(4S)-6-(4-Chlorophenyl)-N-ethyl-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-4-acetamide

GSK 525762A is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.

2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide is a benzodiazepine.|Molibresib is under investigation in clinical trial NCT01943851 (A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD) and Clinical Activity of GSK525762 in Subjects With Relapsed, Refractory Hematologic Malignancies).|Molibresib is a small molecule inhibitor of the BET (Bromodomain and Extra-Terminal) family of bromodomain-containing proteins with potential antineoplastic activity. Upon administration, molibresib binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histone peptides. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth. Characterized by a tandem repeat of bromodomain at the N-terminus, BET proteins, comprising of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.

2-[(4S)-6-(4-Chlorophenyl)-1 -methyl-8-(methyloxy)-4H-[1 , 2, 4]triazolo[4, 3- To a solution of [(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1 : 2-r(4S)-6-(4-Chlorophenyl)-1 -methyl-8-(methyloxy)-4H-ri , 2, 41triazolor4, 3- alH , 41benzodiazepin-4-yll-/V-ethylacetamide To a solution of Intermediate 2 (16.0 g, 40 mmol) in THF at RT was added DIEA (14 mL, 80 mmol) followed by HATU (30.4 g, 80 mmol). The reaction mixture was stirred for 3h at this temperature and ethylamine (40 mL, 2M in THF, 80 mmol) was added. The mixture was stirred for 48h before being concentrated under reduced pressure. The crude material was suspended in water and extracted with DCM. The organic layer was dried over Na2-[(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1, 2, 4]triazolo[4, 3-a][1, 4]benzodiazepin-4-yl]-N-ethylacetamide To a solution of [(4S)-6-(4-Chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1, 2, 4]triazolo[4, 3-a][1, 4]benzodiazepin-4-yl]acetic acid (for a preparation see Intermediate 1) (16.0 g, 40 mmol) in THF at RT was added DIEA (14 mL, 80 mmol) followed by HATU (30.4 g, 80 mmol). The reaction mixture was stirred for 3 h at this temperature and ethylamine (40 mL, 2M in THF, 80 mmol) was added. The mixture was stirred for 48 h before being concentrated under reduced pressure. The crude material was suspended in water and extracted with DCM. The organic layer was dried over NaExample 2

Molecular Weight:423.9
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:5
Exact Mass:423.1462027
Monoisotopic Mass:423.1462027
Topological Polar Surface Area:81.4
Heavy Atom Count:30
Complexity:639
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes