Three component Kabachnik-Fields condensation leading to substituted aminomethane-P-hydroxymethylphosphonic acids as a tool for screening of bacterial urease inhibitors

Vassiliou, Stamatia; Grabowiecka, Agnieszka; Kosikowska, Paulina; Berlicki, Łukasz

doi:10.3998/ark.5550190.0013.404

Cited by 8 publications

(8 citation statements)

References 11 publications

(12 reference statements)

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“…Alternatively, the use of hydroxamic acids is restricted by their side effects, with teratogenicity being the most serious. , Nevertheless, acetohydroxamic acid was introduced to the market for the treatment of chronic infections of the urinary tract. We have focused on exploration of the N–C–P structural motif for the development of urease inhibitors (Figure ). − …”

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confidence: 99%

“…These studies resulted in a highly potent compound ( 5 ) with a K i = 0.36 μM against urease from Proteus vulgaris . Interestingly, various other modifications, such as elongation of the amino group substituents or substitution of the hydroxymethyl moiety, led to a substantial decrease in activity . Thus, we decided to apply a new backbone that can be modified in multiple positions.…”

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Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors

Macegoniuk

Dziełak

Mucha

et al. 2014

ACS Med. Chem. Lett.

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Inhibitors of bacterial ureases are considered to be promising compounds in the treatment of infections caused by Helicobacter pylori in the gastric tract and/or by urealytic bacteria (e.g., Proteus species) in the urinary tract. A new, extended transition state scaffold, bis(aminomethyl)phosphinic acid, was successfully explored for the construction of effective enzyme inhibitors. A reliable methodology for the synthesis of phosphinate analogues in a three-component Mannich-type reaction was elaborated. The obtained molecules were assayed against ureases purified from Sporosarcina pasteurii and Proteus mirabilis, and aminomethyl(N-n-hexylaminomethyl)phosphinic acid was found to be the most potent inhibitor, with a K i = 108 nM against the S. pasteurii enzyme.

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Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors

Macegoniuk

Dziełak

Mucha

et al. 2014

ACS Med. Chem. Lett.

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“…It is instructive to compare different methods for production of secondary amines. For example, N-benzylcyclohexylamine, which is an intermediate for synthesis of pharmaceuticals, [89] can be prepared via reductive amination of cyclohexanone with benzylamine in hydrogen, [10] or alternatively using NaBH 4 as a reductant over solid carbon catalyst (Table 6). [12] The third method is to use formic acid as a reducing agent together with Au/TiO 2 , [13] acidic ionic liquid supported on silica [14] or sulfonic acid supported on hydroxyapatite encapsulated γ-Fe 2 O 3 [γ-Fe 2 O 3 @HAP-SO 3 H].…”

Section: Comparison Of Different Methods To Synthesize Secondary Aminesmentioning

confidence: 99%

One-pot amination of aldehydes and ketones over heterogeneous catalysts for production of secondary amines

2021

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This review summarizes the recent studies on the synthesis of secondary amines by one-pot amination of aldehydes and ketones over heterogeneous catalysts. Amines are widely applied as the key intermediates in chemical industry for the synthesis of various commodities such as agrochemicals, drugs, detergents, lubricants, food-additives and polymers. Direct catalytic reductive amination of carbonyl compounds was considered which generally includes two steps: (i) formation of imines by interactions of aldehydes or ketones with amines, and (ii) subsequent hydrogenation of imines. Synthesis of secondary amines from carbonyl compounds and amines generated in situ under reaction conditions from their progenitors, e.g., respectively, alcohols or nitro-compounds, is also discussed in detail. Recent progress in application of hydrogen sources alternative to gaseous H 2 , such as formic acid, NaBH 4 , CO and water, favored development of metal-free catalysts including solid acid catalysts. The review addresses the scope of the amination reaction with aldehydes/ketones and nitro/amine compounds of different structure, the effect of the solvent, reaction conditions and catalyst properties. In addition, catalyst regeneration and reuse, kinetic regularities and kinetic modeling with an emphasis on the continuous mode of one-pot amination have been systematically summarized and discussed. It is suggested that the future work should focus on revealing the role of the catalytically active sites addressing their acid-base properties and the correlation between catalyst properties and the reaction performance, elucidating kinetic parameters and designing feasible reactor system for further industrial implementation.

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“…Generally, methylation of amino compounds can be achieved by nucleophilic substitution reactions with methyl iodide 12 or by reductive amination with aldehydes. 13,14 Therefore, the deuterated methylation of amino compounds can be achieved with deuterated methylating agents such as deuteroiodomethane and TsOCD 3 . 15 However, the purity of the nucleophilic substitution reaction between the amine and deuteroiodomethane is relatively low due to the high activity of deuteroiodomethane.…”

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confidence: 99%

A practical synthesis of deuterated methylamine and dimethylamine

Liu

Ren

Wang

2020

Journal of Chemical Research

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In recent years, several deuterated drugs have entered clinical trials and have been approved for use. Deuterated methylamine and dimethylamine as important intermediates play significant roles in the preparation of deuterated drugs. In this study, we have developed a new method to prepare deuterated methylamine and dimethylamine. This method employs Boc-benzylamine as the starting material and TsOCD3 as the deuterated methylation reagent. Our method gives relatively high yields and involves simple purifications, which provide a favourable supplement for the development and synthesis of deuterated drugs in the future.

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Three component Kabachnik-Fields condensation leading to substituted aminomethane-P-hydroxymethylphosphonic acids as a tool for screening of bacterial urease inhibitors

Cited by 8 publications

References 11 publications

Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors

Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors

One-pot amination of aldehydes and ketones over heterogeneous catalysts for production of secondary amines

A practical synthesis of deuterated methylamine and dimethylamine

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