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Your search keyword '"Silver, LL"' showing total 3 results
Start Over Author "Silver, LL" Publisher american chemical society
3 results on '"Silver, LL"'

1. Setting Our Sights on Infectious Diseases

Author

De Rycker, M, Horn, D, Aldridge, B, Amewu, RK, Barry, CE, Buckner, FS, Cook, S, Ferguson, MAJ, Gobeau, N, Herrmann, J, Herding, P, Hope, W, Keiser, J, Lafuente-Monasterio, MJ, Leeson, PD, Leroy, D, Manjunatha, UH, McCarthy, J, Miles, TJ, Mizrahi, V, Moshynets, O, Niles, J, Overington, JP, Pottage, J, Rao, SPS, Read, KD, Ribeiro, I, Silver, LL, Southern, J, Spangenberg, T, Sundar, S, Taylor, C, Van Voorhis, W, White, NJ, Wyllie, S, Wyatt, PG, Gilbert, IH, De Rycker, M, Horn, D, Aldridge, B, Amewu, RK, Barry, CE, Buckner, FS, Cook, S, Ferguson, MAJ, Gobeau, N, Herrmann, J, Herding, P, Hope, W, Keiser, J, Lafuente-Monasterio, MJ, Leeson, PD, Leroy, D, Manjunatha, UH, McCarthy, J, Miles, TJ, Mizrahi, V, Moshynets, O, Niles, J, Overington, JP, Pottage, J, Rao, SPS, Read, KD, Ribeiro, I, Silver, LL, Southern, J, Spangenberg, T, Sundar, S, Taylor, C, Van Voorhis, W, White, NJ, Wyllie, S, Wyatt, PG, and Gilbert, IH

Abstract

In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learnings.

Published
2020

3. Novel pyrazolo[3,4-d]pyrimidine-based inhibitors of Staphlococcus aureus DNA polymerase III: design, synthesis, and biological evaluation.

Author

Ali A, Taylor GE, Ellsworth K, Harris G, Painter R, Silver LL, and Young K

Subjects
Aniline Compounds chemical synthesis, Aniline Compounds chemistry, Aniline Compounds pharmacology, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Bacillus subtilis drug effects, Drug Design, Enterococcus faecium drug effects, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Microbial Sensitivity Tests, Pyrazoles chemistry, Pyrazoles pharmacology, Pyrimidines chemistry, Pyrimidines pharmacology, Staphylococcus aureus drug effects, Streptococcus pneumoniae drug effects, Structure-Activity Relationship, Anti-Bacterial Agents chemical synthesis, DNA Polymerase III antagonists & inhibitors, Enzyme Inhibitors chemical synthesis, Pyrazoles chemical synthesis, Pyrimidines chemical synthesis, Staphylococcus aureus enzymology
Abstract

6-Anilinopyrazolo[3,4-d]pyrimidin-4-ones are novel dGTP analogues that inhibit the replication-specific enzyme DNA polymerase III (DNA pol III) of Staphlococcus aureus and other Gram-positive (Gr+) bacteria. To enhance the potential of these inhibitors as antimicrobial agents, a structure-activity relationship was developed involving substitutions at the 2, 4, and pyrazolo NH positions. All of the new inhibitors were tested for their ability to inhibit S. aureus DNA pol III and the growth of several other Gr+ bacteria in culture. 2-Anilino groups with small hydrophobic groups in the meta or para position enhanced both antipolymerase and antimicrobial activity. 2-Benzyl-substituted inhibitors were substantially less active. Substitution in the 4-position by oxygen gave the optimal activity, whereas substitution at the pyrazolo NH was not tolerated. These pyrazolo[3,4-d]pyrimidine derivatives represent a novel class of antimicrobials with promising activities against Gr+ bacteria.

Published
2003
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