78715-57-8

Usage

Uses

Used in Pharmaceutical Industry:
Tetraisopropyl Fluoromethylenediphosphonate is used as a chemical intermediate for the synthesis of 5'-diphosphate and 5'-triphosphate mimics, which are crucial in the development of transcriptase inhibitors. These inhibitors play a significant role in the pharmaceutical industry for the treatment of various diseases by targeting and inhibiting the activity of specific enzymes involved in the transcription process.

InChI:InChI=1/C13H29FO6P2/c1-9(2)17-21(15,18-10(3)4)13(14)22(16,19-11(5)6)20-12(7)8/h9-13H,1-8H3

Upstream product

• 1660-95-3 Tetraisopropyl methylenediphosphonate 

Downstream Products

• 84675-08-1 (E,E)-di-isopropyl 1-fluoro-4-phenylbuta-1,3-dienylphosphonate 
• 84675-08-1 (E,Z)-di-isopropyl 1-fluoro-4-phenylbuta-1,3-dienylphosphonate 
• 10595-93-4 1-(fluoromethylene)-1,1-bisphosphonic acid 
• 84675-35-4 di-isopropyl 2-phenylpropylphosphonate 
• 84675-35-4 di-isopropyl 2-phenylpropylphosphonate 
• 109756-31-2 di-isopropyl 1-fluoro-4-phenylbutylphosphonate 
• 84675-17-2 (E)-1-fluoro-2-phenylprop-1-enylphosphonate 
• 84675-17-2 (Z)-1-fluoro-2-phenylprop-1-enylphosphonate 
• 84675-35-4 di-isopropyl 1-fluoro-2-phenylpropylphosphonate 
• 85093-31-8 di-isopropyl 2-phenylpropylphosphonate 

Relevant academic research and scientific papers

Synthesis and Immunomodulatory Activity of Fluorine-Containing Bisphosphonates

Immune checkpoint blockade using anti-PD-1/PD-L1 or anti-CTLA-4 monoclonal antibodies (mAbs) has revolutionized cancer treatment. However, many types of cancer do not respond and for those that do, only a minority of patients achieve durable remissions. Therefore, oncoimmunologists are working to develop adoptive cell therapies for non-hematopoietic tumors by harnessing immune effector cells such as αβ T cells and γδ T cells. In contrast to conventional αβ T cells that recognize peptides in the context of MHC class I or II molecules, γδ T cells expressing Vγ2Vδ2 T cell receptors (also termed Vγ9Vδ2) are stimulated by isoprenoid metabolites (phosphoantigens) such as isopentenyl diphosphate in a butyrophilin-3A1-dependent manner. Vγ2Vδ2 T cells kill almost all types of tumor cells that have been treated with bisphosphonates. In this study, we synthesized a series of fluorine-containing bisphosphonates based on current drugs and found that they stimulated Vγ2Vδ2 T cell killing of tumor cells. A fluorine-containing prodrug analogue of zoledronate where phosphonate moieties were masked with pivaloyloxymethyl groups markedly enhanced Vγ2Vδ2 T-cell-mediated cytotoxicity, and also promoted the expansion of peripheral blood Vγ2Vδ2 T cells. These results demonstrate that a prodrug of a fluorine-containing zoledronate analogue can sensitize tumor cells for killing as well as expand Vγ2Vδ2 T cells for adoptive cell therapy.

Difluoromethylenediphosphonate: A convenient, scalable, and high-yielding synthesis

Since the firsf disclosure of difluoromethylenediphosphonate, 2, almost 40 years ago, interest in this compound has flourished in several research areas. In this paper, we present a convenient, high-yielding (99% overall) method for the preparation of milligram to multigram quantities of 2 (as the bis(tributylammonium salt, 2b) in a solid form that is easy to handle.

Bisphosphonate-Generated ATP-Analogs Inhibit Cell Signaling Pathways

Bisphosphonates are a major class of drugs used to treat osteoporosis, Paget's disease, and cancer. They have been proposed to act by inhibiting one or more targets including protein prenylation, the epidermal growth factor receptor, or the adenine nucleotide translocase. Inhibition of the latter is due to formation in cells of analogs of ATP: the isopentenyl ester of ATP (ApppI) or an AppXp-type analog of ATP, such as AMP-clodronate (AppCCl2p). We screened both ApppI as well as AppCCl2p against a panel of 369 kinases finding potent inhibition of some tyrosine kinases by AppCCl2p, attributable to formation of a strong hydrogen bond between tyrosine and the terminal phosphonate. We then synthesized bisphosphonate preprodrugs that are converted in cells to other ATP-analogs, finding low nM kinase inhibitors that inhibited cell signaling pathways. These results help clarify our understanding of the mechanisms of action of bisphosphonates, potentially opening up new routes to the development of bone resorption, anticancer, and anti-inflammatory drug leads.

Synthesis and polymerase incorporation of β,γ-modified α-L-threofuranosyl thymine triphosphate mimics

Three β,γ-modified α-L-threofuranosyl nucleoside triphosphates were synthesized. The β,γ-modified tTTPs undergo a single incorporation event with HIV RT but undergo multiple incorporations to form full-length product with engineered thermophilic polymeras

An improved method for the synthesis of nucleoside triphosphate analogues

Nucleoside monophosphates, when activated by trifluoroacetic anhydride and N-methylimidazole, efficiently couple with a variety of electron-deficient diphosphonates in a reproducible and efficient manner (72% isolated yield). Unlike traditional methods for the preparation of nucleoside 5′-β,γ-methylenetriphosphate analogues, there is no requirement for predrying, or conversion to specific salt forms, of commercially available nucleoside monophosphate starting materials.

Synthesis of AZT 5′-triphosphate mimics and their inhibitory effects on HIV-1 reverse transcriptase

In search of active nucleoside 5′-triphosphate mimics, we have synthesized a series of AZT triphosphate mimics (AZT P3Ms) and evaluated their inhibitory effects on HIV-1 reverse transcriptase as well as their stability in fetal calf serum and in CEM cell

Nucleotide mimics and their prodrugs

The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Elemental fluorine. Part 9 : Catalysis of the direct fluorination of 2-substituted carbonyl compounds

Catalysis of the reaction between fluorine and a range of 2-substituted carbonyl compounds has been investigated. Most notably, the preparation of diethyl-2-fluoromalonate has been achieved in high yield by fluorination of diethylmalonate in the presence of hydrated copper nitrate. Reactions between fluorine and carbanions derived from 2-substituted carbonyl compounds, including phosphonates, sulphones and nitriles, are also discussed.

Monofluoro- and Difluoro-methylenebisphosphonic Acids: Isopolar Analogues of Pyrophosphoric Acid

New syntheses are described for the preparation of monofluoromethylenebisphosphonic and difluoromethylenebisphosphonic acids whose physical properties show them to be good isopolar analogues of pyrophosphoric acid of significant biological potential.