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Discovery and optimization of C-2 methyl imidazopyrrolopyridines as potent and orally bioavailable JAK1 inhibitors with selectivity over JAK2.
Zak M, Mendonca R, Balazs M, Barrett K, Bergeron P, Blair WS, Chang C, Deshmukh G, Devoss J, Dragovich PS, Eigenbrot C, Ghilardi N, Gibbons P, Gradl S, Hamman C, Hanan EJ, Harstad E, Hewitt PR, Hurley CA, Jin T, Johnson A, Johnson T, Kenny JR, Koehler MF, Bir Kohli P, Kulagowski JJ, Labadie S, Liao J, Liimatta M, Lin Z, Lupardus PJ, Maxey RJ, Murray JM, Pulk R, Rodriguez M, Savage S, Shia S, Steffek M, Ubhayakar S, Ultsch M, van Abbema A, Ward SI, Xiao L, Xiao Y. Zak M, et al. Among authors: johnson t, johnson a. J Med Chem. 2012 Jul 12;55(13):6176-93. doi: 10.1021/jm300628c. Epub 2012 Jun 28. J Med Chem. 2012. PMID: 22698084
Identification of imidazo-pyrrolopyridines as novel and potent JAK1 inhibitors.
Kulagowski JJ, Blair W, Bull RJ, Chang C, Deshmukh G, Dyke HJ, Eigenbrot C, Ghilardi N, Gibbons P, Harrison TK, Hewitt PR, Liimatta M, Hurley CA, Johnson A, Johnson T, Kenny JR, Bir Kohli P, Maxey RJ, Mendonca R, Mortara K, Murray J, Narukulla R, Shia S, Steffek M, Ubhayakar S, Ultsch M, van Abbema A, Ward SI, Waszkowycz B, Zak M. Kulagowski JJ, et al. Among authors: johnson t, johnson a. J Med Chem. 2012 Jun 28;55(12):5901-21. doi: 10.1021/jm300438j. Epub 2012 Jun 11. J Med Chem. 2012. PMID: 22591402
Structure-based discovery of C-2 substituted imidazo-pyrrolopyridine JAK1 inhibitors with improved selectivity over JAK2.
Labadie S, Dragovich PS, Barrett K, Blair WS, Bergeron P, Chang C, Deshmukh G, Eigenbrot C, Ghilardi N, Gibbons P, Hurley CA, Johnson A, Kenny JR, Kohli PB, Kulagowski JJ, Liimatta M, Lupardus PJ, Mendonca R, Murray JM, Pulk R, Shia S, Steffek M, Ubhayakar S, Ultsch M, van Abbema A, Ward S, Zak M. Labadie S, et al. Among authors: johnson a. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7627-33. doi: 10.1016/j.bmcl.2012.10.008. Epub 2012 Oct 11. Bioorg Med Chem Lett. 2012. PMID: 23107482
Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1.
Hurley CA, Blair WS, Bull RJ, Chang C, Crackett PH, Deshmukh G, Dyke HJ, Fong R, Ghilardi N, Gibbons P, Hewitt PR, Johnson A, Johnson T, Kenny JR, Kohli PB, Kulagowski JJ, Liimatta M, Lupardus PJ, Maxey RJ, Mendonca R, Narukulla R, Pulk R, Ubhayakar S, van Abbema A, Ward SI, Waszkowycz B, Zak M. Hurley CA, et al. Among authors: johnson t, johnson a. Bioorg Med Chem Lett. 2013 Jun 15;23(12):3592-8. doi: 10.1016/j.bmcl.2013.04.018. Epub 2013 Apr 17. Bioorg Med Chem Lett. 2013. PMID: 23642482
Identification of C-2 hydroxyethyl imidazopyrrolopyridines as potent JAK1 inhibitors with favorable physicochemical properties and high selectivity over JAK2.
Zak M, Hurley CA, Ward SI, Bergeron P, Barrett K, Balazs M, Blair WS, Bull R, Chakravarty P, Chang C, Crackett P, Deshmukh G, DeVoss J, Dragovich PS, Eigenbrot C, Ellwood C, Gaines S, Ghilardi N, Gibbons P, Gradl S, Gribling P, Hamman C, Harstad E, Hewitt P, Johnson A, Johnson T, Kenny JR, Koehler MF, Bir Kohli P, Labadie S, Lee WP, Liao J, Liimatta M, Mendonca R, Narukulla R, Pulk R, Reeve A, Savage S, Shia S, Steffek M, Ubhayakar S, van Abbema A, Aliagas I, Avitabile-Woo B, Xiao Y, Yang J, Kulagowski JJ. Zak M, et al. Among authors: johnson t, johnson a. J Med Chem. 2013 Jun 13;56(11):4764-85. doi: 10.1021/jm4004895. Epub 2013 May 31. J Med Chem. 2013. PMID: 23659214
Lead optimization of a 4-aminopyridine benzamide scaffold to identify potent, selective, and orally bioavailable TYK2 inhibitors.
Liang J, van Abbema A, Balazs M, Barrett K, Berezhkovsky L, Blair W, Chang C, Delarosa D, DeVoss J, Driscoll J, Eigenbrot C, Ghilardi N, Gibbons P, Halladay J, Johnson A, Kohli PB, Lai Y, Liu Y, Lyssikatos J, Mantik P, Menghrajani K, Murray J, Peng I, Sambrone A, Shia S, Shin Y, Smith J, Sohn S, Tsui V, Ultsch M, Wu LC, Xiao Y, Yang W, Young J, Zhang B, Zhu BY, Magnuson S. Liang J, et al. Among authors: johnson a. J Med Chem. 2013 Jun 13;56(11):4521-36. doi: 10.1021/jm400266t. Epub 2013 May 29. J Med Chem. 2013. PMID: 23668484
Lead identification of novel and selective TYK2 inhibitors.
Liang J, Tsui V, Van Abbema A, Bao L, Barrett K, Beresini M, Berezhkovskiy L, Blair WS, Chang C, Driscoll J, Eigenbrot C, Ghilardi N, Gibbons P, Halladay J, Johnson A, Kohli PB, Lai Y, Liimatta M, Mantik P, Menghrajani K, Murray J, Sambrone A, Xiao Y, Shia S, Shin Y, Smith J, Sohn S, Stanley M, Ultsch M, Zhang B, Wu LC, Magnuson S. Liang J, et al. Among authors: johnson a. Eur J Med Chem. 2013 Sep;67:175-87. doi: 10.1016/j.ejmech.2013.03.070. Epub 2013 May 14. Eur J Med Chem. 2013. PMID: 23867602
A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors.
Sohn SJ, Barrett K, Van Abbema A, Chang C, Kohli PB, Kanda H, Smith J, Lai Y, Zhou A, Zhang B, Yang W, Williams K, Macleod C, Hurley CA, Kulagowski JJ, Lewin-Koh N, Dengler HS, Johnson AR, Ghilardi N, Zak M, Liang J, Blair WS, Magnuson S, Wu LC. Sohn SJ, et al. Among authors: johnson ar. J Immunol. 2013 Sep 1;191(5):2205-16. doi: 10.4049/jimmunol.1202859. Epub 2013 Jul 26. J Immunol. 2013. PMID: 23894201 Free PMC article.
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