615-76-9Relevant academic research and scientific papers
2-Hydroxyimino-6-aza-pyrimidine nucleosides: Synthesis, DFT calculations, and antiviral evaluations
Abou-Elkhair, Reham A. I.,Wasfy, Abdalla A.,Mao, Song,Du, Jinxi,Eladl, Sobhy,Metwally, Kamel,Hassan, Abdalla E. A.,Sheng, Jia
, p. 19650 - 19662 (2020/12/05)
The global public health concerns and economic impact caused by emerging outbreaks of RNA viruses call for the search for new direct acting antiviral agents. Herein, we describe the synthesis, DFT calculations, and antiviral evaluation of a series of novel 2-hydroxyimino-6-aza-pyrimidine ribonucleosides. DFT//B3LYP/6-311+G?? calculations of the tautomeric distributions of the 2-hydroxyimino nucleosides 7, 8, and 9 in aqueous environments indicate a predominance of the canonical 2-(E)-hydroxyimino structure, where the hydroxyl group points away from the sugar moiety. The conformer distributions of the latter geometrical isomers of 7, 8, and 9 support the formation of five membered rings via hydrogen bonding between the (E)-C2N-O-H moiety and N3-H of 7 and 8 and between (E)-C2N-O-H and N3 of 9, creating purine shaped nucleosides with the glycosidic linkage at the pyrimidine ring. The newly synthesized nucleosides were screened against an RNA viral panel, of which moderate antiviral activity was observed against Zika virus (ZIKV) and human respiratory syncytial virus (HRSV). 6-Aza-2-hydroxyimino-5-methyluridine derivative 18 showed activity against ZIKV (EC50 3.2 μM), while its peracetylated derivative 19 showed activity against HRSV (EC50 5.2 μM). The corresponding 4-thiono-2-hydroxyimino derivative 8 showed activity against HRSV (EC50 6.1 μM) and against ZIKA (EC50 2.4 μM). This study shows that the 6-aza-2-hydroxyimino-5-methyluracil derived nucleosides can be further optimized to provide potent antiviral agents. This journal is
Experimental and theoretical study on the regioselective synthesis and reaction of some bis- and poly(3-mercapto-1,2,4-triazin-5(4H)-one) derivatives
Diab, Hadeer M.,Hassan, Walid M.I.,Abdelhamid, Ismail A.,Elwahy, Ahmed H.M.
, p. 244 - 261 (2019/07/31)
The synthetic utility of 3-thioxo-1,2,4-triazin-5-ones 1 and 4-amino-3-mercapto-1,2,4-triazin-5(4H)-ones 2 as building blocks for novel bis- and poly(1,2,4-triazines) via alkylation with the corresponding bis- and poly(halo) compounds was investigated. Prediction of the site of alkylation has been confirmed using spectroscopic data. Theoretical calculation using hybrid density functional method wb97xd and 6-311++g(d,p) as basis set was implemented to investigate the reaction products energetics parameters. The atomic charges were calculated and discussed in details using three different methods. The transition state search were implemented to estimate the Gibbs free activation energy barrier of the reaction to emphasis the experimental results.
CERTAIN PROTEIN KINASE INHIBITORS
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Paragraph 00140; 00141, (2015/12/18)
Provided are compound of formula (I) as certain CDK4/6 inhibitors, pharmaceutical compositions thereof, and methods of use thereof.
Synthesis and evaluation of 6-Aza-2′-deoxyuridine monophosphate analogs as inhibitors of thymidylate synthases, and as substrates or inhibitors of thymidine monophosphate kinase in mycobacterium tuberculosis
Koegler, Martin,Busson, Roger,De Jonghe, Steven,Rozenski, Jef,Van Belle, Kristien,Louat, Thierry,Munier-Lehmann, Helne,Herdewijn, Piet
experimental part, p. 536 - 556 (2012/05/20)
A series of 5-substituted analogs of 6-aza-2′-deoxyuridine 5′-monophosphate, 6-aza-dUMP, has been synthesized and evaluated as potential inhibitors of the two mycobacterial thymidylate synthases (i.e., a flavin-dependent thymidylate synthase, ThyX, and a classical thymidylate synthase, ThyA). Replacement of C(6) of the natural substrate dUMP by a N-atom in 6-aza-dUMP 1a led to a derivative with weak ThyX inhibitory activity (33% inhibition at 50 μM). Introduction of alkyl and aryl groups at C(5) of 1a resulted in complete loss of inhibitory activity, whereas the attachment of a 3-(octanamido)prop-1-ynyl side chain in derivative 3 retained the weak level of mycobacterial ThyX inhibition (40% inhibition at 50 μM). None of the synthesized derivatives displayed any significant inhibitory activity against mycobacterial ThyA. The compounds have also been evaluated as potential inhibitors of mycobacterial thymidine monophosphate kinase (TMPKmt). None of the derivatives showed any significant TMPKmt inhibition. However, replacement of C(6) of the natural substrate (dTMP) by a N-atom furnished 6-aza-dTMP (1b), which still was recognized as a substrate by TMPKmt. Copyright
CERTAIN DIPEPTIDYL PEPTIDASE INHIBITORS
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Page/Page column 18, (2011/07/08)
Provided are certain dipeptidyl peptidase inhibitors, pharmaceutical compositions thereof, and methods of use therefor.
Deamination of some N-amino nitrogen heterocycles using Preyssler's anion
Heravi, Majid M.,Sadjadi, Sodeh,Hekmatshoar, Rahim,Oskooie, Hossein A.,Bamoharram, Fatemeh F.
, p. 107 - 110 (2008/09/20)
Some N-aminotriazines and -triazoles were treated with Preyssler's anion as catalyst in acetic acid to afford the corresponding deaminated triazines and triazoles. The reaction is suggested to proceed via formation of N-nitrosamines with subsequent N-NO b
Efficient dual catalytic enantioselective diethylzinc addition to the exocyclic C{double bond, long}N double bond of some 1,2,4-N-triazinylarylimines using polymer-supported chiral β-amino alcohols derived from norephedrine
El-Shehawy, Ashraf A.
, p. 5490 - 5500 (2008/01/07)
Chiral N,N-dialkylnorephedrines and their corresponding copolymers were evaluated as chiral ligands for the enantioselective diethylzinc addition to the exocyclic C{double bond, long}N double bond of some 4-arylideneamino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-ones 2a-f. The use of a dual catalytic system (amino alcohol/halosilane) in the titled asymmetric reaction was examined. The enantioselective ethylation reaction has been successfully carried out in the heterogeneous system even at low temperature. The corresponding 4-(1-arylpropyl)amino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-ones 4a-f were obtained in high yields with high enantioselectivities using chiral polymers (up to 91% ee), which are almost the same as those obtained from homogeneous analogues (up to 92% ee). The diethylzinc reagent neither opened the 1,2,4-triazinyl heterocyclic ring nor attacked the carbonyl or the thione groups of the 1,2,4-triazinyl heterocyclic ring and the addition reaction took place exclusively at the exocyclic electrophilic carbon atom yielding the C-ethylated products 4a-f. Reductive cleavage of the 1,2,4-triazinyl heterocyclic ring led smoothly to the corresponding primary aromatic amines 11a-f without significant loss of enantiomeric purity. A?suggestion about the possible transition state for the addition reaction is also presented.
Enantioselective diethylzinc addition to the exocyclic C{double bond, long}N double bond of some 4-arylideneamino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-one derivatives
El-Shehawy, Ashraf A.
, p. 2617 - 2624 (2007/10/03)
4-Arylideneamino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-ones 2a-f have been evaluated as substrates in the enantioselective diethylzinc addition reaction in the presence of (1S,2R)-N-alkyl-N-benzylnorephedrines 3a-d as chiral ligands. The utility of using a dual catalytic system (amino alcohol/halosilane) for the diethylzinc addition reaction has been also examined. The addition products 4-(1-arylpropyl)amino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-ones 4a-f were obtained in high yields and with enantiomeric excesses of up to 92%. The treatment of arylimines 2a-f with a diethylzinc reagent did not affect the hetero-ring opening although the C{double bond, long}N double bond of the lateral chain did undergo an addition reaction to yield the C-ethylated products 4a-f. The reductive cleavage of the 1,2,4-triazinyl heterocyclic ring from addition products 4a-f led smoothly to the corresponding free primary amines 5a-f without a significant loss of enantiomeric purity.
Stereocontrolled synthesis of functionalized cis-cyclopentapyrazolidines by 1,3-dipolar cycloaddition reactions of azomethine imines
Gergely, Joshua,Morgan, Jeremy B.,Overman, Larry E.
, p. 9144 - 9152 (2007/10/03)
(Chemical Equation Presented) The reaction of alkene-tethered α-ketocarboxylic acid derivatives with monosubstituted hydrazines allows highly substituted cis-cyclopentapyrazolidine ring systems 4 to be constructed rapidly. Successful cyclocondensations are realized under thermal reaction conditions; in some cases, protic or Lewis acids accelerate these reactions. α-Methoxy-α,β-unsaturated esters are suitable alkene components, as are alkenes having either electron-withdrawing or electron-donating substituents at the terminal alkene carbon. α-Ketoesters, α-ketoamides, and α-ketothioesters can be employed. Various hydrazines substituted with N-acyl, N-carboalkoxy, or N-carbamothioyl protecting groups are tolerated in these transformations. The rate of intramolecular cycloaddition is found to reflect not only the reactivity and equilibrium concentration of the azomethine imine intermediate, but, also in some cases, the rate at which hydrazone stereoisomers interconvert under the reaction conditions.
Synthesis of some nitrogen heterocycles under microwave irradiation in solventless system
Oskooie, Hossein A.,Heravi, Majid M.,Nami, Navvabeh,Nazari, Azadeh
, p. 101 - 104 (2007/10/03)
A Superior and fast method of synthesis of some nitrogen heterocycles under microwave irradiation in solventless system is described.
