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Murray N Robertson - One of the best experts on this subject based on the ideXlab platform.

  • synthesis dna pk inhibition anti platelet activity studies of 2 n substituted 3 aminopyridine substituted 1 3 benzoxazines and dna pk and pi3k inhibition homology modelling studies of 2 morpholino 7 8 di and 8 substituted 1 3 benzoxazines
    European Journal of Medicinal Chemistry, 2012
    Co-Authors: Saleh Ihmaid, Jasim M A Alrawi, Christopher Bradley, Michael J Angove, Murray N Robertson
    Abstract:

    Abstract A number of new 2-(pyridin-3-ylamino)-4H-(substituted) benz[e]-1,3-oxazin-4-ones were synthesized 10a–g. These were then reacted with the hydro-halogen salt of 2, 3 and 4-(halo-methyl) pyridine in the presence of Cs2CO3 to give eighteen new 2-(N-substituted (pyridin-3-ylmethyl) amino)-substituted-1,3-benzoxazines (compounds 11a–i, 13a–c, and 15a–f). X-ray crystallography was used to confirm that the 2-N-substituted structures 11 and 13 were formed rather than the 3-N-substitution analogues 12 and 14. Eleven of the new compounds were tested for their effect on collagen induced platelet aggregation and it was found that the most active inhibitory compound was 8-methyl-2-(pyridin-3-yl(pyridin-3-ylmethyl)amino)-7-(pyridin-3-ylmEthoxy)-4H-benz[e]-1,3-oxazin-4-one 15e with an IC50 of 10 ± 2 μM. DNA-dependent protein kinase (DNA-PK) inhibition data for 12 previously prepared 2-morpholino substituted-1,3-benzoxazines (compounds 19–31) were measured and showed high to moderate activity where the most active compound was compound 27 with an IC50 of 0.28 μM. Furthermore DNA-PK inhibition data for six newly prepared 2-(N-substituted (pyridin-3-ylmethyl) amino)-substituted-1,3-benzoxazines (compounds 11b, 13a–b, 15a–b and 15e) and 8-methyl-7-(pyridin-3-ylmEthoxy)-3-(pyridin-3-ylmethyl)-2H-benz[e]-1,3-oxazin-2,4(3H)-dione 17d were measured and moderate to low inhibitory activity was observed, with the most active of the compounds in this series being 8-methyl-2-(pyridin-3-yl(pyridin-3-ylmethyl)amino)-7-(pyridin-3-ylmEthoxy)-4H-benz[e]-1,3-oxazin-4-one 15e with an IC50 of 2.5 μM. PI3K inhibition studies revealed that compound 27 is highly potent (IC50 for PI3Kα = 0.13 μM, PI3Kβ = 0.14 μM, PI3Kγ = 0.72 μM, PI3Kδ = 2.02 μM). Compound 22 with 7-[2-(4-methylpiperazin-1-yl)Ethoxy] Group shows greater inhibition of DNA-PK over PI3K. Docking of some 2-morpholino-substituted-1,3-benzoxazine compounds 19–31 within the binding pocket and structure–activity relationship s (SAR) analyses were performed with results agreeing well with observed activities.

Zekeriya Bıyıklıoğlu - One of the best experts on this subject based on the ideXlab platform.

Ernst Kenndler - One of the best experts on this subject based on the ideXlab platform.

  • Separation of Ethoxylated bisphenol A dimethacrylates in dental composite after derivatisation to ionisable amines by capillary zone electrophoresis.
    Journal of chromatography. A, 2004
    Co-Authors: Alessandro Musenga, Andreas Schedle, Uwe M. Demelbauer, Leopold Kremser, Maria Augusta Raggi, Ernst Kenndler
    Abstract:

    Bisphenol A Ethoxylate dimethacrylates (Bis-EMA) are transformed into ionisable amines by derivatisation in order to make the analytes applicable to capillary electrophoresis. For this goal, piperidine was added onto the C=C double bond of the alpha,beta-unsaturated ester Group forming a tertiary amine with pKa values between 9 and 10. Formation of the derivatives was confirmed by electrospray ionisation MS. Commercial Bis-EMA is a mixture of homologues with different number of Ethoxy Groups; it is characterised by the average number of the Ethoxy Groups in the chains. These homologues were resolved by capillary zone electrophoresis at pH 4. It is shown for the product with an average of four Ethoxy Groups per Bis-EMA molecule that about seven homologues can be baseline separated when differing by only one Ethoxy Group. For Bis-EMA with 30 Ethoxy Groups in average, about 23 homologues could be differentiated. The high resolution power of capillary zone electrophoresis enables characterisation of commercial dental composite material concerning the Bis-EMA constituents.

  • Separation of Ethoxylated bisphenol A dimethacrylates in dental composite after derivatisation to ionisable amines by capillary zone electrophoresis
    Journal of Chromatography A, 2004
    Co-Authors: Alessandro Musenga, Andreas Schedle, Uwe M. Demelbauer, Leopold Kremser, Maria Augusta Raggi, Ernst Kenndler
    Abstract:

    Abstract Bisphenol A Ethoxylate dimethacrylates (Bis-EMA) are transformed into ionisable amines by derivatisation in order to make the analytes applicable to capillary electrophoresis. For this goal, piperidine was added onto the CC double bond of the α,β-unsaturated ester Group forming a tertiary amine with pKa values between 9 and 10. Formation of the derivatives was confirmed by electrospray ionisation MS. Commercial Bis-EMA is a mixture of homologues with different number of Ethoxy Groups; it is characterised by the average number of the Ethoxy Groups in the chains. These homologues were resolved by capillary zone electrophoresis at pH 4. It is shown for the product with an average of four Ethoxy Groups per Bis-EMA molecule that about seven homologues can be baseline separated when differing by only one Ethoxy Group. For Bis-EMA with 30 Ethoxy Groups in average, about 23 homologues could be differentiated. The high resolution power of capillary zone electrophoresis enables characterisation of commercial dental composite material concerning the Bis-EMA constituents.

Saleh Ihmaid - One of the best experts on this subject based on the ideXlab platform.

  • synthesis dna pk inhibition anti platelet activity studies of 2 n substituted 3 aminopyridine substituted 1 3 benzoxazines and dna pk and pi3k inhibition homology modelling studies of 2 morpholino 7 8 di and 8 substituted 1 3 benzoxazines
    European Journal of Medicinal Chemistry, 2012
    Co-Authors: Saleh Ihmaid, Jasim M A Alrawi, Christopher Bradley, Michael J Angove, Murray N Robertson
    Abstract:

    Abstract A number of new 2-(pyridin-3-ylamino)-4H-(substituted) benz[e]-1,3-oxazin-4-ones were synthesized 10a–g. These were then reacted with the hydro-halogen salt of 2, 3 and 4-(halo-methyl) pyridine in the presence of Cs2CO3 to give eighteen new 2-(N-substituted (pyridin-3-ylmethyl) amino)-substituted-1,3-benzoxazines (compounds 11a–i, 13a–c, and 15a–f). X-ray crystallography was used to confirm that the 2-N-substituted structures 11 and 13 were formed rather than the 3-N-substitution analogues 12 and 14. Eleven of the new compounds were tested for their effect on collagen induced platelet aggregation and it was found that the most active inhibitory compound was 8-methyl-2-(pyridin-3-yl(pyridin-3-ylmethyl)amino)-7-(pyridin-3-ylmEthoxy)-4H-benz[e]-1,3-oxazin-4-one 15e with an IC50 of 10 ± 2 μM. DNA-dependent protein kinase (DNA-PK) inhibition data for 12 previously prepared 2-morpholino substituted-1,3-benzoxazines (compounds 19–31) were measured and showed high to moderate activity where the most active compound was compound 27 with an IC50 of 0.28 μM. Furthermore DNA-PK inhibition data for six newly prepared 2-(N-substituted (pyridin-3-ylmethyl) amino)-substituted-1,3-benzoxazines (compounds 11b, 13a–b, 15a–b and 15e) and 8-methyl-7-(pyridin-3-ylmEthoxy)-3-(pyridin-3-ylmethyl)-2H-benz[e]-1,3-oxazin-2,4(3H)-dione 17d were measured and moderate to low inhibitory activity was observed, with the most active of the compounds in this series being 8-methyl-2-(pyridin-3-yl(pyridin-3-ylmethyl)amino)-7-(pyridin-3-ylmEthoxy)-4H-benz[e]-1,3-oxazin-4-one 15e with an IC50 of 2.5 μM. PI3K inhibition studies revealed that compound 27 is highly potent (IC50 for PI3Kα = 0.13 μM, PI3Kβ = 0.14 μM, PI3Kγ = 0.72 μM, PI3Kδ = 2.02 μM). Compound 22 with 7-[2-(4-methylpiperazin-1-yl)Ethoxy] Group shows greater inhibition of DNA-PK over PI3K. Docking of some 2-morpholino-substituted-1,3-benzoxazine compounds 19–31 within the binding pocket and structure–activity relationship s (SAR) analyses were performed with results agreeing well with observed activities.

Kenneth Gable - One of the best experts on this subject based on the ideXlab platform.

  • Activation and inhibition of the sarcoplasmic reticulum Ca^2+ channel by the polycationic dyes Hoechst 33342 and Hoechst 33258
    The Journal of Membrane Biology, 1993
    Co-Authors: Troy J. Beeler, Kenneth Gable
    Abstract:

    The polycationic dyes, Hoechst 33342 (Bisbenzimide,2′-(4-Ethoxyphenyl)-5-(4-methyl-1-piperazinyl) 2,5′-bi 1H benzimidazole) and Hoechst 33258 (Bisbenzimide,2′-(4-hydroxyphenyl) 5-(4-methyl-1-piperazinyl)-2,5′-bi-1H-benzimidazole) alter the activity of the sarcoplasmic reticulum Ca^2+ channel. Although they act competitively, Hoechst 33342 decreases, while Hoechst 33258 increases, the rate of channel-mediated Ca^2+ efflux from junctional sarcoplasmic reticulum vesicles. Unlike other cationic sarcoplasmic reticulum Ca^2+ channel antagonists, Hoechst 33342 blocks the ryanodine-activated Ca^2+ channel. Both Hoechst 33342 and Hoechst 33258 inhibit the channel incorporated into the planar lipid bilayer. Since the only structural difference between the two dyes is that the agonist Hoechst 33258 has a hydroxy Group where the antagonist Hoechst 33342 has an Ethoxy Group, it is possible that the more hydrophobic, bulky Ethoxy Group blocks Ca^2+ movement through the channel, whereas the hydroxy Group only reduces the rate of Ca^2+ movement. The opinions or assertions contained herein are private ones of the author ad are not to beconstrued as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences.

  • Activation and inhibition of the sarcoplasmic reticulum Ca2+ channel by the polycationic dyes Hoechst 33342 and Hoechst 33258.
    The Journal of membrane biology, 1993
    Co-Authors: Troy Beeler, Kenneth Gable
    Abstract:

    The polycationic dyes, Hoechst 33342 (Bisbenzimide,2′-(4-Ethoxyphenyl)-5-(4-methyl-1-piperazinyl) 2,5′-bi 1H benzimidazole) and Hoechst 33258 (Bisbenzimide,2′-(4-hydroxyphenyl) 5-(4-methyl-1-piperazinyl)-2,5′-bi-1H-benzimidazole) alter the activity of the sarcoplasmic reticulum Ca2+ channel. Although they act competitively, Hoechst 33342 decreases, while Hoechst 33258 increases, the rate of channel-mediated Ca2+ efflux from junctional sarcoplasmic reticulum vesicles. Unlike other cationic sarcoplasmic reticulum Ca2+ channel antagonists, Hoechst 33342 blocks the ryanodine-activated Ca2+ channel. Both Hoechst 33342 and Hoechst 33258 inhibit the channel incorporated into the planar lipid bilayer. Since the only structural difference between the two dyes is that the agonist Hoechst 33258 has a hydroxy Group where the antagonist Hoechst 33342 has an Ethoxy Group, it is possible that the more hydrophobic, bulky Ethoxy Group blocks Ca2+ movement through the channel, whereas the hydroxy Group only reduces the rate of Ca2+ movement.