Efficient Multicomponent Reaction Synthesis of the Schistosomiasis Drug Praziquantel

Cao, Haiping; Liu, Haixia; Dömling, Alexander

doi:10.1002/chem.201002046

Cited by 85 publications

(67 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The 10-methoxy-substituted PZQ 14 , the common intermediate in preparing all target compounds, was obtained from 12 by the same stepwise Ugi four-component reaction and Pictect–Spengler reaction used by Cao et al to prepare PZQ from 2-phenylethanamine. 23 Briefly, a mixture of paraformaldehyde, dimethoxyethylamine and cyclohexylcarboxylic acid in methanol was treated with 12 to give 13 (Ugi reaction). This intermediate was added to methanesulfonic acid to afford 17 (Pictect-Spengler reaction).…”

Section: Resultsmentioning

confidence: 99%

New praziquantel derivatives containing NO-donor furoxans and related furazans as active agents against Schistosoma mansoni

Guglielmo

Cortese

Vottero

et al. 2014

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

A series of NO-donor praziquantel hybrid compounds was obtained by combining praziquantel (PZQ) and furoxan moieties in a single entity. NO-donor properties of the furoxan derivatives were evaluated by detecting nitrite after incubation of the products in 7.4 pH buffered solution in the presence of L-cysteine. Structurally-related furazans, devoid of NO release capacity, were also synthesized for control purposes. All products were studied for their ability to inhibit recombinant Schistosoma mansoni thioredoxin glutathione reductase (TGR). Mobility and death of adult Schistosoma mansoni worms cultured in the presence of the products were evaluated versus PZQ. Analysis of the results showed that some products were endowed with both PZQ and NO-dependent antiparasitic properties. Compounds 6, 7, 18, and 24 emerged as the most interesting balanced hybrids, worthy of additional study on PZQ-resistant parasites.

show abstract

Section: Resultsmentioning

confidence: 99%

New praziquantel derivatives containing NO-donor furoxans and related furazans as active agents against Schistosoma mansoni

Guglielmo

Cortese

Vottero

et al. 2014

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…[56] Clearly, more synthetic targets are out there, which can be potentially accessed in a more convergent and cheaper way using MCR chemistry, thus potentially benefiting the patient.…”

Section: Applications In the Pharmaceutical And Agrochemical Industriesmentioning

confidence: 99%

Multicomponent Reactions, Union of MCRs and Beyond

Zarganes‐Tzitzikas

Chandgude

Dömling

2015

The Chemical Record

Self Cite

244

142

View full text Add to dashboard Cite

Multicomponent reactions (MCRs), which are located between one- and two-component and polymerization reactions, provide a number of valuable conceptual and synthetic advantages over stepwise sequential approaches towards complex and valuable molecules. To address current limitations in the number of MCRs and the resulting scaffolds, the concept of union of MCRs was introduced two decades ago by Dömling and Ugi and is rapidly advancing, as is apparent by several recently published works. MCR technology is now widely recognized for its impact on drug discovery projects and is strongly endorsed by industry in addition to academia. Clearly, novel scaffolds accessible in few steps including MCRs will further enhance the field of applications. Additionally, broad expansion of MCR applications in fields such as imaging, materials science, medical devices, agriculture, or futuristic applications in stem cell therapy and theragnostics or solar energy and superconductivity are predicted.

show abstract

“…MCRs are defined as high convergent sequentially combinations of at least three reagents in a single experimental operation and, in the same reactor, to construct diverse molecular architectures, for example, complex polyheterocycles [15]. It is noteworthy that, MCRs are robust and efficient tools useful in Diversity Oriented Synthesis (DOS) [16], Combinatorial Chemistry (CC) [17] and Target Oriented Synthesis [18]. In this context, MCRs have been used successfully to synthesize series of benzo[ f ][1,7]naphthyridine-based compounds.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi-3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization

et al. 2018

View full text Add to dashboard Cite

A series of eight new 5-aryl-benzo[f][1,7]naphthyridines were synthesized in 17 to 64% overall yields via an improved MW-assisted cascade-like one pot process (Ugi–three component reaction/intramolecular aza-Diels-Alder cycloaddition) coupled to an aromatization process from tri-functional dienophile-containing ester-anilines, substituted benzaldehydes and the chain-ring tautomerizable 2-isocyano-1-morpholino-3-phenylpropan-1-one as starting reagents, under mild conditions. The doubly activated dienophile and the aza-diene functionalities of the eight new Ugi-adducts were exploited to perform an in situ aza-Diels-Alder cycloaddition/aromatization (dehydration/oxidation) process, toward the complex polysubstituted 5-aryl-polyheterocycles, which could be taken as starting point for further SAR studies because the benzo[f][1,7]naphthyridine is the core of various bioactive products. It is relevant to emphasize that the synthesis or isolation of benzo[f][1,7]naphthyridines containing a substituted aromatic ring in the C-5 position, has not been published before.

show abstract

Efficient Multicomponent Reaction Synthesis of the Schistosomiasis Drug Praziquantel

Abstract: Shorter than ever: A convergent, efficient, and scalable access based on a key Ugi four‐component reaction (4CR) followed by a Pictet–Spengler reaction comprises the shortest known synthesis to the schistosomiasis drug praziquantel (see scheme).

Cited by 85 publications

References 24 publications

New praziquantel derivatives containing NO-donor furoxans and related furazans as active agents against Schistosoma mansoni

New praziquantel derivatives containing NO-donor furoxans and related furazans as active agents against Schistosoma mansoni

Multicomponent Reactions, Union of MCRs and Beyond

Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi-3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization

Contact Info

Product

Resources

About