Search

Your search keyword '"Andrew Eatherton"' showing total 6 results
Start Over Author "Andrew Eatherton"
6 results on '"Andrew Eatherton"'

1. Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRASG12C

Author

Jason G. Kettle, Sharan K. Bagal, Sue Bickerton, Michael S. Bodnarchuk, Scott Boyd, Jason Breed, Rodrigo J. Carbajo, Doyle J. Cassar, Atanu Chakraborty, Sabina Cosulich, Iain Cumming, Michael Davies, Nichola L. Davies, Andrew Eatherton, Laura Evans, Lyman Feron, Shaun Fillery, Emma S. Gleave, Frederick W. Goldberg, Lyndsey Hanson, Stephanie Harlfinger, Martin Howard, Rachel Howells, Anne Jackson, Paul Kemmitt, Gillian Lamont, Scott Lamont, Hilary J. Lewis, Libin Liu, Michael J. Niedbala, Christopher Phillips, Radek Polanski, Piotr Raubo, Graeme Robb, David M. Robinson, Sarah Ross, Matthew G. Sanders, Michael Tonge, Rebecca Whiteley, Stephen Wilkinson, Junsheng Yang, and Wenman Zhang

Subjects
Drug Discovery, Molecular Medicine
Published
2022

2. Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRAS

Author

Jason G, Kettle, Sharan K, Bagal, Sue, Bickerton, Michael S, Bodnarchuk, Scott, Boyd, Jason, Breed, Rodrigo J, Carbajo, Doyle J, Cassar, Atanu, Chakraborty, Sabina, Cosulich, Iain, Cumming, Michael, Davies, Nichola L, Davies, Andrew, Eatherton, Laura, Evans, Lyman, Feron, Shaun, Fillery, Emma S, Gleave, Frederick W, Goldberg, Lyndsey, Hanson, Stephanie, Harlfinger, Martin, Howard, Rachel, Howells, Anne, Jackson, Paul, Kemmitt, Gillian, Lamont, Scott, Lamont, Hilary J, Lewis, Libin, Liu, Michael J, Niedbala, Christopher, Phillips, Radek, Polanski, Piotr, Raubo, Graeme, Robb, David M, Robinson, Sarah, Ross, Matthew G, Sanders, Michael, Tonge, Rebecca, Whiteley, Stephen, Wilkinson, Junsheng, Yang, and Wenman, Zhang

Subjects
Proto-Oncogene Proteins p21(ras), Structure-Activity Relationship, Lung Neoplasms, Drug Design, Mutation, Quinazolines, Humans, Antineoplastic Agents
Abstract

KRAS is an archetypal high-value intractable oncology drug target. The glycine to cysteine mutation at codon 12 represents an Achilles heel that has now rendered this important GTPase druggable. Herein, we report our structure-based drug design approach that led to the identification of

Published
2022

3. Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRAS

Author

Jason G, Kettle, Sharan K, Bagal, Sue, Bickerton, Michael S, Bodnarchuk, Jason, Breed, Rodrigo J, Carbajo, Doyle J, Cassar, Atanu, Chakraborty, Sabina, Cosulich, Iain, Cumming, Michael, Davies, Andrew, Eatherton, Laura, Evans, Lyman, Feron, Shaun, Fillery, Emma S, Gleave, Frederick W, Goldberg, Stephanie, Harlfinger, Lyndsey, Hanson, Martin, Howard, Rachel, Howells, Anne, Jackson, Paul, Kemmitt, Jennifer K, Kingston, Scott, Lamont, Hilary J, Lewis, Songlei, Li, Libin, Liu, Derek, Ogg, Christopher, Phillips, Radek, Polanski, Graeme, Robb, David, Robinson, Sarah, Ross, James M, Smith, Michael, Tonge, Rebecca, Whiteley, Junsheng, Yang, Longfei, Zhang, and Xiliang, Zhao

Subjects
Male, Molecular Conformation, Mice, Nude, Antineoplastic Agents, Quinolones, Xenograft Model Antitumor Assays, Piperazines, Proto-Oncogene Proteins p21(ras), Structure-Activity Relationship, Allosteric Regulation, Cell Line, Tumor, Drug Design, Neoplasms, Mutation, Quinazolines, Animals, Humans, Caco-2 Cells, Rats, Wistar
Abstract

Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRAS

Published
2020

4. HIV Protease Inhibitors Part 2: [3+2] Cycloaddition, Isomerization; and Ring Expansion en route to 4,5-Substituted Cyclohexenones

Author

Irfan Kahn, Andrew Eatherton, Christopher S. Frampton, Emmanuel Hubert Demont, and Sally Redshaw

Subjects
chemistry.chemical_classification, Ketone, Chemistry, Stereochemistry, Organic Chemistry, Cyclohexanone, Ring (chemistry), Cycloaddition, chemistry.chemical_compound, Cyclohexenone, Indinavir, medicine, Cyclopentene, Isomerization, medicine.drug
Abstract

4,5-Substituted cyclohexanone 10 and its derivatives are carbocyclic analogues of Indinavir 3 and are expected to have antiviral activity. Early attempts to obtain these compounds via a diastereoselective [3+2] cycloaddition between 19 and 14 failed due to the sensitivity of the cycloadduct 24. It proved possible to obtain 30 from the α,β-unsaturated ester 27: [3+2] cycloaddition, isomerization, and ring expansion provided α,β-unsaturated ketone 31 from ester 26 in good yields. Further transformations of 31 gave the hydroxyethylamino inhibitor analogues of Indinavir 3.

Published
2004

5. HIV Protease Inhibitor Part 1: Use of Evans’ Oxazolidinone in Intermolecular Diels-Alder Reaction en route to 3,4-Substituted Cyclohexanones

Author

Andrew Eatherton, William Watson, Jenny C. Gilbert, Emmanuel Hubert Demont, Sally Redshaw, Peter Crackett, Christopher S. Frampton, and Irfan Kahn

Subjects
chemistry.chemical_classification, chemistry.chemical_compound, Diene, chemistry, Cyclohexane, Stereochemistry, Organic Chemistry, Intermolecular force, HIV Protease Inhibitor, Cyclohexanone, Aldehyde, Lewis acid catalysis, Diels–Alder reaction
Abstract

α,β-Unsaturated chiral oxazolidinone 10 can be smoothly obtained from the corresponding aldehyde 14 under Masamune-Roush conditions. Oxazolidinone 10 reacts diastereoselectively with diene 14 under lewis acid catalysis which allows the synthesis of 3,4-substituted cyclohexanone 16 and its derivatives 20, 21, and 22 in good overall yields from ester 4. These compounds can be converted to the corresponding hydroxyethylamine derivatives, analogues of Saquinavir 1, which are known to have antiviral activity.

Published
2004

6. Pyridazine-derived γ-secretase modulators

Author

Zehong Wan, Adrian Hall, Yun Jin, Jia-Ning Xiang, Eric Yang, Andrew Eatherton, Beverley Smith, Guang Yang, Haihua Yu, Ju Wang, Liang Ye, Lit-Fui Lau, Ting Yang, William Mitchell, Wei Cai, Xiaomin Zhang, Yingxia Sang, Yonghui Wang, Zhaolong Tong, Ziqiang Cheng, Ishrut Hussain, John D. Elliott, and Yasuji Matsuoka

Subjects
Amyloid beta-Peptides, Cell Survival, Organic Chemistry, Clinical Biochemistry, Pharmaceutical Science, Biochemistry, Rats, Enzyme Activation, Pyridazines, Inhibitory Concentration 50, Structure-Activity Relationship, Drug Discovery, Molecular Medicine, Animals, Humans, Amyloid Precursor Protein Secretases, Molecular Biology, Cells, Cultured
Abstract

SAR of a novel series of pyridazine-derived γ-secretase modulators is described. Compound 25 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aβ42 and Aβ40, and maintain the levels of total Aβ. Furthermore, 25 demonstrated excellent pharmacokinetic parameters as well as good CNS penetration in the rat.

Published
2011

Catalog

Books, media, physical & digital resources
See catalog results