crystal structure, and conformational analysis of a new analog, 3-cyclopropyl-1,2,4-benzotriazine 1,4-di-N-oxide (3). Compound 3 (C10H10N3O2) crystallized in the monoclinic space group C2/c. Unit cell parameters for 3: a = 16.6306 (12), b = 7.799 (5), c = 16.0113 (11) Å, α = 90, β = 119.0440 (10), γ = 90, and z = 8.

[3+3] Cycloadditions of Azomethine Ylides with Nitrile Imines for the Synthesis of 2,3,4,5‐Tetrahydro‐1,2,4‐Triazine‐5‐Carboxylates

“…[4] Dihydromethyl furalazine showed a wide spectrum of antibacterial activity against various pathogenic organisms, both Gram-positive and Gramnegative. [5] Cyclic amidoxime derivatives are anticoagulants for inhibiting clotting factor Xa and used for the treatment of thromboembolism. [6] Considering these activity investigations, the synthesis of 1,2,4-triazine units has attracted increasing attention of many pharmaceutical and medicinal scientists.…”

“… [3] Azaribine, an anti‐metabolite, is a prodrug for 6‐azauridine and is utilized for treatment of mycosis fungoides and psoriasis [4] . Dihydromethyl furalazine showed a wide spectrum of antibacterial activity against various pathogenic organisms, both Gram‐positive and Gram‐negative [5] . Cyclic amidoxime derivatives are anticoagulants for inhibiting clotting factor Xa and used for the treatment of thromboembolism [6] .…”

Synthesis and anticancer evaluation of some novel pyrimido[5,4-e][1,2,4]triazines and pyrazolo[3,4-d]pyrimidine using DMF-DMA as methylating and cyclizing agent

“…6-Azacytosine and 6-azauracil are used as effective antiviral and antitumor activities [ 18 – 21 ]. The tirapazamine (TPZ) is efficacious in the treatment of different human cancer cells via inducing DNA damage in poorly oxygenated tumor cells [ 22 ]. …”