European Journal of Medicinal Chemistry (2020)
Update date:2022-08-17
Topics:
Hilton-Proctor, J. P.
Ilyichova, O.
Jennings, I. G.
Johnstone, R. W.
Mountford, S. J.
Scanlon, M. J.
Shortt, J.
Thompson, P. E.
Zheng, Z.
N-Methylpyrrolidone is one of several chemotypes that have been described as a mimetic of acetyl-lysine in the development of bromodomain inhibitors. In this paper, we describe the synthesis of a 4-phenyl substituted analogue – 1-methyl-4-phenylpyrrolidin-2-one – and the use of aryl substitution reactions as a divergent route for derivatives. Ultimately, this has led to structurally complex, chiral compounds with progressively improved affinity as inhibitors of bromodomain-containing protein 4.
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