Bisphosphonic acids

Chemical Name (1-Hydroxyethylidene)bisphosphonic acid disodium salt Common Name —... 

CN [ 1 -hydroxy-3-(methylpentylaniino)propylidene]bisphosphonic acid monosodium salt monohydrate anhydrous... 

G)H2Cl7N20 86567-35-0) see Apraclonidine (dichloromethylene)bisphosphonic acid tetrakis(l-methyl-ethyl) ester... 

Bisphosphonic acids and their salts are analogs of pyrophosphate where the P-O-P linkage of the latter has been replaced by P-C-P. Bisphosphonates are known to inhibit bone resorption, and have attracted much attention as potential therapeutic agents. Bisphosphonates do not absorb or fluoresce, and sample matrix interferences can make detection difficult, especially in biological samples. Successful applications of IEC to bisphosphonate analysis have been described.173174... 

Hertzog, K., Naumann, P., and Schuelke, U., Combined Production of Substituted w-Alkyl l-a,a-Bisphosphonic Acids and Alkyl Phosphites, East German Patent 222,599, 1985. 

Enantioselective hydrogenation of prochiral ketones has rarely been studied in aqueous biphasic media. In addition to the chiral bisphosphonic acid derivatives of 1,2-cyclohexanediamine [130], the protonated 4,4 -, 5,5 -, and 6,6 -amino-methyl-substituted BINAP (diamBINAP 2HBr) ligands (Scheme 38.7) served as constituents of the Ru(II)-based catalysts in the biphasic hydrogenations of ethyl acetoacetate [131, 132]. These catalysts were recovered in the aqueous phase and used in at least four cycles, with only a marginal loss of activity and enantio-selectivity. 

Cohen H, Alferiev IS, Monkkonen J, et al. Synthesis and preclinical pharmacology of 2-(2-aminopjTimidinio) ethylidene-l,l-bisphosphonic acid betaine (ISA-13-l)-a novel bisphosphonate. Pharm Res 1999 16 1399-1406. 

Fig. 14 Schematic representation of the creation of a bilayer by alternatively reacting the surface with a bisphosphonic acid and a metal salt...

C4HiCI7N20 86861-35-0) sec Apraclonidine (dichloromethylcne)bisphosphonic acid tclrakisfl-methyl-cthyl) ester... 

The first authentic synthesis of a bisphosphonic acid, l-hydroxyethane-l,l-bisphos-phonic acid (etidronic acid), was published by von Baeyer and Hofmann in 1897 [1], although it is possible that the same compound had already been obtained in 1865 by Menschutkin [2], The synthetic approach to BPs employed today differs only little from that used over a hundred years ago, and it is still based on the reaction of a carboxylic acid with phosphorus trichloride with the addition of some water [3], (Note BPs are usually represented as the free bisphosphonic acids the generic names given refer, however, to their salt forms.)... 

Ever since the discovery of the steam engine, the precipitation of insoluble calcium salts in boilers and pipes has been causing severe problems. Thus, the discovery that low concentrations of phosphoric, pyrophosphoric or bisphosphonic acids can prevent scale had enormous industrial importance. This information, combined with the characteristic ability of BPs to chelate virtually every heavy metal, laid the basis for their wide industrial importance [4], As a result, bisphosphonates are in current use in a wide variety of industrial areas, as scale inhibitors, for the treatment of metal and other surfaces, in water treatment, in the textile industry, in the detergent and cosmetic industry, in the polymer industry, and several others [4],... 

Dauer, R. R. DiMichele, L. Futran, M. Kieczykowski, G. R., Process for Producing N-amino-l-hydroxy-alkylidene-l,l-bisphosphonic acids. U.S. 5,510,517,1994 (to Merck). 

Kieczykowski, G.R Process for Preparing 4-Amino-1 -Hydroxy butylidene-1,1 -Bisphosphonic Acid (ABP) or Salts Thereof. U.S. Patent 5,019,651, May 28, 1991. 

Hutchinson, D.W., and Thornton, D.M., A simple synthesis of monofluoromethylene bisphosphonic acid, J. Organomet. Chem., 340, 93, 1988. 

Griffiths, D.V., Hughes, J.M., Brown, J.W., Caesar, J.C., Swctnam, S.P., Cumming, S.A., and Kelly, J.D., The synthesis of l-amino-2-hydroxy- and 2-amino-l-hydroxyethylene-l,l-bisphosphonic acids and their /V-inelliylaled derivatives. Tetrahedron, 53, 17815, 1997. 

Turhanen, P.A., Ahlgren, M.J., Jarvinen, T., and Vepsalainen, J.J., Bisphosphonate prodrugs. Synthesis and identification of (1-hydroxyethylidene)-1,1-bisphosphonic acid tetraesters by mass spectrometry, NMR spectroscopy and X-ray crystallography. Phosphorus, Sulfur Silicon Relat. Elem., 170, 115, 2001. Pudovik, A.N., Batyeva, E.S., and Zamaletdinova, G.U., Reaction of a trimethylsilyl phosphite with O,O-diethyl acetyIphosphonate, Zh. Obshch. Khim., 43, 680, 1973 J. Gen. Chem. USSR (Engl. Transl.), 43, 676, 1973. 

In continuation of studies on the formation and reactions of 1-hydroxyalkyl-l,1-bisphosphonic acid cyclic esters (Organophosphoms Chemistry, 1988, j, 161), the a,u-dioxoalkanediphosphonic tetraesters (167 n=3-8) have been shown to react with more hydrogen phosphonate to give the a, (u-dihydroxy-a, o, u), co-bis [ bis phosphonic acid)] esters (168) cross-reactions e.g., between (167b) and dimethyl phosphonate (affording the same product as that obtained from (167a)... 

EINECS 227-833-4 Ethanolaminedi(methylenephos-phonic acid) (((2-Hydroxyethyl)imino)bis(methylene))-bisphosphonic acid 2-Hydroxyethylbis(phosphono-methyl)amine 2-... 

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