122 results found
Evans LE, Krishna A, Ma Y, et al., 2019, Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug., J Med Chem, Vol: 62, Pages: 4411-4425
Expression of β-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to β-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a β-lactamase-cleavable motif. The prodrug is only bactericidal after activation by β-lactamase. Bactericidal activity comparable to ciprofloxacin is demonstrated against clinically relevant E. coli isolates expressing diverse β-lactamases; bactericidal activity was not observed in strains without β-lactamase. These findings demonstrate that it is possible to exploit antibiotic resistance to selectively target β-lactamase-producing bacteria using our prodrug approach, without adversely affecting bacteria that do not produce β-lactamase. This paves the way for selective targeting of drug-resistant pathogens without disrupting or selecting for resistance within the microbiota, reducing the rate of secondary infections and subsequent antibiotic use.
Craven GB, Affron DP, Raymond PN, et al., 2019, Vinyl sulfonamide synthesis for irreversible tethering via a novel alpha-selenoether protection strategy, MEDCHEMCOMM, Vol: 10, Pages: 158-163, ISSN: 2040-2503
Craven GB, Affron DP, Allen CE, et al., 2018, High-Throughput Kinetic Analysis for Target-Directed Covalent Ligand Discovery, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 57, Pages: 5257-5261, ISSN: 1433-7851
Mann D, Armstrong A, Craven G, et al., 2018, (WO2018033753) ASSAY, PCT/GB2017/052456
The present invention relates to a method of measuring the rate of reaction between a target molecule and a ligand candidate, ligands of interest identified according to this method and drugs developed from such ligands. The present invention also relates to a method of measuring the rate of reaction between a thiol and a molecule capable of reacting with said thiol.
Grant E, Pan Y, Richardson J, et al., 2018, Multi-Objective Computer-Aided Solvent Design for Selectivity and Rate in Reactions, Computer Aided Chemical Engineering, Pages: 2437-2442
© 2018 Elsevier B.V. A hybrid empirical computer-aided methodology to design the solvent for a reaction, incorporating both selectivity and rate, is presented. A small initial set of diverse solvents is used, for which experimental, in situ kinetic data are obtained. A surrogate model is utilized to correlate the reaction kinetics with solvent properties and a computer-aided molecular design (CAMD) multi-objective optimization problem is then formulated to identify solvents with improved performance compared with the initial solvent set. This methodology is applied to an S N Ar reaction of 2,4-difluoroacetophenone with pyrrolidine, which demonstrates an interesting effect of solvent on both the selectivity of the ortho-:para-substitution ratio and the overall rate of the reaction. A set of Pareto optimal solutions is identified, highlighting the trade-off between reaction rate and selectivity.
Armstrong A, Ces O, Compte RV, 2017, All aboard for chemistry, CHEMISTRY & INDUSTRY, Vol: 81, Pages: 14-15, ISSN: 0009-3068
Sung S, Sale D, Braddock DC, et al., 2016, Mechanistic Studies on the Copper-Catalyzed N-Arylation of Alkylamines Promoted by Organic Soluble Ionic Bases, ACS CATALYSIS, Vol: 6, Pages: 3965-3974, ISSN: 2155-5435
Alguel Y, Amillis S, Leung J, et al., 2016, Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723
Bures J, Armstrong A, Blackmond DG, 2016, Explaining Anomalies in Enamine Catalysis: "Downstream Species" as a New Paradigm for Stereocontrol, ACCOUNTS OF CHEMICAL RESEARCH, Vol: 49, Pages: 214-222, ISSN: 0001-4842
Armstrong A, Pullin RDC, Scutt JN, 2016, Tertiary Amine Promoted Aziridination: Preparation of NH-Aziridines from Aliphatic ,-Unsaturated Ketones, SYNLETT, Vol: 27, Pages: 151-155, ISSN: 0936-5214
Sung S, Braddock DC, Armstrong A, et al., 2015, Synthesis, Characterisation and Reactivity of Copper(I) Amide Complexes and Studies on Their Role in the Modified Ullmann Amination Reaction, CHEMISTRY-A EUROPEAN JOURNAL, Vol: 21, Pages: 7179-7192, ISSN: 0947-6539
Allen CE, Curran PR, Brearley AS, et al., 2015, Efficient and Facile Synthesis of Acrylamide Libraries for Protein-Guided Tethering, ORGANIC LETTERS, Vol: 17, Pages: 458-460, ISSN: 1523-7060
Bures J, Dingwall P, Armstrong A, et al., 2014, Rationalization of an Unusual Solvent-Induced Inversion of Enantio-meric Excess in Organocatalytic Selenylation of Aldehydes, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 53, Pages: 8700-8704, ISSN: 1433-7851
Armstrong A, Emmerson DPG, Milner HJ, et al., 2014, [2,3]-Sigmatropic Rearrangement of Allylic Selenimides: Strategy for the Synthesis of Peptides, Peptidomimetics, and N-Aryl Vinyl Glycines, JOURNAL OF ORGANIC CHEMISTRY, Vol: 79, Pages: 3895-3907, ISSN: 0022-3263
Armstrong A, Pullin RDC, Jenner CR, et al., 2014, Tertiary amine-promoted enone aziridination: investigations into factors influencing enantioselective induction, TETRAHEDRON-ASYMMETRY, Vol: 25, Pages: 74-86, ISSN: 0957-4166
Armstrong A, Boto RA, Dingwall P, et al., 2014, The Houk-List transition states for organocatalytic mechanisms revisited, CHEMICAL SCIENCE, Vol: 5, Pages: 2057-2071, ISSN: 2041-6520
Armstrong A, Braddock DC, Jones AX, et al., 2013, Catalytic asymmetric bromolactonization reactions using (DHQD)(2)PHAL-benzoic acid combinations, TETRAHEDRON LETTERS, Vol: 54, Pages: 7004-7008, ISSN: 0040-4039
Struebing H, Ganase Z, Karamertzanis PG, et al., 2013, Computer-aided molecular design of solvents for accelerated reaction kinetics, NATURE CHEMISTRY, Vol: 5, Pages: 952-957, ISSN: 1755-4330
Collins JC, Armstrong A, Chapman KL, et al., 2013, Prospective use of molecular field points in ligand-based virtual screening: efficient identification of new reversible Cdc25 inhibitors, MEDCHEMCOMM, Vol: 4, Pages: 1148-1155, ISSN: 2040-2503
Bures J, Armstrong A, Blackmond DG, 2013, The interplay of thermodynamics and kinetics in dictating organocatalytic reactivity and selectivity, PURE AND APPLIED CHEMISTRY, Vol: 85, Pages: 1919-1934, ISSN: 0033-4545
Nonoo RH, Armstrong A, Mann DJ, 2012, Kinetic Template-Guided Tethering of Fragments, CHEMMEDCHEM, Vol: 7, Pages: 2082-2086, ISSN: 1860-7179
Armstrong A, Ferguson A, 2012, Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines, BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, Vol: 8, Pages: 1747-1752, ISSN: 1860-5397
Bures J, Armstrong A, Blackmond DG, 2012, Curtin-Hammett Paradigm for Stereocontrol in Organocatalysis by Diarylprolinol Ether Catalysts, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 134, Pages: 6741-6750, ISSN: 0002-7863
Bures J, Armstrong A, Blackmond DG, 2012, Kinetic correlation between aldehyde/enamine stereoisomers in reactions between aldehydes with alpha-stereocenters and chiral pyrrolidine-based catalysts, CHEMICAL SCIENCE, Vol: 3, Pages: 1273-1277, ISSN: 2041-6520
Hein JE, Bures J, Lam Y-H, et al., 2011, Enamine Carboxylates as Stereodetermining Intermediates in Prolinate Catalysis, ORGANIC LETTERS, Vol: 13, Pages: 5644-5647, ISSN: 1523-7060
Armstrong A, Deacon N, Donald C, 2011, Enantioselective Synthesis of alpha-Aminophosphonates via Organocatalytic Sulfenylation and [2,3]-Sigmatropic Sulfimide Rearrangement, SYNLETT, Pages: 2347-2350, ISSN: 0936-5214
Hein JE, Armstrong A, Blackmond DG, 2011, Kinetic profiling of prolinate-catalyzed α-amination of aldehydes., Org Lett, Vol: 13, Pages: 4300-4303
Deconvolution of the role of off-cycle species from the desired catalytic cycle leads to an optimized protocol for the prolinate-catalyzed amination of aldehydes. The scope of complex reaction networks will be greatly broadened by understanding ancillary rate processes that influence the productive catalytic pathway.
Hein JE, Armstrong A, Blackmond DG, 2011, Kinetic Profiling of Prolinate-Catalyzed alpha-Amination of Aldehydes, ORGANIC LETTERS, Vol: 13, Pages: 4300-4303, ISSN: 1523-7060
Bures J, Armstrong A, Blackmond DG, 2011, Mechanistic Rationalization of Organocatalyzed Conjugate Addition of Linear Aldehydes to Nitro-olefins, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 133, Pages: 8822-8825, ISSN: 0002-7863
Armstrong A, Emmerson DPG, 2011, Enantioselective Synthesis of alpha-Alkyl, alpha-Vinyl Amino Acids via [2,3]-Sigmatropic Rearrangement of Selenimides, ORGANIC LETTERS, Vol: 13, Pages: 1040-1043, ISSN: 1523-7060
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.