Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity

Proteau-Gagné, Arnaud; Rochon, Kristina; Roy, Mélissa; Albert, Pierre-Julien; Guérin, Brigitte; Gendron, Louis; Dory, Yves L.

doi:10.1016/j.bmcl.2013.08.020

Cited by 26 publications

(25 citation statements)

References 26 publications

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“…Carpino and El‐Faham had demonstrated the influence of solvent and base on the preactivation rate of amino acids with DIC/HOAt (DIC= N , N ′‐diisopropylcarbodiimide) and suggested to use a base‐free preactivation in DCM, instead of DMF . The problem of possible epimerization during the coupling of triazole dipeptide‐isosteric building blocks was also reported for 1,4‐disubstituted triazoles . Horne et al.…”

Section: Resultsmentioning

confidence: 98%

1,5‐Disubstituted 1,2,3‐Triazole‐Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Kracker

Góra

Krzciuk-Gula

et al. 2017

Chemistry A European J

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Peptidotriazolamers are hybrid foldamers combining features of peptides and triazolamers-repetitive peptidomimetic structures with triazoles replacing peptide bonds. We report on the synthesis of a new class of peptidomimetics, containing 1,5-disubstituted 1,2,3-triazoles in an alternating fashion with amide bonds and the analysis of their conformation in solid state and solution. Homo- or heterochiral peptidotriazolamers were obtained from enantiomerically pure propargylamines with stereogenic centers in the propargylic position and α-azido esters by ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave conditions in high yields. With such building blocks the peptidotriazolamers are readily available by solution phase synthesis. While the conformation of the homochiral peptidotriazolamer Boc-Ala[5Tz]Phe-Val[5Tz]Ala-Leu[5Tz]Val-OBzl resembles that of a β VIa1 turn, the heterochiral peptidotriazolamer Boc-d-Ala[5Tz]Phe-d-Val[5Tz]Ala-d-Leu[5Tz]Val-OBzl adopts a polyproline-like repetitive structure.

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Section: Resultsmentioning

confidence: 98%

1,5‐Disubstituted 1,2,3‐Triazole‐Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Kracker

Góra

Krzciuk-Gula

et al. 2017

Chemistry A European J

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“…These drawbacks prompted us to develop a new series of inhibitors 2 (Figure ). Our approach is based on bioisosteric replacement of the amide moiety by more drug‐like scaffolds such as azoles (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Azole‐based non‐peptidomimetic plasmepsin inhibitors

Kinena

Leitis

Kanepe

et al. 2018

Archiv der Pharmazie

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The spread of drug-resistant malaria parasites urges the search for new antimalarial drugs. Malarial aspartic proteases - plasmepsins (Plms) - are differentially expressed in multiple stages of the Plasmodium parasite's lifecycle and are considered as attractive drug targets. We report the development of novel azole-based non-peptidomimetic plasmepsin inhibitors that have been designed by bioisosteric substitution of the amide moiety in the Actelion amino-piperazine inhibitors. The best triazole-based inhibitors show submicromolar potency toward Plm II, which is comparable to that of the parent Actelion compounds. The new inhibitors can be used as a starting point for the development of a resistance-free antimalarial drug targeting the non-digestive Plm IX or X, which are essential for the malaria parasite life cycle.

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“…Therefore, in this work, we report six new analogues of Bnz ( 3–8 ), including their design, synthesis and biological evaluation. All these compounds contain a 1,2,3‐triazole ring in their structure, and the substitution of the amide functional group with a 1,2,3‐triazole ring could be justified because they present similar physicochemical properties, volume and planarity . In compound 3 , the moiety of Bnz was maintained in the structure, replacing only the amide group by a 1,2,3‐triazole ring, making compound 3 an isostere of Bnz.…”

Section: Introductionmentioning

confidence: 99%

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

et al. 2018

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Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease.

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Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity

Cited by 26 publications

References 26 publications

1,5‐Disubstituted 1,2,3‐Triazole‐Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

1,5‐Disubstituted 1,2,3‐Triazole‐Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Azole‐based non‐peptidomimetic plasmepsin inhibitors

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

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