The design, synthesis and structure-activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKKepsilon pathway in inflammatory diseases.
Author(s):
McIver, E. G., Bryans, J., Birchall, K., Chugh, J., Drake, T., Lewis, S. J., Osborne, J., Smiljanic-Hurley, E., Tsang, W., Kamal, A., Levy, A., Newman, M., Taylor, D., Arthur, J. S., Clark, K., Cohen, P.
PubMed:
23099093
Citation:
McIver, E. G., Bryans, J., Birchall, K., Chugh, J., Drake, T., Lewis, S. J., Osborne, J., Smiljanic-Hurley, E., Tsang, W., Kamal, A., Levy, A., Newman, M., Taylor, D., Arthur, J. S., Clark, K., Cohen, P.
McIver, E. G., Bryans, J., Birchall, K., Chugh, J., Drake, T., Lewis, S. J., Osborne, J., Smiljanic-Hurley, E., Tsang, W., Kamal, A., Levy, A., Newman, M., Taylor, D., Arthur, J. S., Clark, K., Cohen, P.
Bioorg Med Chem Lett
2012
22
7169-7173
PMID: 23099093