Synthesis of 1-alkoxy-3-methyl-1-triazene 2-oxides and 3, 3´-methylene-bis(1-alkoxy-3-methyl-1-triazene 2-oxides)

Smirnov, G. A.; Gordeev, P. B.; Никитин, С. В.; Pokhvisneva, G. V.; Ternikova, T. V.; Luk’yanov, O. A.

doi:10.1007/s11172-015-1212-z

Cited by 11 publications

(2 citation statements)

References 14 publications

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“…The combined organic layers were washed with brine (20 mL), dried over Mg 2 SO 4 , and evaporated under vacuum. The crude product was purified by flash chromatography on silica gel by using EA and hexane for eluting to give target compounds 12 and 13 …”

Section: Methodsmentioning

confidence: 99%

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General Strategy for Integrated Bioorthogonal Prodrugs: Pt(II)-Triggered Depropargylation Enables Controllable Drug Activation In Vivo

Sun

et al. 2020

J. Med. Chem.

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Bioorthogonal decaging reactions for controllable drug activation within complex biological systems are highly desirable yet extremely challenging. Herein, we find a new class of Pt(II)-triggered bioorthogonal cleavage reactions in which Pt(II) but not Pt(IV) complexes effectively trigger the cleavage of O/Npropargyl in a variety of ranges of caged molecules under biocompatible conditions. Based on these findings, we propose a general strategy for integrated bioorthogonal prodrugs and accordingly design a prodrug 16, in which a Pt(IV) moiety is covalently connected with an O 2 -propargyl diazeniumdiolate moiety. It is found that 16 can be specifically reduced by cytoplasmic reductants in human ovarian cancer cells to liberate cisplatin, which subsequently stimulates the cleavage of O 2 -propargyl to release large amounts of NO in situ, thus generating synergistic and potent tumor suppression activity in vivo. Therefore, Pt(II)-triggered depropargylation and the integration concept might provide a general strategy for broad applicability of bioorthogonal cleavage chemistry in vivo.

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Section: Methodsmentioning

confidence: 99%

“…The crude product was purified by flash chromatography on silica gel by using EA and hexane for eluting to give target compounds 12 26 and 13. 59 O 2 -Propargyl 1-(N-Methylethanolamine-N-yl)-diazen-1-ium-1,2diolate (12). Colorless oil, 562 mg, yield 51%.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%