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An integrated approach to fragment-based lead generation: philosophy, strategy and case studies from AstraZeneca's drug discovery programmes.
Albert JS, Blomberg N, Breeze AL, Brown AJ, Burrows JN, Edwards PD, Folmer RH, Geschwindner S, Griffen EJ, Kenny PW, Nowak T, Olsson LL, Sanganee H, Shapiro AB. Albert JS, et al. Among authors: olsson ll. Curr Top Med Chem. 2007;7(16):1600-29. doi: 10.2174/156802607782341091. Curr Top Med Chem. 2007. PMID: 17979771 Review.
Application of fragment-based lead generation to the discovery of novel, cyclic amidine beta-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency.
Edwards PD, Albert JS, Sylvester M, Aharony D, Andisik D, Callaghan O, Campbell JB, Carr RA, Chessari G, Congreve M, Frederickson M, Folmer RH, Geschwindner S, Koether G, Kolmodin K, Krumrine J, Mauger RC, Murray CW, Olsson LL, Patel S, Spear N, Tian G. Edwards PD, et al. Among authors: olsson ll. J Med Chem. 2007 Nov 29;50(24):5912-25. doi: 10.1021/jm070829p. Epub 2007 Nov 7. J Med Chem. 2007. PMID: 17985862
Synthesis and structure-activity relationship of 4-(1,3-benzothiazol-2-yl)-thiophene-2-sulfonamides as cyclin-dependent kinase 5 (cdk5)/p25 inhibitors.
Malmström J, Viklund J, Slivo C, Costa A, Maudet M, Sandelin C, Hiller G, Olsson LL, Aagaard A, Geschwindner S, Xue Y, Vasänge M. Malmström J, et al. Among authors: olsson ll. Bioorg Med Chem Lett. 2012 Sep 15;22(18):5919-23. doi: 10.1016/j.bmcl.2012.07.068. Epub 2012 Jul 25. Bioorg Med Chem Lett. 2012. PMID: 22889803
Design and synthesis of β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors with in vivo brain reduction of β-amyloid peptides.
Swahn BM, Kolmodin K, Karlström S, von Berg S, Söderman P, Holenz J, Berg S, Lindström J, Sundström M, Turek D, Kihlström J, Slivo C, Andersson L, Pyring D, Rotticci D, Ohberg L, Kers A, Bogar K, von Kieseritzky F, Bergh M, Olsson LL, Janson J, Eketjäll S, Georgievska B, Jeppsson F, Fälting J. Swahn BM, et al. Among authors: olsson ll. J Med Chem. 2012 Nov 8;55(21):9346-61. doi: 10.1021/jm3009025. Epub 2012 Sep 17. J Med Chem. 2012. PMID: 22924815
Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease.
Jeppsson F, Eketjäll S, Janson J, Karlström S, Gustavsson S, Olsson LL, Radesäter AC, Ploeger B, Cebers G, Kolmodin K, Swahn BM, von Berg S, Bueters T, Fälting J. Jeppsson F, et al. Among authors: olsson ll. J Biol Chem. 2012 Nov 30;287(49):41245-57. doi: 10.1074/jbc.M112.409110. Epub 2012 Oct 9. J Biol Chem. 2012. PMID: 23048024 Free PMC article.
New aminoimidazoles as β-secretase (BACE-1) inhibitors showing amyloid-β (Aβ) lowering in brain.
Gravenfors Y, Viklund J, Blid J, Ginman T, Karlström S, Kihlström J, Kolmodin K, Lindström J, von Berg S, von Kieseritzky F, Bogar K, Slivo C, Swahn BM, Olsson LL, Johansson P, Eketjäll S, Fälting J, Jeppsson F, Strömberg K, Janson J, Rahm F. Gravenfors Y, et al. Among authors: olsson ll. J Med Chem. 2012 Nov 8;55(21):9297-311. doi: 10.1021/jm300991n. Epub 2012 Oct 3. J Med Chem. 2012. PMID: 23017051
Aminoimidazoles as BACE-1 inhibitors: the challenge to achieve in vivo brain efficacy.
Swahn BM, Holenz J, Kihlström J, Kolmodin K, Lindström J, Plobeck N, Rotticci D, Sehgelmeble F, Sundström M, Berg Sv, Fälting J, Georgievska B, Gustavsson S, Neelissen J, Ek M, Olsson LL, Berg S. Swahn BM, et al. Among authors: olsson ll. Bioorg Med Chem Lett. 2012 Mar 1;22(5):1854-9. doi: 10.1016/j.bmcl.2012.01.079. Epub 2012 Jan 28. Bioorg Med Chem Lett. 2012. PMID: 22325942
18 results