| abstract |
The present disclosure describes tert-butyl (S) -2- (4- (phenyl) -6H-thieno [3,2-f] [1,2,4] as a bromodomain BRD4 inhibitor for the treatment of cancer. ] Triazolo [4,3-a] [1,4] diazepine-6-yl) acetate derivatives and related compounds. Exemplified compounds are, for example, tert-butyl (S) -2- (4- (4- (3-aminoprop-1-in-1-yl) phenyl) -2,3,9-trimethyl-6H-thieno [3, 2-f] [1,2,4] triazolo [4,3-a] [1,4] diazepine-6-yl) acetate (Example 1, compound 1a), tert-butyl (S, E) -2 -(4- (4- (3-Aminopropa-1-en-1-yl) phenyl) -2,3,9-trimethyl-6H-thieno [3,2-f] [1,2,4] triazolo [ 4,3-a] [1,4] diazepine-6-yl) acetate (Example 6, compound 6a) or tert-butyl (S) -2- (4- (4- (3- (hydroxyamino)) ) Propa-1-in-1-yl) Phenyl) -2,3,9-trimethyl-6H-thieno [3,2-f] [1,2,4] Triazolo [4,3-a] [1, 4] Diazepine-6-yl) acetate (Example 8, compound 8a). The results of biological assays such as BRD4 BD1 and BD2 binding (Table 2), cell proliferation assay (Table 6), and inhibition of MYC expression in MV-4-11 cells (Table 7) are disclosed. [Selection diagram] None |