| 摘要 |
A compound or a pharmaceutically acceptable salt or solvate thereof with a molecular weight in the range 100 to 750 which inhibits the binding of the first and/or second bromodomains of human BRD-2 to 4 to acetylated lysine residues of their physiological partner which is able to:
a) form a hydrogen bonding interaction in which the compound accepts a hydrogen bond from the sidechain NH2 group of the asparagine residue found at:
or
b) accept a water-mediated hydrogen bond in which the compound accepts a hydrogen bond from a water that is itself hydrogen-bonded to the sidechain hydroxyl of the tyrosine residue found at
and
c) which are also able to form a Van der Waals interaction with a lipophilic binding region of a binding pocket such that one or more heavy atoms of the said compounds lie within a 5A range of any of the heavy atoms of the following bromodomain residues which define the binding pocket:
for use in the treatment of chronic autoimmune and inflammatory conditions, acute inflammatory conditions or cancer. |
