32545-75-8

Usage

Uses

Used in Pharmaceutical Industry:
(Morpholin-4-ylmethylene)bisphosphonic acid is used as a therapeutic agent for the treatment of osteoporosis and other bone-related diseases. Its application is based on its ability to disrupt the activity of osteoclasts, the cells responsible for bone tissue breakdown, thereby increasing bone density and reducing the risk of fractures.
Used in Oncology Research:
(Morpholin-4-ylmethylene)bisphosphonic acid is used as a potential anticancer agent in the treatment of certain types of tumors. Its application in this field is due to its discovered anticancer properties, which are currently under investigation for their effectiveness and mechanisms of action in cancer treatment.

InChI:InChI=1/C5H13NO7P2/c7-14(8,9)5(15(10,11)12)6-1-3-13-4-2-6/h5H,1-4H2,(H2,7,8,9)(H2,10,11,12)

Upstream product

• 59646-46-7 tetraethyl (morpholinomethylene)bisphosphonate 
• 1404287-59-7 tetra(trimethylsilyl)?morpholin-4-ylmethylenediphosphonate 
• 4394-85-8 4-morpholinecarboxaldehyde 
• 110-91-8 morpholine 

Relevant academic research and scientific papers

Tris(trimethylsilyl) phosphite as key synthon for convenient synthesis of new organosilicon(phosphorus)-containing N-heterocycles

The new functionalized hydroxymethylphosphonic and methylenediphosphonic acids are synthesized via unique reaction of tris(trimethylsilyl) phosphite and N-formyl N-heterocycles, N-substituted 4-piperidones, 3-quinuclidone, and 2-adamantanone at the presence of effective catalyst – trimethylsilyl triflate under mild conditions.

Interactions of N-heteroalkylaminomethylenebisphosphonic acids with Cd(II) ions: Electrochemical and spectroscopic investigations

Abstract The aminomethylenebisphosphonates are known to be excellent chelators for many metal ions. In this work, the coordination properties of three different aminomethylenebisphosphonates with N-substituted heteroalkyl moieties (L1, L2 and L3) and their N-pyridyl derivative (L4) toward cadmium(II) ions are described. Due to their coordination abilities over a broad range of pH, the compounds of this group are good candidates for heavy metal detoxification. To determine the stability constants and the coordination mode of formed aminomethylenebisphosphonate-cadmium(II) complexes, four analytical methods were employed: potentiometry, pulse polarography (DPP), nuclear magnetic resonance spectroscopy (NMR) and electrospray ionization mass spectrometry (ESI-MS). The studies performed revealed that ligands L1, L2 and L3 possessed similar coordination properties, with Cd(II) ions binding below pH 2 to form equimolar complexes and above pH 6 to form bis-complexes. The ligand L4 behaved in a different way, forming six complexes of varied stoichiometry: CdH4L3, CdH3L3, CdHL2, CdL2, CdH2L and Cd3H4L3. The hypothetical competition plot between common complexone d-penicillamine and the studied ligands showed better complexation properties for the aminomethylenebisphosphonates in the pH range 2-6 than for neutral pH, where above neutral pH d-penicillamine bound Cd(II) ions significantly better.

Synthesis of new types of aminomethylenediphosphorus-containing acids and their derivatives

Convenient methods for synthesis of various aminomethylenediphosphorus-containing acids and their derivatives starting from available trimethylsilyl esters of hypophosphorous and phosphorous acids, ethoxymethyleneimine hydrochlorides, and N-substituted formamides have been proposed. Selected properties of the obtained compounds have been examined.

Synthesis and reactivity of the new trimethylsilyl esters of aminomethylenebisorganophosphorus acids

The interaction of trimethylsilyl esters of trivalent organophosphorus acids containing PH and POSiMe3 fragments in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst is proposed as a convenient method for the synthesis of new trimethylsilyl esters of aminomethylenebisorganophosphorus acids with three and four coordinated phosphorus. Also the new functionalized derivatives of the aminomethylenebisphosphinic acids with substituted hydroxymethyl moieties are synthesized, and some properties of the obtained compounds are presented.

Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC50 50 ～ 4-9 μM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC50 ～ 10-20 μM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pKa values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC50 values 50 values around 1 μM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.

1-Aminoalkane-1,1-diphosphonic acids and their salts

A process for the production of 1-aminoalkane-1,1-diphosphonates of the formula SPC1 Wherein R1 is a member selected from the group consisting of hydrogen, lower alkyl and phenyl, R2 and R 3 are members selected from the group consisting of hydrogen, alkyl having 1 to 22 carbon atoms, cycloalkyl having 5 to 6 carbon atoms, phenyl, alkylphenyl having 7 to 18 carbon atoms, phenylalkyl having 7 to 18 carbon atoms and together with the nitrogen atom, piperidino, pyrrolidino and morpholino, and X is a member selected from the group consisting of hydrogen, alkali metal, ammonium, pyridinium, guanidinium and mono-, di-, and tri-lower-alkanol-ammonium with the proviso that at least one of R1, R2 and R3 is other than hydrogen, which consists essentially in reacting a phosphorus trihalide selected from the group consisting of phosphosus trichloride and phosphorus tribromide with a monocarboxylic acid amide of the formula SPC2wherein the molecular weight of said carboxylic acid amide is over 46 and R1, R2 and R 3 have the above assigned meanings, at a temperature of from 0° to 75°C, subjecting the resultant reaction product to hydrolysis, and recovering said 1-aminoalkane-1,1-diphosphonates. The 1-aminoalkane-1,1-diphosphonates, some of which are novel, are capable of forming complexes with heavy metals.