95601-03-9

Upstream product

• 762-04-9 phosphonic acid diethyl ester 
• 243137-81-7 1,1,2,2,3,3,4,4,4-Nonafluoro-butane-1-sulfonic acid (E)-1-(diethoxy-phosphoryl)-2-phenyl-vinyl ester 
• 3450-67-7 diethyl phenylethynylphosphonate 
• 536-74-3 phenylacetylene 
• 1660-94-2 Tetraethyl methylenediphosphonate 
• 705-60-2 (2-nitroprop-1-enyl)benzene 
• 100-52-7 benzaldehyde 

Downstream Products

• 78-40-0 triethyl phosphate 
• 20408-33-7 diethyl (E)-(2-phenylethenyl)phosphonate 
• 1436429-26-3 tetraethyl 1,2-epoxy-2-phenylethyl bisphosphonate 
• 105532-75-0 2-(phenyl)-ethene-1,1-bisphosphonic acid 
• 1316645-29-0 C₂₆H₃₇NO₈P₂ 
• 1316645-91-6 (2R,3S)-methyl 2-amino-4,4-bis(diethoxyphosphoryl)-3-phenylbutanoate 
• 1316645-42-7 (2S,3R)-methyl 2-benzamido-4,4-bis(diethoxyphosphoryl)-4-hydroxy-3-phenylbutanoate 

Relevant academic research and scientific papers

Challenging synthesis of bisphosphonate derivatives with reduced steric hindrance

An alternative approach is reported for the synthesis of methyl ester protected bisphosphonate building blocks, such as methylene bisphosphonate, vinylidenebisphosphonate and aryl substituted prochiral vinylidenebisphosphonates, that cannot be obtained directly from dimethyl phosphite and dichloromethane.

Synthesis and biological evaluation of 2-substituted vinylgembisphosphonates against Plasmodium falciparum and Trypanosoma brucei

A series of 2-substituted vinylidene-1,1-bisphosphonate esters and their acids were synthesized and tested in?vitro for activity against Plasmodium falciparum and Trypanosoma brucei. For each compound, % parasite viability in treated wells was calculated relative to untreated controls for both P. falciparum and T. brucei. Fifty percentage inhibitory concentration (IC50) was also determined for the compounds. Chloroquine and pentamidine were used as positive control drug standards for activity against P. falciparum and T. brucei, respectively. The esters had better antiparasitic activity compared to their corresponding acids. Some of the compounds reduced % parasite viability to as low as 24.3% for P. falciparum and down to 0.602% for T. brucei. Tetraethyl-2-(o-tolyl)-ethene-1,1-bisphosphonate (3b) recorded the best IC50 against T. brucei which was 0.0345 μmol/mL.

Design, synthesis and P-gp induction activity of aryl phosphonate esters: Identification of tetraethyl-2-phenylethene-1,1-diyldiphosphonate as an orally bioavailable P-gp inducer

The clearance of amyloid-beta is mediated by the P-glycoprotein (P-gp) transporter pump located at the blood brain barrier. Therefore, the induction of P-gp has been considered as a potential therapeutic strategy for the treatment of Alzheimer's disease. The expression of P-gp is regulated through a nuclear receptor, pregnane X receptor (PXR). Thus, herein we investigated the potential of a known PXR activator, diphosphonate ester SR12813 (6a), for P-gp induction activity and further studied its structure-activity relationship. The diphosphonate ester SR12813 along with three series of analogs, viz. aryl alkylidene, aryl alkynyl, and aryl α-amino phosphonate esters, were synthesized and screened for P-gp induction activity in P-gp overexpressing adenocarcinoma LS180 cells using rhodamine 123 efflux assay. The parent compound SR12813 along with several new analogs displayed P-gp induction activity at 5 μM. Western blot analysis indicated that tetraethyl-2-phenylethene-1,1-diyldiphosphonate (6c) and tetraethyl-2-(anthracene-10-yl)ethene-1,1-diyldiphosphonate (6s) showed 7-8-fold increase in P-gp expression in LS180 cells. The diphosphonate ester 6c displayed excellent aqueous solubility, no cytochrome P450 inhibition liability and no efflux pump substrate liability. Furthermore, it exhibits an excellent oral pharmacokinetic profile in BALB/c mice with AUC0-∞ of 2067 ng h mL-1 and 37.6% oral bioavailability. The results presented here clearly indicate the potential of this scaffold to increase the clearance of brain Aβ across the BBB and thus its promise for development as a potential anti-Alzheimer agent.

Dioxirane oxidation of 2-Aryl-1-vinyl-1, 1-diphosphane dioxide: A convenient approach for the synthesis of novel 1,2-epoxy-2-aryl ethylgembisphosphonates

The synthesis of tetraethyl 1,2-epoxy-2-aryl ethylgembisphosphonates by direct epoxidation of 2-aryl,vinyl-1,1-diphosphonate derivatives with ethyl methyldioxirane generated in situ from potassium hydrogen monopersulfate (caroate) and butanone in a phase

A Facile Cu(I)/TF-BiphamPhos-catalyzed asymmetric approach to unnatural α-amino acid derivatives containing gem-bisphosphonates

A novel catalytic asymmetric Michael addition of azomethine ylide with β-substituted alkylidene bisphosphates was realized in the presence of a chiral copper(I)/TF-BiphamPhos complex. The present system provides a unique and facile access to enantioenriched unnatural α-amino acid derivatives containing gem-bisphosphonates (gem-BPs) in high yields with excellent diastereoselectivities and enantioselectivities. Subsequent transformations lead to the expedient preparation of biologically active unnatural α-amino acid derivatives containing BPs and bisphosphonic acids without loss of diastereo- and enantiomeric excess.

Phosphine-catalyzed α-P-addition on activated alkynes: A new route to P-C-P backbones

(Chemical Equation Presented) n-Tributylphosphine was found to efficiently catalyze the α-P addition of H-phosphonates, H-phosphinates, and H-phosphine oxide pronucleophiles on alkynes bearing phosphane oxide activating moieties. The reaction leads to 2-a

New synthesis of gem-bis(phosphono)ethylenes and their applications

Palladium-catalyzed cross-coupling reaction of α-phosphonovinyl nonafluorobutanesulfonates (nonaflates) 1 with dialkyl phosphites gave versatile intermediate reagents, gembis(phosphono)ethylenes 2a-d in 35-93% yields. The reaction of bis(diethylphosphono)

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS 62. REACTIONS OF METHYLENEBISPHOSPHONATE WITH α-NITROALKENES. A NOVEL SYNTHESIS OF ETHENYLIDENEBISPHOSPHONATES AND 2-ISOXAZOLINE-5,5-DIYLBISPHOSPHONATES

Reaction of methylenebisphosphonate with α-nitroalkenes followed by addition of trimethylchlorosilane leads to the formation of ethenylidenebisphosphonates and trimethylsilyl nitronate in almost quantitative yield.These two products, upon prolonged reaction at ambient temperature, provide 2-isoxazoline-5,5-diylbisphosphonates via regioselective 1,3-dipolar cycloaddition in high yield.Key words: Methylenebisphosphonate; α-nitroalkenes; ethenylidenebisphosphonate; 2-isoxazoline-5,5-diylbisphosphonate; 1,3-dipolar cycloaddition.