- Convenient method for the synthesis and some transformations of the lithium salt of bis(diethoxyphosphoryl)fluoromethane
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A convenient method was developed for the synthesis of the lithium salt of 1,1-bis(diethoxyphosphoryl)fluoromethane from available O,O-diethyl (chlorofluoromethyl)phosphonate, and some transformations of the resulting salt were studied.
- Martynov,Sokolov,Aksinenko,Goreva,Epishina,Pushin
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Read Online
- Preparation and characterization of α-fluorinated-γ-aminophosphonates
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Herein we would like to present a synthetic approach to series of α-fluorinated-γ-aminophosphonates, which were prepared by hydrogenolysis of (E)-α-fluorovinylphosphonates. The reaction conditions of hydrogenolysis in the presence of palladium on carbon h
- Ka?mierczak, Marcin,Kubicki, Maciej,Koroniak, Henryk
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Read Online
- RNAI AGENTS FOR INHIBITING EXPRESSION OF HIF-2 ALPHA (EPAS1), COMPOSITIONS THEREOF, AND METHODS OF USE
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The present disclosure relates to RNAi agents, for example, double stranded RNAi agents, able to inhibit HIF-2 alpha ( EPAS1 ) gene expression. Also disclosed are pharmaceutical compositions that include HIF-2 alpha RNAi agents and methods of use thereof. The HIF-2 alpha RNAi agents disclosed herein may be linked or conjugated to targeting ligands (such as compounds that have affinity for integrins, including alpha-v-beta-3 and alpha-v-beta-5 integrins) and pharmacokinetic (PK) enhancers, to facilitate the delivery to cells and tissues, including to clear cell renal cell carcinoma (ccRCC) cells and tumors. Delivery of compositions comprising the HIF-2 alpha RNAi agents in vivo provides for inhibition of HIF-2 alpha gene expression. The HIF-2 alpha RNAi agents can be used in methods of treatment of various diseases and disorders, including ccRCC.
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Paragraph 0240; 0401
(2020/07/25)
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- SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
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Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.
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Paragraph 0724; 0725
(2013/07/05)
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- 1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase
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α-Fluorinated-1,1-bisphosphonic acids derived from fatty acids were designed, synthesized and biologically evaluated against Trypanosoma cruzi, the etiologic agent of Chagas disease, and against Toxoplasma gondii, the agent responsible for toxoplasmosis, and also towards the target parasitic enzymes farnesyl pyrophosphate synthase of T. cruzi (TcFPPS) and T. gondii (TgFPPS). Interestingly, 1-fluorononylidene-1,1-bisphosphonic acid (compound 43) proved to be an extremely potent inhibitor of the enzymatic activity of TgFPPS at the low nanomolar range, exhibiting an IC50 of 30 nM. This compound was two-fold more potent than risedronate (IC50 = 74 nM) that was taken as a positive control. This enzymatic activity was associated with a strong cell growth inhibition against tachyzoites of T. gondii, with an IC50 value of 2.7 μM.
- Szajnman, Sergio H.,Rosso, Valeria S.,Malayil, Leena,Smith, Alyssa,Moreno, Silvia N. J.,Docampo, Roberto,Rodriguez, Juan B.
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experimental part
p. 1424 - 1433
(2012/04/04)
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- α- and β-Substituted phosphonate analogs of LPA as autotaxin inhibitors
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Autotaxin (ATX) is an attractive pharmacological target due to its lysophospholipase D activity which leads to the production of lysophosphatidic acid (LPA). Blockage of ATX produced LPA by small molecules could be a potential anticancer chemotherapy. In our previous study, we have identified the two β-hydroxy phosphonate analogs of LPA (compounds f17 and f18) as ATX inhibitors. With this work, we investigated α- and β-substituted phosphonate analogs of LPA and evaluated them for ATX inhibitory activity. The stereochemistry of β-hydroxy phosphonates was also studied.
- Cui, Peng,McCalmont, William F.,Tomsig, Jose L.,Lynch, Kevin R.,Macdonald, Timothy L.
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p. 2212 - 2225
(2008/09/21)
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- ORALLY AVAILABLE SPHINGOSINE 1-PHOSPHATE RECEPTOR AGONISTS AND ANTAGONISTS
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The present invention relates to S1P analogs that have activity as S1Preceptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure (I) wherein R11 is C5-C18 alkyl or C5-C18 alkenyl; Q is selected from the group consisting of C3-C6 optionally substituted cycloalkyl, C3-C6 optionally substituted heterocyclic, C3-C6 optionally substituted aryl C3-C6 optionally substituted heteroaryl and; R2 is selected from the group consisting of H, C1-C4 alkyl, (C1-C4 alkyl)OH and (C1-C4 alkyl)NH2; R23 is H or C1-C4 alkyl, and R15 is a phosphonate ester or a phosphate ester or a pharmaceutically acceptable salt or tautomer thereof.
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Page/Page column 130-131
(2008/06/13)
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- ANALOGS OF LYSOPHOSPHATIDIC ACID AND METHODS OF MAKING AND USING THEREOF
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Described herein are analogs of lysophosphatidic acid. Also described herein are methods of making and using analogs of lysophosphatidic acid.
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- Synthesis of α-fluorinated phosphonates from α -fluorovinylphosphonates: A new route to analogues of lysophosphatidic acid
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(Matrix presented) A versatile, efficient method for the preparation of α-monofluoromethylene (-CHF-) phosphonates from α -fluorovinylphosphonate provides access to a class of lysophosphatidic acid (LPA) receptor-subtype agonists. In addition, sn-2 O-methylation of α-monofluoromethylene phosphonates using trimethylsilyldiazomethane generated sn-1-acyl, 2-O-methyl α-monofluoromethylene derivatives. Finally, a novel method for the selective etherification of 1,2-diols was developed and a new class of sn-1 O-methyl, 2-acyl α-monofluoromethylene LPA analogues was prepared.
- Xu, Yong,Qian, Lian,Prestwich, Glenn D.
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p. 2267 - 2270
(2007/10/03)
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- The preparation of (EtO)2P(O)CFHZnBr and (EtO)2P(O)CFHCu and their utility in the preparation of functionalized α-fluorophosphonates
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The organometallic reagent, (EtO)2P(O)CFHZnBr, was generated in situ in excellent yields via the reaction of (Eto)2P(O)CFHBr with zinc metal. Metathesis with Cu(I)Br gave (EtO)2P(O)CFHCu. The reagents exhibit excellent reactivity with substrates, such as allyl halides, alkynyl halides, vinyl halides, aryl halides and acyl or phosphoryl halides, and provide a useful one flask route to functionalized α-fluorophosphonates.
- Zhang, Xin,Weiming, Qiu,Burton, Donald J.
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p. 2681 - 2684
(2007/10/03)
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- Synthesis of new PMEA diphosphate mimics
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We synthesized and characterized new diphosphate mimics of the acyclic nucleotide phosphonate PMEA [Adefovir, 9-(2-phosphonylmethoxyethyl)adenine].
- Laux,Perigaud,Imbach,Gosselin
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p. 1003 - 1004
(2007/10/03)
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- Synthesis of a potent inhibitor of HIV reverse transcriptase
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The newly synthesised P(β),-P(γ)-difluoromethylenebisphosphonate analogue 2 of nor-carbovir triphosphate is a potent inhibitor of HIV reverse transcriptase; it also exhibits a greatly enhanced stability to dephosphorylation, in foetal blood serum, relative to AZTTP and other nucleoside triphosphates.
- Hamilton, Chris J.,Roberts, Stanley M.,Shipitsin, Alexander
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p. 1087 - 1088
(2007/10/03)
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- An efficient synthesis of tetraethyl fluoromethylenediphosphonate and derivatives from diethyl dibromofluoromethylphosphonate
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Treatment of diethyl 1,1-dibromo-1-fluoromethylphosphonate with n-BuLi (1:1) at low temperature affords by self-trapping in quantitative yield the lithiated derivative of tetraethyl fluoromethylenediphosphonate which is reacted with alkylating and halogenating agents or converted with high selectivity into (E) diethyl fluorovinylphosphonates by reaction with carbonyl compounds.
- Iorga, Bogdan,Eymery, Frederic,Savignac, Philippe
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p. 4477 - 4480
(2007/10/03)
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- Syntheses of some fluorine-containing halomethanephosphonate and methylenebisphosphonate esters
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The Michaelis-Becker reaction between diethyl sodiophosphite and either of the halofluoromethanes CF2Cl2 and CF3Br gives tetraethyl difluoromethylenebisphosphonate.By contrast, the corresponding reaction with CFCl3 gives not only diethyl dichlorofluoromethanephosphonate but also teraethyl prophosphate as the major product.Diethyl dichlorofluoromethanephosphonate, readily prepared by a normal Arbusov reaction from+ CCl3F, reacts with diethyl sodiophosphite to give tetraethyl fluoromethylenebisphosphonate thereby providing a simple efficient, and inexpensive synthesis of this useful material.
- Blackburn, G. Michael,Taylor, Graham E.
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