Hi,

This reference may be of help.

Bill

Targeting enzymes with phosphonate-​based inhibitors: mimics of tetrahedral transition states and stable isosteric analogues of phosphates

By Azema, L.; Baron, R.; Ladame, S.

From Current Enzyme Inhibition (2006), 2(1), 61-72. | Language: English,

A review. Phosphorus plays a fundamental role in cell since it is a part of many biomols. and biol. metabolites which include phospholipids, nucleic acids, proteins, polysaccharides or nucleotide cofactors. Phosphorus is most commonly found under its highest oxidized state as in orthophosphate or phosphate esters. However, there are also examples of naturally occurring mols. bearing phosphorus atoms at lower oxidized state that contain one carbon to phosphorus (P-​C) bond. These compds., so-​called phosphonates, are much more resistant to chem. and enzymic hydrolysis, thermal decompn. and ph...

Hi, William

Thanks for the article.. I have already gone through that and It is not getting any difference between the use of carboxylic acid ester and phosphonate ester against Trypanosomiasis....

But you diserve big thank you for your attempt.

Hi,

Maybe the papers which cited this one could be of help. See Below

Bill

Papers which cited

Targeting enzymes with phosphonate-based inhibitors: mimics of tetrahedral transition states and stable isosteric analogues of phosphates

Azema, L.; Baron, R.; Ladame, S.

Current Enzyme Inhibition (2006), 2(1), 61-72. | Language: English,

Frings, M.a , Thomé, I.a , Schiffers, I.a , Pan, F.b , Bolm, C.a

Catalytic, asymmetric synthesis of phosphonic γ-(hydroxyalkyl) butenolides with contiguous quaternary and tertiary stereogenic centers

(2014) Chemistry - A European Journal, 20 (6), pp. 1691-1700. Cited 1 time.

a Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany

b Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany

Abstract

A procedure that enables high yielding access to phosphonic γ-(hydroxyalkyl)butenolides with excellent regio-, diastereo- and enantiocontrol is reported. The simultaneous construction of up to two adjacent quaternary stereogenic centers by a catalytic asymmetric vinylogous Mukaiyama aldol reaction unites biologically and medicinally relevant entities, namely α-hydroxy phosphonates and γ-(hydroxyalkyl)butenolides. This is achieved by utilizing a readily available chiral copper-sulfoximine catalyst showing a broad functional group tolerance for both the electrophilic and nucleophilic reactants. A discussion about potential factors affecting the observed level of enantioselectivity, which stems from the enantiopure sulfoximine ligand, is also included. Best of two worlds: A chiral copper-sulfoximine catalyst unites biologically relevant α-hydroxy phosphonates and γ-(hydroxyalkyl) butenolides into one structural motif with regio-, diastereo- and enantioselectivity up to the limits of detection (see scheme; Tf=trifluoromethanesulfonyl, TMS=trimethylsilyl). Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Author Keywords

α-hydroxy phosphonates; aldol reaction; asymmetric catalysis; butenolides; sulfoximines

Document Type: Article

Source: Scopus

Kraicheva, I.a , Vodenicharova, E.a , Shivachev, B.b , Nikolova, R.b , Kril, A.c , Topashka-Ancheva, M.d , Iliev, I.c , Georgieva, A.c , Gerasimova, T.d , Tosheva, T.a , Tashev, E.a , Tsacheva, I.a , Troev, K.a

Anthracene-derived bis-aminophosphonates: Crystal structure, in vitro antitumor activity, and genotoxicity in vivo

(2013) Phosphorus, Sulfur and Silicon and the Related Elements, 188 (11), pp. 1535-1547.

a Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, 1113, Sofia, Bulgaria

b Institute of Mineralogy and Crystallography, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

c Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

d Institute of Biodiversity and Ecosystems Research, Bulgarian Academy of Sciences, 1113, Sofia, Bulgaria

Abstract

The X-ray crystal structures of the anthracene-derived bis- aminophosphonates 4.4′-bis[N-methyl(diethoxyphosphonyl)-1-(9-anthryl)] diaminodiphenylmethane (1) and 1,3-bis [N-methyl(diethoxyphosphonyl)-1-(9- anthryl)]diaminobenzene (3) are reported. The X-ray analyses demonstrated that both compounds crystallize in a centrosymmetric manner containing a meso-form (1) and a pair of enantiomers (3). The cytotoxic potential, genotoxicity, and antiproliferative activity of bis-aminophosphonates 1 and bis[N- methyl(diethoxyphosphonyl)-1-(9-anthryl)]benzidine (2), as well as their subcellular distribution in a tumor cell culture system, are also discussed. Compounds 1 and 2 showed optimal antiproliferative activity to human tumor cells from colon carcinoma line HT-29. In vitro and in vivo safety testing revealed that the compounds exert lower toxicity to normal cells as compared with well-known anticancer and cytotoxic agents. Supplemental materials are available for this article. Go to the publisher's online edition ofPhosphorus, Sulfur, and Silicon and the Related Elementsto view the free supplemental file. © 2013 Copyright Taylor and Francis Group, LLC.

Author Keywords

Aminophosphonic acids; antitumor activity; genotoxicity; in vitro cytotoxicity; single crystal

Document Type: Article

Source: Scopus

Tusek-Bozic, L.

Aminophosphonate metal complexes of biomedical potential

(2013) Current Medicinal Chemistry, 20 (16), pp. 2096-2117.

Division of Physical Chemistry, Ruder Boskovic Institute, Bijenicka 54, HR-10002 Zagreb, Croatia

Abstract

Metals and their complexes with organic ligands have an important role in biochemical systems such as enzymatic catalysis, metal ion transfer across the cell membranes, treatment of malignancy, rheumatoid arthritis, ulcer and other types of diseases. Special attention is directed to metal complexes with ligands which are important in biological systems, as their incorporation into metallo-organic compounds offers much scope for design of potential metal-based agents that provide new opportunities in the medicinal chemistry. In view of this, derivatives of aminophosphonic acids, owing to their broad spectrum of biological activities and wide range of applications in the medicinal and agrochemical fields, are very attractive metal-ligand agents that might form biomedical important metal complexes. Thus, a number of aminophosphonate complexes of platinum group metals have been found to possess remarkable antitumor activity while complexes of some other transition and rare-earth metals like technetium, rhenium, samarium and gadolinium have been used either as therapeutic and diagnostic radiopharmaceuticals or as magnetic resonance imaging (MRI) contrast agents. In addition, the high phosphonate affinity towards bone and other calcified tissues may be utilized for the drug targeting based on synthesis of metal complexes linked to bioactive carrier systems, affording better modalities of attack to the site of pathology. In this review article, aminophosphonate metal-based compounds with potential biomedical applications are described. © 2013 Bentham Science Publishers.

Author Keywords

Aminophosphonate metal complexes; Antitumor agents; Enzyme inhibition; Metal complexes; MRI agents; Radiopharmaceuticals

Document Type: Article

Source: Scopus

Duda, B.a b , Tverdomed, S.a , Röschenthaler, G.-V.a

Alkynes XF2C-CBBC-P(O)(OR)2: Synthesis and reactivity

(2013) Journal of Fluorine Chemistry, 152, pp. 29-37.

a School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany

b Freie Universität Berlin, Institute für Chemie and Biochemie, Fabeckstrasse 34-36, 14195 Berlin, Germany

Abstract

Fluoroalkyl alkynylphosphonates are of high stability, and mostly colorless liquid compounds, which are showing constantly growing interest due to their ability to introduce, in one pot, both of these functional groups into one molecule. The fact that they are not commercially available is reflected in the limited number of reactions of such acetylenes. However, the easy and straightforward synthetic methodology to produce the titled compounds for the development of novel compounds with altered chemical, biological and physical properties is making them to go out of the shadow. Therefore, synthesis and reactivity toward cyclization and addition reactions are reviewed herein. © 2013 Elsevier B.V. All rights reserved.

Author Keywords

Cycloaddition reactions; Fluoroalkyl alkynylphosphonates; Synthesis

Document Type: Review

Source: Scopus

Duda, B.a , Tverdomed, S.N.a b , Ionin, B.I.b , Röschenthaler, G.-V.a

Base-promoted heterocyclization of fluorinated alkynylphosphonates with select ortho-aminobenzonitriles

(2012) European Journal of Organic Chemistry, (19), pp. 3684-3690. Cited 4 times.

a School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany

b Department of Organic Chemistry, St. Petersburg Institute of Technology, Technical University, Moskovskii pr 26, 190013 St. Petersburg, Russian Federation

Abstract

The heterocyclization reactions of CF 2-containing alkynylphosphonates with 2-aminobenzonitriles to give 2,3-difunctionalized 4-aminoquinolines were investigated. The influence of the R 1 and R 2 substituents and CF 2X groups on the synthetic efficiency and specificity is also disclosed. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Author Keywords

Cycloaddition; Heterocycles; Regioselectivity; Substituent effects; Synthetic methods

Document Type: Article

Source: Scopus

Kraicheva, I.a , Tsacheva, I.a , Vodenicharova, E.a , Tashev, E.a , Tosheva, T.a , Kril, A.b , Topashka-Ancheva, M.c , Iliev, I.b , Gerasimova, T.c , Troev, K.a

Synthesis, antiproliferative activity and genotoxicity of novel anthracene-containing aminophosphonates and a new anthracene-derived Schiff base

(2012) Bioorganic and Medicinal Chemistry, 20 (1), pp. 117-124. Cited 6 times.

a Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 103A, 1113 Sofia, Bulgaria

b Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113 Sofia, Bulgaria

c Institute of Biodiversity and Ecosystems Research, Bulgarian Academy of Sciences, 2 Gagarin Str., 1113 Sofia, Bulgaria

Abstract

A new Schiff base, 9-anthrylidene-furfurylamine and three novel anthracene-containing α-aminophosphonates, [N-methyl(dimethoxyphosphonyl)- 1-(9-anthryl)]-p-toluidine, [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]-p- toluidine and [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]furfurylamine were synthesized. The compounds have been characterized by elemental analysis, TLC, IR, NMR and fluorescent spectra. The aminophosphonates and their synthetic precursors were tested for in vitro antitumor activity on a panel of seven human epithelial cancer cell lines. Safety testing was performed both in vitro (3T3 NRU test) and in vivo on ICR mice for genotoxicity and antiproliferative activity. 9-Anthrylidene-furfurylamine and [N-methyl(diethoxyphosphonyl)-1-(9- anthryl)]furfurylamine were most potent cytotoxic agents towards colon carcinoma cell line HT-29. The latter compound exhibited also antiproliferative activity to HBL-100, MDA-MB-231 and 647-V cells. The aminophosphonate [N-methyl(dimethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine and its synthetic precursor 9-anthrylidene-p-toluidine were found to be cytotoxic to HBL-100 and HT-29 tumor cell lines, respectively. Moderate genotoxic and antiproliferative activity in vivo and low toxicity to Balb/c 3T3 (clone 31) mouse embryo cells were observed for all tested compounds. The subcellular distribution of two tested compounds in a tumor cell culture system was also studied. © 2011 Elsevier Ltd. All rights reserved.

Author Keywords

Aminophosphonic acids; Antitumor activity; Cytotoxicity; Genotoxicity; NMR; Schiff bases

Document Type: Article

Source: Scopus

Duda, B., Tverdomed, S.N., Röschenthaler, G.-V.

CF 2-Containing acetylenephosphonates in heterocyclization reactions: The first synthesis of 2-difluoromethyl azaxanth-3-ylphosphonates

(2011) Organic and Biomolecular Chemistry, 9 (24), pp. 8228-8232. Cited 2 times.

School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany

Abstract

Acetylenephosphonates carrying the XCF 2 group have been studied in a base-mediated heterocyclization reaction with selected 2-amino-3- formylchromones to give 2-difluoromethyl azaxanth-3-ylphosphonates. The presence of the fluorinated substituent determined the regioselectivity as well as the reactivity of this process. © The Royal Society of Chemistry 2011.

Document Type: Article

Source: Scopus

Mucha, A., Kafarski, P., Berlicki, Ł.

Remarkable potential of the α-aminophosphonate/phosphinate structural motif in medicinal chemistry

(2011) Journal of Medicinal Chemistry, 54 (17), pp. 5955-5980. Cited 54 times.

Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeze Wyspiańskiego 27, 50-370 Wrocław, Poland

Document Type: Review

Source: Scopus

Tverdomed, S.N.a b , Kolanowski, J.a , Lork, E.c , Röschenthaler, G.-V.a

An effective synthetic route to ortho-difluoromethyl arylphosphosphonates: Studies on the reactivity of phosphorus- and fluorine-containing functions

(2011) Tetrahedron, 67 (21), pp. 3887-3903. Cited 4 times.

a School of Engineering and Science, Jacobs University Bremen GGmbH, Campus Ring 1, 28759 Bremen, Germany

b Department of Organic Chemistry, St. Petersburg State Institute of Technology, Technical University, Moskovskii pr. 26, St. Petersburg 190013, Russian Federation

c Institute of Inorganic and Physical Chemistry, University of Bremen, Leobener Strasse, 28359 Bremen, Germany

Abstract

Herein, we report a new and convenient methodology for the synthesis of ortho-XCF2 arylphosphonates via Diels-Alder reaction of selected 1,3-butadienes with XCF2-≡-P(O)(OEt)2, followed by the aromatization of the cyclic vinylphosphonates obtained using the KMnO 4/Al2O3 system. The reactivity of ortho-XCF2 arylphosphonates was then examined to give the respective dichlorides that were converted to the corresponding phosphonic acids, phosphine oxides or a carboxylic acid (upon hydrolysis of the CF2Br group). When ortho-XCF2 arylphosphonates (X=Br) were treated with Zn/CuBr and an electrophile, the dimeric product ArCFCFAr was isolated only. The lithiation of the CF2H group (X=H) allowed however to obtain products of nucleophilic substitution with various electrophiles. © 2011 Elsevier Ltd. All rights reserved.

Author Keywords

Alkynes; Aromatization; Arylphosphonates; Cyclization; Regioselectivity

Document Type: Article

Source: Scopus

Jansa, P., Holý, A., Dračinský, M., Baszczyňski, O., Česnek, M., Janeba, Z.

Efficient and 'green' microwave-assisted synthesis of haloalkylphosphonates via the Michaelis-Arbuzov reaction

(2011) Green Chemistry, 13 (4), pp. 882-888. Cited 15 times.

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, Prague, CZ-166 10, Czech Republic

Abstract

This paper deals with a novel, efficient and environmentally friendly synthesis of dialkyl haloalkylphosphonates via a microwave-assisted Michaelis-Arbuzov reaction. The approach is solventless, requires only one equivalent of each of the starting compounds, and provides high yields of pure products from which the impurities are easy to remove. The process has been optimised for batch and flow reactors and is especially profitable for the production of key intermediates in synthesis of Ethephon or acyclic nucleoside phosphonates such as adefovir, tenofovir, and cidofovir. © The Royal Society of Chemistry.

Document Type: Article

Source: Scopus

Duda, B.a , Tverdomed, S.N.a b , Röschenthaler, G.-V.a

Synthesis of 2-perfluoroalkyl 4 H - And 2 H-chromenylphosphonates mediated by amines and phosphines

(2011) Journal of Organic Chemistry, 76 (1), pp. 71-79. Cited 7 times.

a School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany

b Department of Organic Chemistry, St. Petersburg State Institute of Technology, Technical University, Moskovskii pr. 26, St. Petersburg 190013, Russian Federation

Abstract

An efficient synthesis of 2-perfluoroalkyl 4H-chromen-3-ylphosphonates 4a-i (RF = CF3) and 5a-i (RF = C2F 5) has been accomplished via regioselective cycloaddition of 2-hydroxybenzaldehydes to diethyl 3,3,3-trifluoropropyn-1-yl- and diethyl 3,3,4,4,4-pentafluorobutyn-1-ylphosphonate, using trialkyl amines or phosphines as mediators. 2H-Chromen-3-ylphosphonates 6a-i were regioselectively obtained in the presence of triphenylphosphine. A convenient method for the isomerization of 4H-chromen-3-ylphosphonates into 2H-chromen-3-ylphosphonates 6a-i (R F = CF3) and 7a-i (RF = C2F 5) was established. © 2010 American Chemical Society.

Document Type: Article

Source: Scopus

Ho, C.-Y.a , Chan, C.-W.a , Wo, S.-K.b , Zuo, Z.b , Chan, L.-Y.a

Nitrile assisted, Brønsted acid catalyzed regio and stereoselective diarylphosphonylation of allyl silyl ethers

(2010) Organic and Biomolecular Chemistry, 8 (15), pp. 3480-3487. Cited 2 times.

a Center of Novel Functional Molecules, Chinese University of Hong Kong, Shatin New Territories, Hong Kong

b School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Shatin New Territories, Hong Kong

Abstract

We have discovered a mild, catalytic protocol for the regio- and stereoselective synthesis of trisubstituted allyl diarylphosphonates from the corresponding disubstituted allyl silyl ethers, circumventing the challenges related to the preparation and availability of stereodefined trisubstituted olefins. A closely related arylation reaction was also discovered during the methodology development. By simply switching the reaction medium, high phosphonylation/arylation ratios and vice versa can be achieved. This may not be a direct result of changing solvent polarity. The allyl diarylphosphonates were evaluated as carboxylesterase inhibitors, and the screening results revealed that the inhibitory efficiency is highly related to the choice of alkenes and aryl substituents. © The Royal Society of Chemistry 2010.

Document Type: Article

Source: Scopus

Peng, A.-Y.a , Guo, Y.-J.a , Ke, Z.-H.a , Zhu, S.b

Alcoholysis of phosphaisocoumarins and synthesis of 2-(2-oxoalkyl) phenylphosphonates

(2008) European Journal of Organic Chemistry, (31), pp. 5277-5282. Cited 2 times.

a School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xingangxi Lu, Guangzhou 510275, China

b Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China

Abstract

Phosphaisocoumarins do not undergo aminolysis, but instead they were found to be susceptible to alcoholysis in the presence of alcohols and primary amines. This paper examined this unexpected alcoholysis reaction and found that in the presence of Et 3N or K 2CO 3, 4-unsubstituted- and 4-chlorophosphaisocoumarins underwent the alcoholysis reaction smoothly to give a series of 2-(2-oxoalkyl)phenylphosphonates in good yields, whereas 4-iodo- and 4-bromophosphaisocoumarins underwent a dehalogenation-alcoholysis tandem reaction. The possible mechanism for the alcoholysis reaction was discussed. In addition, direct access to 2-(2-oxoalkyl)-phenylphosphonates was developed by the mercury(II)-catalyzed hydration of 2-(1-alkynly)phenylphosphonates with high regioselectivity. In a preliminary study, the obtained novel keto phosphonates showed medium inhibitory activity towards α-chymotrypsin. © Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Author Keywords

Alcoholysis; Alkynes; Hydration; Phosphonates; Phosphorus heterocycles

Document Type: Article

Source: Scopus