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Your search keyword '"McLean, Neville J."' showing total 13 results
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13 results on '"McLean, Neville J."'

2. Optimization of Potent, Efficacious, Selective and Blood–Brain Barrier Penetrating Inhibitors Targeting EGFR Exon20 Insertion Mutations

Author

Thomson, Clare, Braybrooke, Erin, Colclough, Nicola, Davies, Nichola L., Floc’h, Nicolas, Greenwood, Ryan, Guérot, Carine, Hargreaves, David, Johnstrom, Peter, Khurana, Puneet, Kostomiris, Demetrios H., Li, Songlei, Lister, Andrew, Lorthioir, Olivier, Martin, Scott, McCoull, William, McLean, Neville J., McWilliams, Lisa, Orme, Jonathan P., Packer, Martin J., Pearson, Stuart, Swaih, Aisha M., Tentarelli, Sharon, Tucker, Michael J., Ward, Richard A., Wilkinson, Stephen, Winlow, Poppy, and Wood, Isabel L.

Abstract

Herein, we report the optimization of a series of epidermal growth factor receptor (EGFR) Exon20 insertion (Ex20Ins) inhibitors using structure-based drug design (SBDD), leading to the discovery of compound 28, a potent and wild type selective molecule, which demonstrates efficacy in multiple EGFR Ex20Ins xenograft models and blood–brain barrier penetration in preclinical species. Building on our earlier discovery of an in vivoprobe, SBDD was used to design a novel bicyclic core with a lower molecular weight to facilitate blood–brain barrier penetration. Further optimization including strategic linker replacement and diversification of the ring system interacting with the c-helix enabled photolytic and metabolic stability improvements. Together with refinement of molecular properties important for achieving high brain exposure, including molecular weight, H-bonding, and polarity, 28was identified.

Published
2024
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6. Discovery of thiazolobenzoxepin PI3-kinase inhibitors that spare the PI3-kinase β isoform

Author

Staben, Steven T., Ndubaku, Chudi, Blaquiere, Nicole, Belvin, Marcia, Bull, Richard J., Dudley, Danette, Edgar, Kyle, Gray, Daniel, Heald, Robert, Heffron, Timothy P., Jones, Graham E., Jones, Mark, Kolesnikov, Aleks, Lee, Leslie, Lesnick, John, Lewis, Cristina, Murray, Jeremy, McLean, Neville J., Nonomiya, Jim, Olivero, Alan G., Ord, Rachel, Pang, Jodie, Price, Stephen, Prior, Wei Wei, Rouge, Lionel, Salphati, Laurent, Sampath, Deepak, Wallin, Jeff, Wang, Lan, Wei, BinQing, Weismann, Christian, and Wu, Ping

Published
2013
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12. Syntheses of 13C2-labelled 11Z-retinals

Author

McLean, Neville J., Gansmuller, Axel, Concistre, Maria, Brown, Lynda J., Levitt, Malcom H., and Brown, Richard C.D.

Subjects
*SOLID state chemistry, *NUCLEAR magnetic resonance, *RHODOPSIN, *INTERMEDIATES (Chemistry), *CARBON isotopes, *HECK reaction
Abstract

Abstract: To enable solid-state NMR investigations of the rhodopsin chromophore and its photointermediates, a series of 11Z-retinal isotopomers have been synthesised containing pairs of adjacent 13C labels at C9/C10, C10/C11 or C11/C12, respectively. The C9 labelled carbon atom was introduced through the Heck reaction of a 13C-labelled Weinreb acrylamide derivative, and the label at the C12 position derived from a 13C-containing ethoxy Bestmann–Ohira reagent. The 13C labels at C10 and C11 were introduced through the reaction of β-ionone with labelled triethyl phosphonoacetate. [Copyright &y& Elsevier]

Published
2011
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13. Stereocontrolled synthesis of (-)-galanthamine.

Author

Satcharoen V, McLean NJ, Kemp SC, Camp NP, and Brown RC

Subjects
Cyclization, Galantamine chemistry, Molecular Structure, Stereoisomerism, Galantamine chemical synthesis
Abstract

An enantioselective synthesis of (-)-galanthamine has been realized in 11 linear steps starting from isovanillin. A Mitsunobu aryl ether forming reaction was used to assemble the galanthamine backbone, which was stitched together using enyne ring-closing metathesis, Heck, and N-alkylation reactions affording the tetracyclic ring system. Control of relative and absolute stereochemistry was derived from an easily accessible enantiomerically enriched propargylic alcohol 13.

Published
2007
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