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(1R,2R)-N-(1-cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole-2-carbonyl)cyclohexanecarboxamide (AZD4996): a potent and highly selective cathepsin K inhibitor for the treatment of osteoarthritis.
Dossetter AG, Beeley H, Bowyer J, Cook CR, Crawford JJ, Finlayson JE, Heron NM, Heyes C, Highton AJ, Hudson JA, Jestel A, Kenny PW, Krapp S, Martin S, MacFaul PA, McGuire TM, Gutierrez PM, Morley AD, Morris JJ, Page KM, Ribeiro LR, Sawney H, Steinbacher S, Smith C, Vickers M. Dossetter AG, et al. Among authors: highton aj. J Med Chem. 2012 Jul 26;55(14):6363-74. doi: 10.1021/jm3007257. Epub 2012 Jul 10. J Med Chem. 2012. PMID: 22742641
Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition.
Dossetter AG, Bowyer J, Cook CR, Crawford JJ, Finlayson JE, Heron NM, Heyes C, Highton AJ, Hudson JA, Jestel A, Krapp S, MacFaul PA, McGuire TM, Morley AD, Morris JJ, Page KM, Ribeiro LR, Sawney H, Steinbacher S, Smith C. Dossetter AG, et al. Among authors: highton aj. Bioorg Med Chem Lett. 2012 Sep 1;22(17):5563-8. doi: 10.1016/j.bmcl.2012.07.012. Epub 2012 Jul 15. Bioorg Med Chem Lett. 2012. PMID: 22858142
Pharmacokinetic benefits of 3,4-dimethoxy substitution of a phenyl ring and design of isosteres yielding orally available cathepsin K inhibitors.
Crawford JJ, Kenny PW, Bowyer J, Cook CR, Finlayson JE, Heyes C, Highton AJ, Hudson JA, Jestel A, Krapp S, Martin S, Macfaul PA, McDermott BP, McGuire TM, Morley AD, Morris JJ, Page KM, Ribeiro LR, Sawney H, Steinbacher S, Smith C, Dossetter AG. Crawford JJ, et al. Among authors: highton aj. J Med Chem. 2012 Oct 25;55(20):8827-37. doi: 10.1021/jm301119s. Epub 2012 Oct 11. J Med Chem. 2012. PMID: 22984809
Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle.
Mackman RL, Steadman VA, Dean DK, Jansa P, Poullennec KG, Appleby T, Austin C, Blakemore CA, Cai R, Cannizzaro C, Chin G, Chiva JC, Dunbar NA, Fliri H, Highton AJ, Hui H, Ji M, Jin H, Karki K, Keats AJ, Lazarides L, Lee YJ, Liclican A, Mish M, Murray B, Pettit SB, Pyun P, Sangi M, Santos R, Sanvoisin J, Schmitz U, Schrier A, Siegel D, Sperandio D, Stepan G, Tian Y, Watt GM, Yang H, Schultz BE. Mackman RL, et al. Among authors: highton aj. J Med Chem. 2018 Nov 8;61(21):9473-9499. doi: 10.1021/acs.jmedchem.8b00802. Epub 2018 Aug 22. J Med Chem. 2018. PMID: 30074795
Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice.
McNae IW, Kinkead J, Malik D, Yen LH, Walker MK, Swain C, Webster SP, Gray N, Fernandes PM, Myburgh E, Blackburn EA, Ritchie R, Austin C, Wear MA, Highton AJ, Keats AJ, Vong A, Dornan J, Mottram JC, Michels PAM, Pettit S, Walkinshaw MD. McNae IW, et al. Among authors: highton aj. Nat Commun. 2021 Feb 16;12(1):1052. doi: 10.1038/s41467-021-21273-6. Nat Commun. 2021. PMID: 33594070 Free PMC article.
Model studies for the synthesis of galbonolide B.
Eshelby J, Goessman M, Parsons PJ, Pennicott L, Highton A. Eshelby J, et al. Org Biomol Chem. 2005 Aug 21;3(16):2994-7. doi: 10.1039/b505378a. Epub 2005 Jul 4. Org Biomol Chem. 2005. PMID: 16186930
A total synthesis of galbonolide B.
Parsons PJ, Pennicott L, Eshelby J, Goessman M, Highton A, Hitchcock P. Parsons PJ, et al. J Org Chem. 2007 Nov 23;72(24):9387-90. doi: 10.1021/jo701509r. Epub 2007 Oct 24. J Org Chem. 2007. PMID: 17958371
26 results