6VUF

Crystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2-one (NMP) derivative 7h (4-(1-methyl-5-oxopyrrolidin-3-yl)-N-propylbenzenesulfonamide)

Summary for 6VUF

• Entry DOI: 10.2210/pdb6vuf/pdb
• Descriptor: Bromodomain-containing protein 4, 4-[(3R)-1-methyl-5-oxopyrrolidin-3-yl]-N-propylbenzene-1-sulfonamide (3 entities in total)
• Functional Keywords: brd4 bd1, bromodomain, nmp, protein binding
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 30529.13

Authors

Ilyichova, O.V.,Scanlon, M.J.,Thompson, P.E. (deposition date: 2020-02-15, release date: 2020-02-26, Last modification date: 2023-10-11)

Primary citation

Hilton-Proctor, J.P.,Ilyichova, O.,Zheng, Z.,Jennings, I.G.,Johnstone, R.W.,Shortt, J.,Mountford, S.J.,Scanlon, M.J.,Thompson, P.E.
Substituted 1-methyl-4-phenylpyrrolidin-2-ones - Fragment-based design of N-methylpyrrolidone-derived bromodomain inhibitors.
Eur.J.Med.Chem., 191:112120-112120, 2020

PubMed Abstract: 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.

PubMed: 32120339
DOI: 10.1016/j.ejmech.2020.112120

Experimental method

X-RAY DIFFRACTION (1.59 Å)