Solid-Phase Synthesis of Urea and Amide Libraries Using the T2 Triazene Linker

Bräse, Stefan; Dahmen, Stefan; Pfefferkorn, Marc

doi:10.1021/cc000051s

Cited by 80 publications

(41 citation statements)

References 24 publications

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“…In organic synthesis, they have been used as protecting groups for aromatic amines, as linkers in solid-phase peptide synthesis and as synthons for novel heterocyclic compounds [4][5][6]. Triazenes have also been investigated as antitumor agents and incorporated into novel conductive aromatic polymers [7,8].…”

Section: Introductionmentioning

confidence: 99%

The synthesis, X‐ray structure analysis, and photophysical characterization of 4‐[(E)‐2‐(4‐cyanophenyl)diazenyl]‐morpholine

Chin

Phipps

Fronczek

et al. 2010

Journal of Heterocyclic Chem

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A novel triazene, 4-[(E)-2-(4-cyanophenyl)diazenyl]-morpholine (1) was prepared via a diazonium ion coupling reaction between 4-aminobenzonitrile and morpholine. The x-ray structure of 1 was determined and evidenced p delocalization in the triazene subunit. The room temperature absorption spectrum of 1 in acetonitrile was dominated by an intense triazene-centered p!p* transition at 325 nm. Compound 1 was observed to be luminescent, with an emission maximum at 434 nm in room temperature acetonitrile solution. The emission spectrum of 1 in propionitrile glass at 77K exhibited a narrowed emission band with a maximum at 449 nm. Broad emission from 400-700 nm with poorly resolved vibrational structure was observed from solid 1 at room temperature.

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Section: Introductionmentioning

confidence: 99%

The synthesis, X‐ray structure analysis, and photophysical characterization of 4‐[(E)‐2‐(4‐cyanophenyl)diazenyl]‐morpholine

Chin

Phipps

Fronczek

et al. 2010

Journal of Heterocyclic Chem

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“…Urea derivatization was performed with H-Phe(4-N,Ndimethylphenylamine)-Rink amide resin, which was used in the validation and in the preproduction of the library, and 4 equiv of cyclohexylisocyanate in DCM for 4 h at 25 8C [15]. The final product was obtained in 69% purity and 85% yield (Scheme 6).…”

Section: Full Papersmentioning

confidence: 99%

Solid-Phase Preparation of a Library Based on a Phenylalanine Scaffold

et al. 2005

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A convenient strategy (preliminary study, preproduction and production) for the solidphase preparation of a library using 4-iodophenylalanine as a scaffold is described. The aromatic ring was first modified via the Suzuki reaction and the amino position was subsequently derivatized into amides, sulfonamides, amines, carbamates and ureas. The scope and limitations of all of the reactions carried out in parallel are discussed. The solid-phase synthesis of a library of 315 individual compounds was attempted by using seven boronic acids and nine representative compounds from each of the following classes: carboxylic acids, sulfonyl chlorides, aldehydes, alcohols and isocyanates. Owing to the failure of the amine derivatization, 297 compounds were ultimately obtained.

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“…They have diverse applications as DNA alkylating agents in tumor therapy, protecting groups in natural product synthesis and combinatorial chemistry, as well as precursors incorporated into polymer and oligomer synthesis. [2][3][4][5][6][7][8] Hydrolysis of DNA or RNA catalyzed by relevant enzymes is an important subject in biotechnology, medicine and drug development. 9,10 Synthetic nucleases which rapidly cleave nucleic acids under mild conditions have many important potential applications ranging from the synthesis of custom-designed artificial restriction enzymes to the development of new antitumor agents.…”

Section: Introductionmentioning

confidence: 99%

In vitro evaluation of triazenes: DNA cleavage, antibacterial activity and cytotoxicity against acute myeloid leukemia cells

Domingues

Hörner

Reetz

et al. 2010

J. Braz. Chem. Soc.

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triazeno (3) foram avaliadas quanto à capacidade de clivagem do DNA plasmidial pUC18 e pBSKII, atividade antibacteriana e citotoxicidade in vitro frente a células de leucemia mielóide aguda e leucócitos normais utilizando o bioensaio da redução do sal brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT). Os triazenos analisados demonstraram capacidade de clivagem dos dois tipos de DNA plasmidial: triazeno 1 em pH 8,0 e 50 °C; triazeno 2 em pH 6,5 a 37 e 50 °C; triazeno 3 em pH 6,5 e 37 °C. Os compostos apresentaram atividade citotóxica frente a células leucêmicas. O composto 1 mostrou alta atividade frente a B. cereus (CIM = 32 mg mL -1 ). A associação molecular através de ligações de hidrogênio no estado sólido do composto 3 com base na análise estrutural por difratometria de raios X em monocristal, bem como os resultados das análises espectroscópicas nas regiões do IV e UV-Vis dos compostos 1, 2 e 3 são discutidos no presente trabalho.The asymmetric diazoamines 1-(2-chlorophenyl)-3-(4-carboxyphenyl)triazene (1), 1-(2-fluorophenyl)-3-(4-carboxyphenyl)triazene (2) and 1-(2-fluorophenyl)-3-(4-amidophenyl) triazene (3) were evaluated for their ability to cleave pUC18 and pBSKII plasmid DNA, antibacterial activity and in vitro cytotoxicity against acute myeloid leukemia cells and normal leukocytes using the bioassay of reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The triazenes showed ability to cleave the two types of plasmid DNA: triazene 1 at pH 8.0 and 50 °C; triazene 2 at pH 6.5 and 37 and 50 °C; triazene 3 at pH 6.5 and 37 °C. The compounds presented cytotoxic activity against myeloid leukemia cells. Compound 1 showed high activity against B. cereus (MIC = 32 mg mL -1 ). The observation of intermolecular hydrogen bonding in the solid state of compound 3, based on the structural analysis by X-ray crystallography, as well as the results of IR and UV-Vis spectroscopic analyses of compounds 1, 2 and 3 are discussed in the present work.Keywords: triazenes, DNA cleavage, antibacterial activity, cytotoxicity IntroductionTriazenes or diazoamines constitute a class of compounds containing three consecutive nitrogen atoms in an acyclic arrangement. 1 Diazoamino compounds can be obtained by diverse synthetic ways, the classical method including the coupling reaction of a diazonium salt, [R-N≡N] + X -, with an amine (R'-NH 2 ) in acidic medium. This is followed by formation of the respective diazoamino compound R-N=N-N(H)-R' (R = R' for Domingues et al. 2227 Vol. 21, No. 12, 2010 symmetric triazenes; R ≠ R' for asymmetric compounds) by stepwise neutralization of the reaction system. They have diverse applications as DNA alkylating agents in tumor therapy, protecting groups in natural product synthesis and combinatorial chemistry, as well as precursors incorporated into polymer and oligomer synthesis. [2][3][4][5][6][7][8] Hydrolysis of DNA or RNA catalyzed by relevant enzymes is an important subject in biotechnology, medicine and drug development. 9,10 Synthetic nuclease...

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Solid-Phase Synthesis of Urea and Amide Libraries Using the T2 Triazene Linker

Cited by 80 publications

References 24 publications

The synthesis, X‐ray structure analysis, and photophysical characterization of 4‐[(E)‐2‐(4‐cyanophenyl)diazenyl]‐morpholine

The synthesis, X‐ray structure analysis, and photophysical characterization of 4‐[(E)‐2‐(4‐cyanophenyl)diazenyl]‐morpholine

Solid-Phase Preparation of a Library Based on a Phenylalanine Scaffold

In vitro evaluation of triazenes: DNA cleavage, antibacterial activity and cytotoxicity against acute myeloid leukemia cells

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