34162-79-3

Upstream product

• 37465-31-9 1,1-bis(diethylphosphono)ethylene 
• 2666-14-0 ethane-1-hydroxy-1,1-diphosphonic acid tetrasodium salt 

Downstream Products

• 960593-08-2 C₁₄H₂₄O₆P₂S 
• 960593-10-6 C₁₂H₂₀O₆P₂S 
• 960593-09-3 C₁₃H₂₂O₆P₂S 
• 67293-68-9 tetramethyl ethenylidene-1,1-bis(phosphonate) 
• 87774-70-7 (2-Benzylsulfanyl-1-phosphono-ethyl)-phosphonic acid 
• 87774-69-4 (1-Phosphono-2-p-tolylsulfanyl-ethyl)-phosphonic acid 

Relevant academic research and scientific papers

Synthesis of Ethenylidenebis(phosphonic acid) and Its Tetraalkyl Esters

A new method for the preparation of tetraalkyl ethenylidenebis(phosphonates) has been developed.This two-step procedure involves the base-catalyzed reaction of a methylenebis(phosphonate) ester with paraformaldehyde followed by acid-catalyzed elimination of methanol.The effects of variations in the reaction conditions of the first step of this process are described.Ethenylidenebis(phosphonate) esters can be converted to the free acid by reaction with bromotrimethylsilane.

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.

Isoprenoid Biosynthesis Inhibitors Targeting Bacterial Cell Growth

We synthesized potential inhibitors of farnesyl diphosphate synthase (FPPS), undecaprenyl diphosphate synthase (UPPS), or undecaprenyl diphosphate phosphatase (UPPP), and tested them in bacterial cell growth and enzyme inhibition assays. The most active compounds were found to be bisphosphonates with electron-withdrawing aryl-alkyl side chains which inhibited the growth of Gram-negative bacteria (Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa) at ～1–4 μg mL?1levels. They were found to be potent inhibitors of FPPS; cell growth was partially “rescued” by the addition of farnesol or overexpression of FPPS, and there was synergistic activity with known isoprenoid biosynthesis pathway inhibitors. Lipophilic hydroxyalkyl phosphonic acids inhibited UPPS and UPPP at micromolar levels; they were active (～2–6 μg mL?1) against Gram-positive but not Gram-negative organisms, and again exhibited synergistic activity with cell wall biosynthesis inhibitors, but only indifferent effects with other inhibitors. The results are of interest because they describe novel inhibitors of FPPS, UPPS, and UPPP with cell growth inhibitory activities as low as ～1–2 μg mL?1.

Bisphosphonate-Prodrugs

The present invention relates to a prodrug, comprising a pharmaceutically and/or diagnostically active compound, and one or more bisphosphonate groups, to a process for producing such a prodrug, and to a pharmaceutical composition comprising said prodrug, to be used for the treatment of bone-related disorders such as bone cancer.

Development of novel bisphosphonate prodrugs of doxorubicin for targeting bone metastases that are cleaved pH dependently or by cathepsin B: Synthesis, cleavage properties, and binding properties to hydroxyapatite as well as bone matrix

Bone metastases are a frequent cause of morbidity in cancer patients. The present palliative therapeutic options are chemotherapy, hormone therapy, and the administration of bisphosphonates. The affinity between bisphosphonates and the apatite structure of bone metastases is strong. Thus, we designed two low-molecular-weight and water-soluble prodrugs which incorporate a bisphosphonate group as a bone targeting ligand, doxorubicin as the anticancer agent, and either an acid-sensitive bond (1) or a cathepsin B cleavable bond (3) for ensuring an effective release of doxorubicin at the site of action. Cleavage studies of both prodrugs showed a fast release of doxorubicin but sufficient stability over several hours in human plasma. Effective binding of prodrug 1 and 3 was demonstrated with hydroxyapatite and with native bone. In orientating toxicity studies in nude mice, the MTD of 1 was 3-fold higher compared to conventional doxorubicin, whereas 3 showed essentially the same MTD as doxorubicin.

ETUDE PAR RMN DES REACTIONS D'ADDITION DES SPIROPHOSPHORANES A LIAISON P-H SUR LE TETRA ETHYLE ET LE TETRA METHYLE ETHYLIDENE BIS PHOSPHONATE

The spirophosphoranes 1 to 4,6 and 7 bearing a P-H bond have been condensed with tetraethyl (z) or tetra methyl (x) ethenylidene bis phosphonate by a Michael type addition reaction.The resulting compounds: Spirophosphoranes-bis phosphonates 1x, 3x, 4x, 5x, 6x, 7x and 2z, 4z, 5z, 7z havd been studied by NMR 1H, 31P and 13C.With the spirophosphorane 7 that contain 90percent of its tricoordinated form 7' the formation of an intermediate 7ax or 7az has been observed: 7ax or 7az give rise to a slow transposition at 20 deg C or a fast rearrangement at 60 deg C into phosphorane 7x or 7z.Key words: Ethenylidene bis phosphonate, spirophosphorane, phosphorane-bis phosphonate, stereomutation, tautomeric equilibrium PIII-PV, diastereotopy.

Process for the preparation of vinyldiphosphonic acid and salts thereof

An improved process for the preparation of vinyldiphosphonic acid is disclosed. The process involves elimination of a volatile acid from a 1-(O-acyl)-ethane-1,1-diphosphonic acid. The starting materials may be prepared by reacting 1-hydroxyethane-1,1-diphosphonic acid with the corresponding acid or directly by reacting the acid with phosphorous acid and an acyl anhydride.