Synthesis and Evaluation of Anthelmintic and Cytotoxic Properties of Bis- 1,3-Azole Analogs of Natural Products

Sellanes, Diver; Scarone, Laura; Mahler, Graciela; Manta, Eduardo; Baz, Ahsene; Dematteis, Sylvia; Saldaña, Jenny; Domínguez, Laura; Wipf, Peter; Serra, Gloria

doi:10.2174/157018006775240962

Cited by 8 publications

(5 citation statements)

References 1 publication

(1 reference statement)

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“…Bengazole and mycothiazole analogues, such as compounds 11 and 12 , were reported by Manta et al [29,30] These derivatives were found to have in vitro Nippostrongylus brasiliensis activity similar to bengazole and mycothiazole whilst being more chemically stable than the parent analogues. …”

Section: Recent Patent Landscape: New Antiparasitic Compoundsmentioning

confidence: 95%

Anthelmintic discovery and development in the animal health industry

Woods

Lauret

Geary

2007

Expert Opinion on Drug Discovery

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Most modern anthelmintics used against human pathogens have come from the animal health (AH) industry. Historically, new molecules were discovered empirically, but recent developments in genomic and screening technologies have significantly enhanced the opportunities for target-based identification of novel therapies. However, drug discovery and development is still a complicated and costly process with high attrition. Absence of a return in investment for tropical parasitic diseases makes it difficult for large pharmaceutical companies to justify seeking antiparasitics for less developed countries in isolation. A partnership in which there is a sharing of costs and leveraging of resources is one way forward and is reflected in the new paradigm of 'integrated drug discovery', where collaborations and networks of academic institutions and industry are working together towards the discovery of new treatments for tropical parasitic diseases.

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Section: Recent Patent Landscape: New Antiparasitic Compoundsmentioning

confidence: 95%

Anthelmintic discovery and development in the animal health industry

Woods

Lauret

Geary

2007

Expert Opinion on Drug Discovery

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“…38,39 Furthermore, some thioformamides show antifungal 40 and antibacterial activity, 41 and they have been employed in the synthesis of thiazoles via the Hantzsch protocol. 42 We envisaged the use of Nurethane-protected amino alkyl thioformamides for the synthesis of the corresponding isonitriles through a dehydrosulfurization reaction.…”

Section: Methodsmentioning

confidence: 99%

“…Sulfur-containing compounds such as thioamides and thioesters have been found to be better reactants in the preparation of several heterocycle-tethered peptidomimetics and other related compounds compared to their oxygenated analogues. 38,39 Furthermore, some thioformamides show antifungal 40 and antibacterial activity, 41 and they have been employed in the synthesis of thiazoles via the Hantzsch protocol. 42 We envisaged the use of Nurethane-protected amino alkyl thioformamides for the synthesis of the corresponding isonitriles through a dehydrosulfurization reaction.…”

Section: Methodsmentioning

confidence: 99%

Cyanogen Bromide as Dehydrosulfurizing Agent for the Synthesis of Nβ-Fmoc-Amino Alkyl Isonitriles from Nβ-Fmoc-Amino Alkyl Thioformamides

Vishwanatha¹,

Hemantha²,

Sureshbabu³

2010

Synlett

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Synthetically useful N b -Fmoc amino alkyl isonitriles are prepared conveniently from N b -Fmoc amino alkyl thioformamides via a cyanogen bromide mediated dehydrosulfurization. The reaction is fast, clean, and yields are good.Key words: N b -Fmoc-amino alkyl thioformamides, isonitriles, dehydrosulfurization, cyanogen bromideIn recent years, the synthetic utility of isonitriles 1 in organic reactions has been exploited. Compounds containing an isocyano group find use as antibiotics, 2 antineoplastics, 3 and antianaesthetics. 4 The synthetic utility of isonitriles arises from their divergent character 5 and this functionality has wide utility, such as in the preparation of isothiocyanates, 6 N,N-dialkylcarbodiimides, 7 1-substituted tetrazoles, 8 [16][17][18][19][20] has been well demonstrated.In peptide chemistry, the application of isonitrile derivatives of amino acids has led to a variety of peptidomimetics 21 and other useful products such as blactams, 22 glycopeptides, 23 depsipeptides, 24 peptide nucleic acids, 25 and N-hydroxy peptides. 26 Amino acid ester derived isonitriles are the known entities, which are prepared from corresponding formyl amino acid esters. 27A recent entry into this new class of amino acid derived isonitriles has been described by our group wherein N bFmoc amino alkyl isonitriles were obtained through carboxyl group modification. 28Of the many methods available for the preparation of isonitriles, dehydration of formamides is the widely followed route in amino acid chemistry, showing general applicability and reproducibility. 29 Reaction of alkyl halides with heavy metal cyanide salts, 30 addition of dichlorocarbene to amines, 31 reduction of isocyanates and isothiocyanates 32 are other available routes. Dehydration of formamides has been carried out by using tosyl chloride, phosphorus oxychloride (POCl 3 ) in the presence of a base, cyanuric chloride, triphenyl phosphine-CCl 4 , phosgene, diphosgene, and triphosgene. 33 The method employing POCl 3 being quite harsh is found to cause racemization and therefore is not applicable in peptide chemistry, and isolation of enantiomerically pure isonitriles is always challenging and demanding. Danishefsky and co-workers have isolated enantiomerically pure aisocyanoesters 34 derived from formyl amino acid esters, employing triphosgene/N-methylmorpholine (NMM) at -78°C. Nenajdenko's group has synthesized the amino acid derived nonracemic isonitriles employing the less commonly used 4-methyl-2,6,7-trioxabicyclo[2.2.2] octyl-protected formyl amino ester.35 Sureshbabu et al. reported the synthesis and isolation of enantiomerically pure N-Fmoc-amino alkyl isonitriles by the dehydration of the corresponding N b -Fmoc amino alkyl formamides under neutral conditions employing Burgess' reagent.28 In a continuation of our current studies on isonitriles, we sought a simple and economically viable route involving dehydrosulfurization of N b -Fmoc amino alkyl thioformamides using cyanogen bromide (CNBr, Scheme 1). Scheme 1There has been a sur...

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“…Molecules having pyrimidine as a core unit exhibit various biological activities such as antiviral , antibacterial , antitumor , anti‐inflammatory , and antifungal . Oxazoles are well‐known common motifs in natural products including phenoxan , noricumazoles , hennoxazoles , and leiodolides A and B , and many of them possess significant antimicrobial , cytotoxic , and anthelmintic activities. Thiazole derivatives are important components in medicinal chemistry because of their broad applications in drug development as antiviral , anticancer , antibacterial , antifungal , and anti‐inflammatory agents.…”

Section: Introductionmentioning

confidence: 99%