Functional bisphosphonate synthesis for the development of new anti-resorption bone drug candidates

Bortolamiol, Enrica; Chiminazzo, Andrea; Sperni, Laura; Borsato, Giuseppe; Fabris, Fabrizio; Scarso, Alessandro

doi:10.1039/c9nj02504a

Cited by 5 publications

(2 citation statements)

References 53 publications

(38 reference statements)

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“…Phosphonate-containing organic molecules such as aminophosphonate and bisphosphonate derivatives are well-known for their biological activities [1][2][3][4][5]. Consequently, many routes have been reported for their synthesis [6][7][8][9][10]. In particular, bisphosphonates have shown high potential as enzyme inhibitors [11][12][13], anti-inflammatory agents [14] or cancer treatments [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Diethyl(benzamido(diisopropoxyphosphoryl)methyl) phosphonate

López-Francés

Palácios

Maestro

et al. 2022

Molbank

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Bisphosphonates are widely used in medicine and related areas, mainly for the treatment of bone diseases, such as osteoporosis. However, their synthesis is usually performed under harsh reaction conditions. In order to overcome this limitation, the present work illustrates a new synthetic route to access the title α-aminobisphosphonate in milder reaction conditions using α-phosphorylated imines as key intermediates.

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Section: Introductionmentioning

confidence: 99%

Diethyl(benzamido(diisopropoxyphosphoryl)methyl) phosphonate

López-Francés

Palácios

Maestro

et al. 2022

Molbank

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“…[27] We considered in particular the modification of vinylidenebisphosphonate ester 3 as an important scaffold obtained by reaction of diethyl phosphite with methylene chloride via formation of methylenebisphosphonate ester 2 (Scheme 2 ). 3 is a versatile electrophile that through Michael [28] or hetero‐Michael [29] addition reactions enable the preparation of a wide range [30] of potential drug candidates to contrast osteoporosis and bone diseases.…”

Section: Introductionmentioning

confidence: 99%

Modification of Amorphous Mesoporous Zirconia Nanoparticles with Bisphosphonic Acids: A Straightforward Approach for Tailoring the Surface Properties of the Nanoparticles

Scarso

Hossain

Florean

et al. 2021

Chemistry A European J

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The use of readily prepared bisphosphonic acids obtained in few steps through a thio‐Michael addition of commercially available thiols on tetraethyl vinylidenebisphosphonate enables the straightforward surface modification of amorphous mesoporous zirconia nanoparticles. Simple stirring of the zirconia nanoparticles in a buffered aqueous solution of the proper bisphosphonic acid leads to the surface functionalization of the nanoparticles with different kinds of functional groups, charge and hydrophobic properties. Formation of both chemisorbed and physisorbed layers of the bisphosphonic acid take place, observing after extensive washing a grafting density of 1.1 molecules/nm2 with negligible release in neutral or acidic pH conditions, demonstrating stronger loading compared to monophosphonate derivatives. The modified nanoparticles were characterized by IR, XPS, ζ‐potential analysis to investigate the loading of the bisphosphonic acid, FE‐SEM to investigate the size and morphologies of the nanoparticles and 31P and 1H MAS NMR to investigate the coordination motif of the phosphonate units on the surface. All these analytical techniques demonstrated the strong affinity of the bisphosphonic moiety for the Zr(IV) metal centers. The functionalization with bisphosphonic acids represents a straightforward covalent approach for tailoring the superficial properties of zirconia nanoparticles, much straightforward compared the classic use of trisalkoxysilane or trichlorosilane reagents typically employed for the functionalization of silica and metal oxide nanoparticles. Extension of the use of bisphosphonates to other metal oxide nanoparticles is advisable.

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