cas 770-12-7, Phenyl dichlorophosphate | Articles data

Articles about 770-12-7Total 53 be found

Article title
Article abstract
Author
Journal number and time
Download

Prodrug compound and application ofprodrug compound in treatment of cancer
The present invention provides a compound indicated by a formula (I), pharmaceutically acceptable salts or esters thereof, a pharmaceutical composition of the compound, and application of the compoundand the pharmaceutical composition in the inhibition or regulation of the activity of tyrosine kinase and treating disease symptoms or symptoms including cancer mediated by tyrosine kinase.
-
Paragraph 0140-0141

(2021/03/06)

PRODRUGS OF THE TYROSINE KINASE INHIBITOR FOR TREATING CANCER
There are provided compounds of Formula (I), and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, useful for inhibition or modulation of the activity of tyrosine kinases and treatment of disease states or conditions mediated by tyrosine kinases, including cancers. (I)
-
Paragraph 00101-00102

(2021/03/05)

Organophosphorous phenyl phosphates: Synthesis, dye/protein interactions and antimicrobial evaluation
A series of Phenyl Phosphates (PPs) has been synthesized and characterized with FTIR spectroscopy. PPs, the product of the reaction of phenol and phosphoryl chloride followed by hydrolysis having larger number of hydrophilic hydroxyl groups, used for the dye interaction and antimicrobial activities. Interaction of PPs with 1,2-diphenyldiazene and 4-(phenyldiazene)phenol were studied through UV/ Vis method where observed hypochromic effect has revealed the dye adsorption property of PPs. Similarly PPs have shown the interaction with bovine serum and human serum albumins where the weaker interaction observed with later. Antimicrobial in vitro evaluation has been assessed on the basis of zone of inhibition with six bacterial (gram +ve and –ve) strains. Since PPs were found very active so minimal inhibitory concentration (MIC) analysis was done where all PPs have shown MIC less than 5 μg/mL. Due to high number of hydroxyl groups PPs have shown good interactions with biomolecules and cell wall of bacteria therefore this impression has predicted their future in medicinal field.
Ameta, Rakesh Kumar,Duan, Yongtao,Koshti, Rohit R.,Muddassir, Mohd.,Patel, Amee S.,Trivedi, Nidhi S.,Vyas, Akshay
(2021/01/09)

BI- AND MONOCYCLIC NUCLEOSIDE ANALOGS FOR TREATMENT OF HEPATITIS E
The present disclosure is directed toward bi- and monocyclic nucleoside analogs, and compositions comprising these compounds for use in the treatment of hepatitis E infections.
-
Page/Page column 35; 43

(2021/10/22)

Preparation method of pentaerythritol diphosphate
The invention relates to the technical field of organic synthesis, and provides a preparation method of pentaerythritol diphosphate. The phosphoryl dichloride compound is prepared from a phenolic compound and phosphorus oxychloride under the condition of a catalyst, the yield of the phosphoryl dichloride compound is high, the activity of the phosphoryl dichloride compound is high, and the next step of reaction can be directly carried out without drying; then the phosphoryl dichloride compound is reactd with pentaerythritol under the vacuum pressure reduction condition, acid generated in the reaction can be rapidly removed under the vacuum pressure reduction condition, and the reaction can be carried out in the forward direction; furthermore, a phosphoryl dichloride compound is dropwise added, after dropwise adding is completed, esterification can be completed basically by one acyl chloride, and at the moment, an acid-binding agent is added, so that esterification of a second acyl chloride is facilitated, and the reaction time is greatly shortened; and the reaction temperature can be reduced under the vacuum decompression condition, the problems of acidolysis of pentaerythritol diphosphate and reaction with hydrogen chloride are avoided, the reaction safety and operability are improved, and the reaction efficiency is improved.
-
Paragraph 0032; 0044-0045; 0047-0048; 0050-0051

(2020/09/12)

A Phosphoramidate Strategy Enables Membrane Permeability of a Non-nucleotide Inhibitor of the Prolyl Isomerase Pin1
The membrane permeability of nucleotide-based drugs, such as sofosbuvir (Sovaldi), requires installation of phosphate-caging groups. One strategy, termed "ProTide", masks the anionic phosphate through an N-linked amino ester and an O-linked aromatic phospho-ester, such that release of the active drug requires consecutive enzymatic liberation by an esterase and then a phosphoramidase, such as Hint1. Because Hint1 is known to be selective for nucleotides, it was not clear if the ProTide approach could be deployed for non-nucleotides. Here, we demonstrate that caging of a phosphate-containing inhibitor of the prolyl isomerase Pin1 increases its permeability. Moreover, this compound was processed by both esterase and phosphoramidase activity, releasing the active molecule to bind and inhibit Pin1 in cells. Thus, Hint1 appears to recognize a broader set of substrates than previously appreciated. It seems possible that other potent, but impermeable, phosphate-containing inhibitors might likewise benefit from this approach.
Schwarz, Daniel M. C.,Williams, Sarah K.,Dillenburg, Maxwell,Wagner, Carston R.,Gestwicki, Jason E.
supporting information
p. 1704 - 1710
(2020/09/02)

Compound for treating metabolic diseases as well as preparation method and application thereof
The invention provides a compound for treating metabolic diseases, the compound has a structure represented by formula (I) or formula (II), or a racemate, a stereoisomer, a geometric isomer, a tautomer, a solvate, a hydrate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. The compounds provided by the invention are FXR and/or TGR5 receptor activators, and the compounds havethe activity of activating FXR and/or TGR5 receptors, and can be used for preparing medicines for treating chronic liver diseases, metabolic diseases or portal hypertension.
-
Paragraph 0170-0173

(2019/07/04)

Polyfluoroaromatic stavudine (d4T) ProTides exhibit enhanced anti-HIV activity
Human Immunodeficiency Virus (HIV) damages the immune system and leads to the life-threatening acquired immunodeficiency syndrome (AIDS). Despite the advances in the field of antiretroviral treatment, HIV remains a major public health challenge. Nucleosides represent a prominent chemotherapeutic class for treating viruses, however their cellular uptake, kinase-mediated activation and catabolism are limiting factors. Herein, we report the synthesis and in vitro evaluation of stavudine (d4T) ProTides containing polyfluorinated aryl groups against two strains; HIV-1 (IIIB) and HIV-2 (ROD). ProTide 5d containing a meta-substituted pentafluorosulfanyl (3-SF5) aryl group showed superior antiviral activity over the parent d4T and the nonfluorinated analogue 5a. ProTide 5d has low nanomolar antiviral activity; (IC50 = 30 nM, HIV-1) and (IC50 = 36 nM, HIV-2) which is over tenfold more potent than d4T. Interestingly, ProTide 5d showed a significantly high selectivity indices with SI = 1753 (HIV-1) and 1461 (HIV-2) which is more than twice that of the d4T. All ProTides were screened in wild type as well as thymidine kinase deficient (TK?) cells. Enzymatic activation of ProTide 5d using carboxypeptidase Y enzyme and monitored using both 31P and 19F NMR is presented.
Kandil, Sahar,Pannecouque, Christophe,Chapman, Fiona M.,Westwell, Andrew D.,McGuigan, Christopher
supporting information

(2019/11/13)

NUCLEOSIDE PHOSPHATE COMPOUND AND PREPARATION METHOD AND USE THEREOF
Provided in the present invention are a compound of Formula (I), a pharmaceutical composition comprising the same, a method for preparing the same, and use thereof as a NS5B polymerase inhibitor, a DNA polymerase inhibitor or a reverse transcriptase inhibitor for the prevention or treatment of viral diseases or cancers.
-
Paragraph 0178-0179; 0182-0183

(2019/11/14)

Exploration of chiral Lewis acid Mg2+ catalysts in the synthesis of aryl organophosphate triesters from phosphorus oxychloride through a three-step, two-pot substitution sequence
A variety of nucleophilic and Lewis acid catalysts were examined for use in promoting the synthesis of organophosphate triesters. Eight novel organophosphate triesters are reported here for the first time. MgSO4 was discovered as an inexpensive catalyst capable of improving the synthesis of a variety of aryl organophosphate triesters from the readily available and low cost precursor phosphorus oxychloride in a three-step, two-pot sequence. Yields for this method improve upon the uncatalyzed method by 8–36%. Several chiral catalysts were tested, but none were able to induce enantioselectivity in the reaction.
Granger, Emily,Solomianko, Katarzyna,Young, Cori,Erb, Jeremy
supporting information
p. 1404 - 1408
(2018/03/13)

Preparation method of low-triphenyl phosphate engineering plastic halogen-free flame retardant
The invention belongs to the technical field of applied engineering plastics, and in particular, relates to a preparation method of a low-triphenyl phosphate engineering plastic halogen-free flame retardant. The method comprises the steps: under the action of a Lewis catalyst, carrying out a reaction of phenol with phosphorus oxychloride, reducing the pressure and distilling out excess phosphorusoxychloride, to obtain a mixture intermediate; carrying out a condensation reaction of the mixture intermediate and p-dihydroxybenzene, carrying out a reaction of the mixed intermediate with a properamount of p-dihydroxybenzene firstly, after a part of p-dihydroxybenzene is completely reacted, carrying out high vacuum dehydrochlorination, then adding triethylamine and the remaining p-dihydroxybenzene at relatively low temperature, and carrying out a reaction, wherein increase of the content of triphenyl phosphate is greatly reduced, toxicity to human bodies is reduced, and at the same time, the purity and the yield of the product are improved; and the preparation method has the advantages of simple process operation, short production cycle, economy and environmental protection, can satisfy the requirements of industrial scale production, and is suitable for industrialized popularization and application.
-
Paragraph 0015; 0016; 0017; 0018; 0019; 0020; 0022; 0024

(2018/03/28)

Nucleoside phosphamide compound and preparation method and application of nucleoside phosphamide in medicine
The invention provides a nucleoside phosphamide compound shown as a formula (I), and an application of the compound as an antiviral drug. The compound can inhibit replication of RNA virus, and can be used as an inhibitor for hepatitis c virus (HCV)NS5B polymerase. The compound has inhibiting effect for NS5B polymerase and has little toxicity on hepatic cells.
-
Paragraph 1059; 1060; 1061

(2017/04/29)

Kinetin Riboside and Its ProTides Activate the Parkinson’s Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization
Since loss of function mutations of PINK1 lead to early onset Parkinson’s disease, there has been growing interest in the discovery of small molecules that amplify the kinase activity of PINK1. We herein report the design, synthesis, serum stability, and hydrolysis of four kinetin riboside ProTides. These ProTides, along with kinetin riboside, activated PINK1 in cells independent of mitochondrial depolarization. This highlights the potential of modified nucleosides and their phosphate prodrugs as treatments for neurodegenerative diseases.
Osgerby, Laura,Lai, Yu-Chiang,Thornton, Peter J.,Amalfitano, Joseph,Le Duff, Cécile S.,Jabeen, Iqra,Kadri, Hachemi,Miccoli, Ageo,Tucker, James H. R.,Muqit, Miratul M. K.,Mehellou, Youcef
p. 3518 - 3524
(2017/05/05)

Reactivity of Ferrocenyl Phosphates Bearing (Hetero-)Aromatics and [3]Ferrocenophanes toward Anionic Phospho-Fries Rearrangements
The temperature-dependent behavior within anionic phospho-Fries rearrangements (apFr) of P(O)(OFc)n(EAr)3-n (Fc = Fe(η5-C5H5)(η5-C5H4); E = O; Ar = phenyl, naphthyls, (R)-BINOL, [3]ferrocenophanyl; E = N, 1H-pyrrolyl, 1H-indolyl, 9H-carbazolyl; n = 1-3) is reported. While Fc undergoes one, the Ph-based apFr depends on temperature. First, the aryls are lithiated and rearranged, followed by Fc and N-heterocycles. Addition of Me2SO4 thus gave methylated Fc, contrary to non-organometallic aromatics giving mixtures of HO and MeO derivatives. The (R)-BINOL Fc phosphate gave Fc-rearranged phosphonate in 91% de. Exchanging O- with N-aliphatics prevented apFr, due to higher electron density at P. Also 1,2-N→C migrations were observed. X-ray analysis confirms 1D H bridge bonds for OH and NH derivatives. The differences in reactivity between N-aliphatic and N-aromatic phosphoramidates were verified by electrochemistry. The redox potentials revealed lower values for the electron-rich aliphatics, showing no apFr, preventing a nucleophilic attack at P after lithiation. Redox separations for multiple Fc molecules are based on electrostatic interactions.
Korb, Marcus,Lehrich, Steve W.,Lang, Heinrich
p. 3102 - 3124
(2017/03/23)

NICOTINAMIDE RIBOSIDE AND NICOTINAMIDE MONONUCLEOTIDE DERIVATIVES FOR USE IN THE TREATMENTS OF MITOCHONDRIAL-RELATED DISEASES
Provided herein are compounds of Formula (I): or a pharmaceutically acceptable salt thereof, and compositions comprising such compounds that are useful for increasing the amount of NAD+ in cells. Also disclosed are methods of using the disclosed compounds and compositions for treating mitochondrial-related diseases or disorders.
-
Page/Page column 34

(2017/06/20)

URACIL NUCLEOTIDE ANALOGUES, THEIR PREPARATION METHOD AND USE THEREOF
The invention relates to uracil nucleotide analogues, their preparation method and use thereof. Specifically, the invention provides the uracil nucleotide analogues with the formula (I), their stereoisomers and pharmaceutical acceptable salts, the preparation method and use. These compounds are RNA-dependent RNA viral replication inhibitors, and can be used as HCV NS5B polymerase inhibitors, HCV replication inhibitors as well as for the treatment of hepatitis C infection in mammals. They have broad application prospects and are expected to develop a new generation of antiviral drugs.
-
Page/Page column 111; 112

(2016/10/08)

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.
-
Paragraph 0979

(2015/04/21)

β-D-2′-C-methyl-2,6-diaminopurine ribonucleoside phosphoramidates are potent and selective inhibitors of hepatitis C virus (HCV) and are bioconverted intracellularly to bioactive 2,6-diaminopurine and guanosine 5′-triphosphate forms
The conversion of selected β-d-2,6-diaminopurine nucleosides (DAPNs) to their phosphoramidate prodrug (PD) substantially blocks the conversion to the G-analog allowing for the generation of two bioactive nucleoside triphosphates (NTPs) in human hepatocytes. A variety of 2′-C-methyl DAPN-PDs were prepared and evaluated for inhibition of HCV viral replication in Huh-7 cells, cytotoxicity in various cell lines, and cellular pharmacology in both Huh-7 and primary human liver cells. The DAPN-PDs were pan-genotypic, effective against various HCV resistant mutants, and resistant variants could not be selected. 2′-C-Me-DAPN-TP and 2′-C-Me-GTP were chain terminators for genotype 1b HCV-pol, and single nucleotide incorporation assays revealed that 2′-C-Me-DAPN-TP was incorporated opposite U. No cytotoxicity was observed with our DAPN-PD when tested up to 50 μM. A novel, DAPN-PD, 15c, has been selected for further evaluation because of its good virologic and toxicologic profile and its ability to deliver two active metabolites, potentially simplifying HCV treatment.
Zhou, Longhu,Zhang, Hong-Wang,Tao, Sijia,Bassit, Leda,Whitaker, Tony,Mcbrayer, Tamara R.,Ehteshami, Maryam,Amiralaei, Sheida,Pradere, Ugo,Cho, Jong Hyun,Amblard, Franck,Bobeck, Drew,Detorio, Mervi,Coats, Steven J.,Schinazi, Raymond F.
p. 3445 - 3458
(2015/05/05)

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Coronaviridae virus, a Togaviridae virus, a Hepeviridae virus and/or a Bunyaviridae virus infection with one or more nucleosides, nucleotides and nucleotide analogs.
-
Paragraph 0883; 0900

(2016/03/08)

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.
-
Paragraph 0833; 0850

(2016/03/11)

FLAME RETARDANT COMPRISING AROMATIC PHOSPHATE ESTER-BASED COMPOUND, AND METHOD FOR PREPARING SAME
A method for preparing a novel aromatic phosphate ester-based compound, including: (a) reacting a compound expressed by chemical formula 1 (i) and a C6-10 aryl compound substituted with hydroxy or C1-6 alkoxy, or a C6-20 arylalkyl compound substituted with hydroxy or C1-6 alkoxy (ii), which are used as reaction materials by gradually heating to the temperature levels of 90-125° C., 125-180° C., 180-210° C. and 210-240° C.; (b) separating an aromatic phosphate ester-based compound from the resultant product in step (a) under the condition of a pressure of 0.01 mmHg-50 mmHg and a temperature of 50° C.-300° C. using fractional distillation; and (c) reacting the aromatic phosphate ester-based compound separated in step (b) (i) and C1-10 alcohol or a nitrogen compound (ii) at a temperature of 10-70° C.
-
Paragraph 0149-0158

(2015/11/10)

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.
-
Paragraph 0504

(2014/07/08)

2′-Fluoro-6′-methylene-carbocyclic adenosine phosphoramidate (FMCAP) prodrug: In vitro anti-HBV activity against the lamivudine-entecavir resistant triple mutant and its mechanism of action
Novel 2′-fluoro-6′-methylene-carbocyclic adenosine (FMCA) monophosphate prodrug (FMCAP) was synthesized and evaluated for its in vitro anti-HBV potency against a lamivudine-entecavir resistant clone (L180M + M204V + S202G). FMCA demonstrated significant antiviral activity against wild-type as well as lamivudine-entecavir resistant triple mutant (L180M + M204V + S202G). The monophosphate prodrug (FMCAP) demonstrated greater than 12-fold (12×) increase in anti-HBV activity without increased cellular toxicity. Mitochondrial and cellular toxicity studies of FMCA indicated that there is no significant toxicity up to 100 μM. Mode of action studies by molecular modeling indicate that the 2′-fluoro moiety by hydrogen bond as well as the Van der Waals interaction of the carbocyclic ring with the phenylalanine moiety of the polymerase promote the positive binding, even in the drug-resistant mutants.
Rawal, Ravindra K.,Singh, Uma S.,Chavre, Satish N,Wang, Jianing,Sugiyama, Masaya,Hung, Wai,Govindarajan, Rajgopal,Korba, Brent,Tanaka, Yasuhito,Chu, Chung K.
p. 503 - 506
(2013/02/25)

[RuIV(F20-TPP)Cl2]efficiently catalysed inter- and intra-molecular nitrene insertion into sp3 C-H bonds of hydrocarbons using phosphoryl azides as nitrene sources
[RuIV(F20-TPP)Cl2][H2(F 20-TPP) = meso-tetrakis(pentafluorophenyl)porphyrin] is an active catalyst for both inter- and intra-molecular nitrene insertion into sp 3 C-H bonds of hydrocarbons in good to high product yields using phosphoryl azides as nitrene sources. The Royal Society of Chemistry 2013.
Xiao, Wenbo,Wei, Jinhu,Zhou, Cong-Ying,Che, Chi-Ming
supporting information
p. 4619 - 4621
(2013/06/04)

Palladium-catalyzed ortho-alkenylation of aryl hydrogen phosphates using a new mono-phosphoric acid directing group
A highly efficient Pd-catalyzed ortho-alkenylation is reported using a mono-phosphoric acid-directing group for the first time. This phosphoric acid-directing group is successfully utilized for the synthesis of various alkenylated products and offers a new approach to transition-metal-catalyzed C-H activation. The Royal Society of Chemistry 2013.
Chan, Li Yan,Kim, Sunggak,Ryu, Taekyu,Lee, Phil Ho
supporting information
p. 4682 - 4684
(2013/06/04)

Pd(II)-catalyzed ortho-arylation of aryl phosphates and aryl hydrogen phosphates with diaryliodonium triflates
Functionalized biaryl compounds were successfully synthesized using phosphates as the ortho-directing group in the Pd(II)/Pd(IV) catalytic cycle.
Chan, Li Yan,Cheong, Lilian,Kim, Sunggak
supporting information
p. 2186 - 2189
(2013/06/05)

Synthesis of some cyclophosphorodiamidates derivatives of bis(2-chloroethyl)amine
Phenyl phosphorodichloridate (1) is readily prepared by reaction of phenol with phosphoryl chloride at low temperature. The crude product is white in colour is subjected to vacuum distillation. However, this reagent reacts only poorly with bis(2-chloroethyl)amine hydrochloride at ambient temperature; thus, an alternative route was sought to aniline and to give 2 and 3, respectively compounds. Compound (3) reacted with aniline and diazabicyclo[2,2,2]octane in refluxing toluene to give 4. Reaction of 3 with diazabicyclo[2,2,2]octane and potassium tert-butoxide in refluxing toluene gave 5 and 6, respectively which compound 6 arised from elimination of HCl from the 2-chloroethyl group of compound 5. Reactions proceed in high yield, under mild conditions. The structures of prepared compounds were confirmed by 1H, 31P and 13C NMR spectroscopy, mass spectrometry and X-ray crystallography.
Jalalifar, Mahdi,Khalikov, Shirinbek,Javidan, Abdollah
p. 5985 - 5988
(2013/07/26)

Synthesis of ethyl and phenyl amido(ethoxyphenylalaninyl)phosphate compounds
The synthetic route for preparation of three phosphoramides containing amino acid and their precursors in good yield and mild conditions is reported. This involved the synthesis of the ethyl and phenyl phosphorodichloridate and its reaction with bis(β-chloroethyl) amine or diethylamine, followed by the reaction of the products with phenyl alanine ethyl ester hydrochloride. In all the three compounds, because of the presence of chiral centre, the final products were obtained as a mixture of two diastereoisomers, which can be determined using 31P NMR and TLC methods. The structures of all the prepared compounds were confirmed by 1H NMR, 31P NMR, 13C NMR spectroscopy.
Jalalifar,Javidan,Khalikov
experimental part
p. 1097 - 1100
(2012/10/07)

Synthesis, characterization and thermal studies of cresol based polyphosphate esters
Polyphosphate esters were synthesized from cresol phosphorodichloridates and dihydric phenols by interfacial polycondensation using a phase transfer catalyst. The polymers were characterized by IR, 1H and 31P NMR spectroscopy and GPC. The thermal stability of the polymers was determined by thermogravimetry.
Antony, Rosy,Ravindran, Sumisha,Mary
p. 701 - 703
(2012/10/29)

COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTION
The present invention describes compounds of formulae I and II and methods for treating viral infection, such as Flaviviridae virus infection, including Hepatitis C infection (HCV).
-
Page/Page column 88

(2010/12/18)

Synthesis of the novel phosphoramidate derivatives of Chrysin
A novel type of phosphoramidate derivatives of chrysin were synthesized by a facile phosphorylation reaction. The structures of all the newly synthesized chrysin derivatives were confirmed by ESI MS, HR MS, NMR, and IR.
Chen, Xiaolan,Yuan, Jinwei,Zhang, Shouren,Qu, Lingbo,Zhao, Yufen
experimental part
p. 274 - 278
(2010/06/19)

PHOSPHORAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INFECTIONS
Phosphoramidate compounds derived from guanine bases having enhanced therapeutic potency are provided, and these compounds in particular have enhanced potency with respect to treatment of viral infections, such as hepatitis C virus. Pharmaceutical compositions, methods of preparing the compounds, and methods of using the compounds and compositions to treat viral infections are also provided.
-
Page/Page column 88-89

(2010/08/04)

Synthesis of a novel type of phosphoramidate derivatives of 2-arylquinolone
A novel type of phosphoramidate derivatives of 2-arylquinolone were synthesized through a facile phosphorylated reaction for the first time. The structure of these compounds was elucidated by IR, HR MS, NMR and X-ray. Synthesis and structural characterization of the titled compounds was discussed.
Yuan, Jin-Wei,Chen, Xiao-Lan,Qu, Ling-Bo,Qu, Zhi-Bo,Zhou, Ya-Dong,Zhao, Yu-Fen
experimental part
p. 51 - 58
(2010/04/05)

Synthesis and biological evaluation of LNA phosphoramidates
The synthesis of LNA phosphoramidates is presented. The LNA phosphoramidates were evaluated for their ability to inhibit cell proliferation of the human prostate cancer cell line 15PC3. A number of the LNA phosphoramidates showed cell proliferation inhibition determined by the MTS assay. Copyright Taylor & Francis Group, LLC.
Jensen, Jacob,Sjogren, Gitte,Hansen, Jens Bo,Rosenbohm, Christoph,Koch, Troels
p. 37 - 42
(2008/09/18)

Design, synthesis, and biological evaluation of phosphoramide derivatives as urease inhibitors
The design, synthesis, and biological evaluation of phosphoramide derivatives as urease inhibitors to reduce the loss of ammonia has been carried out. Forty phosphorus derivatives were synthesized and their inhibitory activities evaluated against that of jack bean urease. In addition, in vivo assays have been carried out. All of the compounds were characterized by IR, 1H NMR, MS, and elemental microanalysis. In some cases, detailed molecular modeling studies were carried out, and these highlighted the interaction between the enzyme active center and the compounds and also the characteristics related to their activity as urease inhibitors. According to the IC50 values for in vitro inhibitory activity, 12 compounds showed values below 1 μM and 8 of them represent improvements of activity in comparison to the commercial urease inhibitor N-n-butylthiophosphorictriamide (NBPT) (100 nM) (AGROTAIN). On the basis of the activity results and the conclusions of the molecular modeling study, a structural model for new potential inhibitors has been defined.
Dominguez, Maria J.,Sanmartin, Carmen,Font, Maria,Palop, Juan A.,San Francisco, Sara,Urrutia, Oscar,Houdusse, Fabrice,Garcia-Mina, Jose M.
scheme or table
p. 3721 - 3731
(2010/03/05)

Activation of p16 gene silenced by DNA methylation in cancer cells by phosphoramidate derivatives of 2′-deoxyzebularine
We report herein the application of the phosphoramidate ProTide technology to improve the metabolism of the DNA methytransferase inhibitor, zebularine (Z). Zebularine is a riboside that must undergo a complex metabolic transformation before reaching the critical 2′-deoxyzebularine 5′-triphosphate (dZTP). Because 2′-deoxyzebularine (dZ) is not phosphorylated and therefore inactive, the ProTide strategy was employed to bypass the lack of phosphorylation of dZ and the inefficient reduction of zebularine 5′-diphosphate by ribonucleotide-diphosphate reductase required for zebularine. Several compounds were identified as more potent inhibitors of DNA methylation and stronger inducers of p16 tumor suppressor gene than zebularine. However, their activity was dependent on the administration of thymidine to overcome the potent inhibition of thymidylate synthase (TS) and deoxycytidine monophosphate (dCMP) deaminase by dZMP, which deprives cells of essential levels of thymidine. Intriguingly, the activity of the ProTides was cell line-dependent, and activation of p16 was manifest only in Cf-Pac-1 pancreatic ductal adenocarcinoma cells.
Yoo, Christine B.,Valente, Rocco,Congiatu, Costantino,Gavazza, Federica,Angel, Annette,Siddiqui, Maqbool A.,Jones, Peter A.,McGuigan, Christopher,Marquez, Victor E.
experimental part
p. 7593 - 7601
(2009/12/07)

Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives
We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.
McGuigan, Christopher,Hassan-Abdallah, Alshaimaa,Srinivasan, Sheila,Wang, Yikang,Siddiqui, Adam,Daluge, Susan M.,Gudmundsson, Kristjan S.,Zhou, Huiqiang,McLean, Ed W.,Peckham, Jennifer P.,Burnette, Thimysta C.,Marr, Harry,Hazen, Richard,Condreay, Lynn D.,Johnson, Lance,Balzarini, Jan
p. 7215 - 7226
(2007/10/03)

THERAPEUTIC FUROPYRIMIDINES AND THIENOPYRIMIDINES
The invention provides compounds of formula I, II, and III as described herein, as well as pharmaceutical compositions comprising the compounds, and synthetic methods and intermediates that are useful for preparing the compounds. The compounds of formula I, II, and III are useful as anti-viral agents and/or as anti-cancer agents.
-
Page/Page column 125

(2008/06/13)

Anti-proliferative and anti-leukemic activity of DDE46 (compound WHI-07), a novel bromomethoxylated arylphosphate derivative of zidovudine, and related compounds: Studies using human acute lymphoblastic leukemia cells and the zebrafish model
The anti-proliferative effects of a novel bromomethoxylated arylphosphate derivative of zidovudine (compound DDE46, CAS 213982-96-8) were first examined in a zebra fish embryo model. DDE46 blocked the cell division at the 2-cell stage of the embryonic development followed by total cell fusion. DDE46 also inhibited the proliferation of the leukemic cell lines NALM-6 and MOLT-3. DDE46 enhanced the activity of the pro-apoptotic enzymes Caspase-3, Caspase-6, Caspase-8, and Caspase-9 leading to the apoptotic death of the leukemic cell line Jurkat. These results justify the further development of this agent as a new anti-leukemic drug candidate. ECV · Editio Cantor Verlag, Aulendorf (Germany).
Benyumov, Alexey O.,Venkatachalam, Taracad K.,Grigoriants, Olga O.,Vassilev, Alexei O.,Tibbles, Heather E.,Downs, Suzanne,Dumez, Darin,Uckun, Fatih M.
p. 114 - 122
(2007/10/03)

Syntheses and spectral characterization of 2-aryloxy - 5,5′- bis(bromomethyl)-1,3,2P-dioxaphosphorinane 2-oxides
2-Aryloxy-5,5′-bis(bromomethyl)-1,3,2-dioxaphosphorinane 2-oxides 3 have been synthesized by the reaction of 2,2′-bis(bromomethyl)-1,3- propanediol 1 with various arvlphosphorodichloridates 2a-h in the presence of triethylamine in dry tetrahydrofuran at room temperatuure. Their 1H, 13C, 31P NMR and mass spectral data are discussed.
Stephen Babu,Anasuyamma,Venugopal,Naga Raju,Suresh Reddy
p. 1248 - 1251
(2007/10/03)

Synthesis of some new chiral bifunctional o-hydroxyarylphosphonodiamides and their application as ligands in Ti(IV) complex catalyzed asymmetric silylcyanation of aromatic aldehydes
Some new chiral bifunctional o-hydroxyarylphosphonodiamides were synthesized starting from (+)-cis-1,2,2-trimethylcyclopentane-1,3-diamine and the absolute configuration of the phosphorus atom was determined by X-ray diffraction analysis. Excellent enantioselectivity (up to 98% ee) was achieved in asymmetric silylcyanation of aromatic aldehydes using a chiral titanium complex formed in situ from Ti(OiPr)4 and o-hydroxyarylphosphonodiamide as the catalyst. Graphical Abstract.
He, Ke,Zhou, Zhenghong,Wang, Lixin,Li, Kangying,Zhao, Guofeng,Zhou, Qilin,Tang, Chuchi
p. 10505 - 10513
(2007/10/03)

Aryl phosphate derivatives of d4T having anti-HIV activity
Aryl phosphate derivatives of d4T with para-bromo substitution on the aryl group show markedly increased potency as anti-HIV agents without undesirable levels of cytotoxic activity. In particular, these derivatives are potent inhibitors of HIV reverse transcriptase. In a preferred aspect of the present invention, the phosphorus of the aryl phosphate group is further substituted with an amino acid residue that may be esterified or substituted, such as a methoxy alaninyl group.
-
Page column 14

(2008/06/13)

Synthesis of chiral 2-oxo- and 2-thio-1,3,2-oxazaphospho-lidines via the asymmetric cyclization of l-serinoates with (thio)phosphoryl dichlorides
In this paper is described the asymmetric cyclization of L-serine derivatives with phosphoro(no-)dichloridates or their thio-analogues, and investigated the asymmetric induction effect of chiral carbon centre on the forming chiral phosphorus centre. Some cyclization products have been separated as a pure diastereomer and their configuration is preliminarily discussed.
He, Zheng-Jie,Chen, Wen-Bin,Zhou, Zheng-Hong,Tang, Chu-Chi
p. 3473 - 3479
(2007/10/03)

Studies on chiral thiophosphoric acids and their derivatives 16. - The asymmetric cyclization of L-(+)-prolinol with (thio)phosphoro(-no)dichloridates
The cyclizations of L-(+)-prolinol 5 with (thio)phosphoro(-no)dichloridates 6 give 1,2,3-azaphosphaoxabicyclo[3.3.0]octanes 7 consisting of unequal amounts of diastereoisomers, eight pairs of which have been successfully resolved by silica gel column chromatography or recrystallization. The influences of reaction temperature, solvent and substrate concentration upon the asymmetric induction have also been investigated.
He, Zheng-Jie,Wang, You-Ming,Tang, Chu-Chi
p. 59 - 66
(2007/10/03)

Intracellular delivery of bioactive AZT nucleotides by aryl phosphate derivatives of AZT
Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective anti-HIV activity in CEM cells; the magnitude of the biological effect varied considerably depending on the nature of the phosphate blocking group. Moreover, several of the compounds retain marked antiviral activity in TK- (thymidine kinase-deficient) mutant CEM cells in which AZT was virtually inactive. These data strongly support the hypothesis that the AZT phosphate derivatives exert their biological effects via intracellular release of AZT nucleotide forms and suggest that the potential of nucleoside drugs in antiviral chemotherapy may be enhanced by suitable nucleotide delivery strategies.
McGuigan,Pathirana,Balzarini,De Clercq
p. 1048 - 1052
(2007/10/02)

Synthesis of aryl dichlorophosphates using phase transfer catalysts
Synthesis of aryl dichlorophosphates has been carried out using phase transfer method.Two strategies, one involving solid-liquid and the other liquid-liquid phase transfer catalysts, have been used to synthesize phenyl, p-nitrophenyl and o-chlorophenyl phosphorodichloridates.In either case, the phenoxide ions are carried from the solid or aq. phase with the help of a phase transfer catalyst into the organic phase where the reaction with phosphoryl chloride occurs efficiently.A possible mechanism has been proposed.
Rathore, M.,Kabra, A.,Rani, P.,Narang, C. K.,Mathur, N. K.
p. 1066 - 1067
(2007/10/02)

ESTERIFICATION KINETICS OF PHENOL WITH PHOSPHORYL TRICHLORIDE
The liquid-phase esterification kinetics of phenol with POCl3 has been studied at isothermal conditions within the temperature interval from 90 to 110 deg C.The esterification rate constants of the first, second, and third esterification steps and the activation energies of these steps have been calculated.The given system of competitive consecutive reactions can be described by a system of differential equations which has been solved by the Gauss-Newton optimization method of non-linear regression in the Marquardt modification.In the sequence of the first, second, and third step the esterification rate constants have been found to gradually decrease, whereas the activation energies increase in the same sequence.
Magura, Miroslav,Vojtko, Jan,Zemanova, Eva,Kaszonyi, Alexander,Ilavsky, Jan
p. 608 - 615
(2007/10/02)

Ozonization: An Efficient Method for the Oxidation of Halophosphines
The ozonization of various halophosphines 1a-j leads with quantitative yields to the corresponding phosphine oxides 2a-j.Ozonization is a convenient method of oxidation, in particular of compounds with bulky ligands (1c, 1d, 1e).
Caminade, Anne-Marie,El Khatib, Fayez,Baceiredo, Antoine,Koenig, Max
p. 365 - 368
(2007/10/02)

"Chemistry and Biochemistry of Helminths". Part 1. The Use of 1,3,2-Oxazaphospholidin-2-ones in the Synthesis of Alkoxy and Aryloxyphosphorylethanolamine Derivatives.
-
Euerby, Melvin R.,Partridge, Lynda Z.,Learmonth, Michele P.,Ball, Hayden L.,Gibbons, William A.
p. 815 - 830
(2007/10/02)