Search Results - "Kemmitt, Paul"

A directed enolization strategy enables by-product-free construction of contiguous stereocentres en route to complex amino acids by Hong, Fenglin, Aldhous, Timothy P., Kemmitt, Paul D., Bower, John F.

“…Homochiral α-amino acids are widely used in pharmaceutical design as key subunits in chiral catalyst synthesis or as building blocks in synthetic biology. Many…”
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4‑π-Photocyclization of 1,2-Dihydropyridazines: An Approach to Bicyclic 1,2-Diazetidines with Rich Synthetic Potential by Britten, Thomas K, Kemmitt, Paul D, Halcovitch, Nathan R, Coote, Susannah C

“…The 4-π-photocyclization of a range of 1,2-dihydropyridazines is described, generating bicyclic 1,2-diazetidines in high yields on multigram scale. The key…”
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Development of a Novel B‑Cell Lymphoma 6 (BCL6) PROTAC To Provide Insight into Small Molecule Targeting of BCL6 by McCoull, William, Cheung, Tony, Anderson, Erica, Barton, Peter, Burgess, Jonathan, Byth, Kate, Cao, Qing, Castaldi, M. Paola, Chen, Huawei, Chiarparin, Elisabetta, Carbajo, Rodrigo J, Code, Erin, Cowan, Suzanna, Davey, Paul R, Ferguson, Andrew D, Fillery, Shaun, Fuller, Nathan O, Gao, Ning, Hargreaves, David, Howard, Martin R, Hu, Jun, Kawatkar, Aarti, Kemmitt, Paul D, Leo, Elisabetta, Molina, Daniel M, O’Connell, Nichole, Petteruti, Philip, Rasmusson, Timothy, Raubo, Piotr, Rawlins, Philip B, Ricchiuto, Piero, Robb, Graeme R, Schenone, Monica, Waring, Michael J, Zinda, Michael, Fawell, Stephen, Wilson, David M

“…B-cell lymphoma 6 (BCL6) inhibition is a promising mechanism for treating hematological cancers but high quality chemical probes are necessary to evaluate its…”
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Discovery of Pyrazolo[1,5‑a]pyrimidine B‑Cell Lymphoma 6 (BCL6) Binders and Optimization to High Affinity Macrocyclic Inhibitors by McCoull, William, Abrams, Roman D, Anderson, Erica, Blades, Kevin, Barton, Peter, Box, Matthew, Burgess, Jonathan, Byth, Kate, Cao, Qing, Chuaqui, Claudio, Carbajo, Rodrigo J, Cheung, Tony, Code, Erin, Ferguson, Andrew D, Fillery, Shaun, Fuller, Nathan O, Gangl, Eric, Gao, Ning, Grist, Matthew, Hargreaves, David, Howard, Martin R, Hu, Jun, Kemmitt, Paul D, Nelson, Jennifer E, O’Connell, Nichole, Prince, D. Bryan, Raubo, Piotr, Rawlins, Philip B, Robb, Graeme R, Shi, Junjie, Waring, Michael J, Whittaker, David, Wylot, Marta, Zhu, Xiahui

“…Inhibition of the protein–protein interaction between B-cell lymphoma 6 (BCL6) and corepressors has been implicated as a therapeutic target in diffuse large…”
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Tumour regression and improved gastrointestinal tolerability from controlled release of SN-38 from novel polyoxazoline-modified dendrimers by England, Richard M., Hare, Jennifer I., Barnes, Jennifer, Wilson, Joanne, Smith, Aaron, Strittmatter, Nicole, Kemmitt, Paul D., Waring, Michael J., Barry, Simon T., Alexander, Cameron, Ashford, Marianne B.

“…Irinotecan is used clinically for the treatment of colorectal cancer; however, its utility is limited by its narrow therapeutic index. We describe the use of a…”
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Discovery and In Vivo Efficacy of AZ-PRMT5i-1, a Novel PRMT5 Inhibitor with High MTA Cooperativity by Smith, James M., Barlaam, Bernard, Beattie, David, Bradshaw, Lauren, Chan, Ho Man, Chiarparin, Elisabetta, Collingwood, Olga, Cooke, Sophie L., Cronin, Anna, Cumming, Iain, Dean, Emma, Debreczeni, Judit É., del Barco Barrantes, Iván, Diene, Coura, Gianni, Davide, Guerot, Carine, Guo, Xiaoxiao, Guven, Sinem, Hayhow, Thomas G., Hong, Ted, Kemmitt, Paul D., Lamont, Gillian M., Lamont, Scott, Lynch, James T., McWilliams, Lisa, Moore, Shaun, Raubo, Piotr, Robb, Graeme R., Robinson, James, Scott, James S., Srinivasan, Bharath, Steward, Oliver, Stubbs, Christopher J., Syson, Karl, Tan, Lixiang, Turner, Oliver, Underwood, Elizabeth, Urosevic, Jelena, Vazquez-Chantada, Mercedes, Whittaker, Amy L., Wilson, David M., Winter-Holt, Jon J.

“…PRMT5, a type 2 arginine methyltransferase, has a critical role in regulating cell growth and survival in cancer. With the aim of developing MTA-cooperative…”
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Atom and step economical synthesis of acyclic quaternary centers via iridium-catalyzed hydroarylative cross-coupling of 1,1-disubstituted alkenes by Cooper, Phillippa, Dalling, Andrew G, Farrar, Elliot H E, Aldhous, Timothy P, Grélaud, Simon, Lester, Eleanor, Feron, Lyman J, Kemmitt, Paul D, Grayson, Matthew N, Bower, John F

“…Quaternary benzylic centers are accessed with high atom and step economy by Ir-catalyzed alkene hydroarylation. These studies provide unique examples of the…”
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Combining Sanford Arylations on Benzodiazepines with the Nuisance Effect by Khan, Raysa, Boonseng, Sarote, Kemmitt, Paul D., Felix, Robert, Coles, Simon J., Tizzard, Graham J., Williams, Gareth, Simmonds, Olivia, Harvey, Jessica‐Lily, Atack, John, Cox, Hazel, Spencer, John

“…5‐Phenyl‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐ones react under palladium‐ and visible light photoredox catalysis, in refluxing methanol, with aryldiazonium salts…”
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Design and optimisation of dendrimer-conjugated Bcl-2/xL inhibitor, AZD0466, with improved therapeutic index for cancer therapy by Patterson, Claire M., Balachander, Srividya B., Grant, Iain, Pop-Damkov, Petar, Kelly, Brian, McCoull, William, Parker, Jeremy, Giannis, Michael, Hill, Kathryn J., Gibbons, Francis D., Hennessy, Edward J., Kemmitt, Paul, Harmer, Alexander R., Gales, Sonya, Purbrick, Stuart, Redmond, Sean, Skinner, Matthew, Graham, Lorraine, Secrist, J. Paul, Schuller, Alwin G., Wen, Shenghua, Adam, Ammar, Reimer, Corinne, Cidado, Justin, Wild, Martin, Gangl, Eric, Fawell, Stephen E., Saeh, Jamal, Davies, Barry R., Owen, David J., Ashford, Marianne B.

“…Dual Bcl-2/Bcl-x L inhibitors are expected to deliver therapeutic benefit in many haematological and solid malignancies, however, their use is limited by…”
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Discovery of AZD4747, a Potent and Selective Inhibitor of Mutant GTPase KRASG12C with Demonstrable CNS Penetration by Kettle, Jason G., Bagal, Sharan K., Barratt, Derek, Bodnarchuk, Michael S., Boyd, Scott, Braybrooke, Erin, Breed, Jason, Cassar, Doyle J., Cosulich, Sabina, Davies, Michael, Davies, Nichola L., Deng, Chao, Eatherton, Andrew, Evans, Laura, Feron, Lyman J., Fillery, Shaun, Gleave, Emma S., Goldberg, Frederick W., Cortés González, Miguel A., Guerot, Carine, Haider, Afreen, Harlfinger, Stephanie, Howells, Rachel, Jackson, Anne, Johnström, Peter, Kemmitt, Paul D., Koers, Alex, Kondrashov, Mikhail, Lamont, Gillian M., Lamont, Scott, Lewis, Hilary J., Liu, Libin, Mylrea, Megan, Nash, Samuel, Niedbala, Michael J., Peter, Alison, Phillips, Christopher, Pike, Kurt, Raubo, Piotr, Robb, Graeme R., Ross, Sarah, Sanders, Matthew G., Schou, Magnus, Simpson, Iain, Steward, Oliver

“…The glycine to cysteine mutation at codon 12 of Kirsten rat sarcoma (KRAS) represents an Achilles heel that has now rendered this important GTPase druggable…”
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Discovery of AZD4747, a Potent and Selective Inhibitor of Mutant GTPase KRAS G12C with Demonstrable CNS Penetration by Kettle, Jason G, Bagal, Sharan K, Barratt, Derek, Bodnarchuk, Michael S, Boyd, Scott, Braybrooke, Erin, Breed, Jason, Cassar, Doyle J, Cosulich, Sabina, Davies, Michael, Davies, Nichola L, Deng, Chao, Eatherton, Andrew, Evans, Laura, Feron, Lyman J, Fillery, Shaun, Gleave, Emma S, Goldberg, Frederick W, Cortés González, Miguel A, Guerot, Carine, Haider, Afreen, Harlfinger, Stephanie, Howells, Rachel, Jackson, Anne, Johnström, Peter, Kemmitt, Paul D, Koers, Alex, Kondrashov, Mikhail, Lamont, Gillian M, Lamont, Scott, Lewis, Hilary J, Liu, Libin, Mylrea, Megan, Nash, Samuel, Niedbala, Michael J, Peter, Alison, Phillips, Christopher, Pike, Kurt, Raubo, Piotr, Robb, Graeme R, Ross, Sarah, Sanders, Matthew G, Schou, Magnus, Simpson, Iain, Steward, Oliver

“…The glycine to cysteine mutation at codon 12 of Kirsten rat sarcoma (KRAS) represents an Achilles heel that has now rendered this important GTPase druggable…”
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Late Stage CH Activation of a Privileged Scaffold; Synthesis of a Library of Benzodiazepines by Khan, Raysa, Felix, Robert, Kemmitt, Paul D., Coles, Simon J., Day, Iain J., Tizzard, Graham J., Spencer, John

“…A library of over twenty 5‐(2‐arylphenyl)‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐ones has been formed by a microwave‐mediated late‐stage palladium‐catalysed…”
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Deliberately Losing Control of C−H Activation Processes in the Design of Small‐Molecule‐Fragment Arrays Targeting Peroxisomal Metabolism by Khan Tareque, Raysa, Hassell‐Hart, Storm, Krojer, Tobias, Bradley, Anthony, Velupillai, Srikannathasan, Talon, Romain, Fairhead, Michael, Day, Iain J., Bala, Kamlesh, Felix, Robert, Kemmitt, Paul D., Brennan, Paul, Delft, Frank, Díaz Sáez, Laura, Huber, Kilian, Spencer, John

“…Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in…”
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Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRASG12C by Kettle, Jason G, Bagal, Sharan K, Bickerton, Sue, Bodnarchuk, Michael S, Breed, Jason, Carbajo, Rodrigo J, Cassar, Doyle J, Chakraborty, Atanu, Cosulich, Sabina, Cumming, Iain, Davies, Michael, Eatherton, Andrew, Evans, Laura, Feron, Lyman, Fillery, Shaun, Gleave, Emma S, Goldberg, Frederick W, Harlfinger, Stephanie, Hanson, Lyndsey, Howard, Martin, Howells, Rachel, Jackson, Anne, Kemmitt, Paul, Kingston, Jennifer K, Lamont, Scott, Lewis, Hilary J, Li, Songlei, Liu, Libin, Ogg, Derek, Phillips, Christopher, Polanski, Radek, Robb, Graeme, Robinson, David, Ross, Sarah, Smith, James M, Tonge, Michael, Whiteley, Rebecca, Yang, Junsheng, Zhang, Longfei, Zhao, Xiliang

“…Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRASG12C mutant…”
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Optimization of Brain Penetrant 11β-Hydroxysteroid Dehydrogenase Type I Inhibitors and in Vivo Testing in Diet-Induced Obese Mice by Goldberg, Frederick W, Dossetter, Alexander G, Scott, James S, Robb, Graeme R, Boyd, Scott, Groombridge, Sam D, Kemmitt, Paul D, Sjögren, Tove, Gutierrez, Pablo Morentin, deSchoolmeester, Joanne, Swales, John G, Turnbull, Andrew V, Wild, Martin J

“…11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II…”
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Discovery of a Potent, Selective, and Orally Efficacious Pyrimidinooxazinyl Bicyclooctaneacetic Acid Diacylglycerol Acyltransferase-1 Inhibitor by Birch, Alan M, Birtles, Susan, Buckett, Linda K, Kemmitt, Paul D, Smith, Graham J, Smith, Tim J. D, Turnbull, Andrew V, Wang, Steven J. Y

“…Inhibition of DGAT-1 is increasingly seen as an attractive mechanism with the potential for treatment of obesity and other elements of the metabolic syndrome…”
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Synthesis of 3‑(Hetero)aryl Tetrahydropyrazolo[3,4‑c]pyridines by Suzuki–Miyaura Cross-Coupling Methodology by Kemmitt, Paul D, Blades, Kevin, Box, Matthew R, Dickinson, Stephanie, Lamont, Gillian M, Madden, Katrina, McCoull, William, Williams, Jason

“…A new synthetic route to 3-(heteroaryl) tetrahydropyrazolo­[3,4-c]­pyridines has been developed that uses the Suzuki–Miyaura cross-coupling of a triflate 6…”
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Elaboration of tetra-orthogonally-substituted aromatic scaffolds towards novel EGFR-kinase inhibitors by Close, Adam J, Jones, Rhiannon N, Ocasio, Cory A, Kemmitt, Paul, Roe, S Mark, Spencer, John

“…Nitration of three regioisomers of bromo-fluorobenzaldehyde proceeds regioselectively, notably with H2SO4/HNO3 at 0 °C. The thereby synthesized…”
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Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687) by Barlind, Jonas G., Bauer, Udo A., Birch, Alan M., Birtles, Susan, Buckett, Linda K., Butlin, Roger J., Davies, Robert D. M., Eriksson, Jan W., Hammond, Clare D., Hovland, Ragnar, Johannesson, Petra, Johansson, Magnus J., Kemmitt, Paul D., Lindmark, Bo T., Morentin Gutierrez, Pablo, Noeske, Tobias A., Nordin, Andreas, O’Donnell, Charles J., Petersson, Annika U., Redzic, Alma, Turnbull, Andrew V., Vinblad, Johanna

“…A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and…”
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Optimized scale up of 3-pyrimidinylpyrazolo[1,5-a]pyridine via Suzuki coupling; a general method of accessing a range of 3-(hetero)arylpyrazolo[1,5-a]pyridines by Bethel, Paul A., Campbell, Andrew D., Goldberg, Frederick W., Kemmitt, Paul D., Lamont, Gillian M., Suleman, Abid

“…We have developed an improved synthesis of 3-(hetero)aryl pyrazolo[1,5-a]pyridines (such as 3-(2,5-dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine (8)) via an…”
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