Birabresib

Base Information

• Chemical Name: Birabresib
• CAS No.: 202590-98-5
• Molecular Formula: C25H22ClN5O2S
• Molecular Weight: 491.99248
• UNII: X40LKS49S3
• DSSTox Substance ID: DTXSID701103937
• Nikkaji Number: J3.437.919J
• Wikipedia: Birabresib
• Wikidata: Q27075296
• NCI Thesaurus Code: C103298
• Pharos Ligand ID: FWRXXS6LMF7G
• Metabolomics Workbench ID: 155328
• ChEMBL ID: CHEMBL3581647
• Mol file: 202590-98-5.mol

Synonyms:OTX015

Chemical Property of Birabresib

Chemical Property:

• Melting Point: 220 °C
• PKA: 10.05±0.26(Predicted)
• PSA: 120.64000
• Density: 1.45±0.1 g/cm3(Predicted)
• LogP: 5.04250
• Storage Temp.: 2-8°C
• Solubility.: ≥24.6 mg/mL in DMSO; insoluble in H2O; ≥106 mg/mL in EtOH with gentle warming
• XLogP3: 4.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 4
• Exact Mass: 491.1182738
• Heavy Atom Count: 34
• Complexity: 770

Purity/Quality:

99% ^*data from raw suppliers

(S)-2-(4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)O)C5=CC=C(C=C5)Cl)C
• Isomeric SMILES: CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)O)C5=CC=C(C=C5)Cl)C
• Recent ClinicalTrials: A Dose Exploration Study With Birabresib (MK-8628) in Participants With Selected Hematologic Malignancies (MK-8628-005)
• Recent EU Clinical Trials: A Phase IB Dose Exploration Trial with MK-8628, a Small Molecule Inhibitor of the Bromodomain and Extra-Terminal (BET) Proteins, in Subjects with Selected Advanced Solid Tumors
• Description: OTX015 is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Phase 1. The bromodomain and extra terminal domain (BET) family of proteins, including BRD2, BRD3, and BRD4, play a key role in many cellular processes, including inflammatory gene expression, mitosis, and viral/host interaction by controlling the assembly of histone acetylation-dependent chromatin complexes. OTX015 is an orally bioavailable, small molecule inhibitor of BRD2, BRD3, and BRD4 (EC50s = 10-19 nM). It displays antiproliferative effects at a sub-micromolar range in vitro in a wide range of solid tumor types and leukemias, downregulating c-Myc expression and inducing cell cycle arrest and apoptosis. At 100 mg/kg, OTX015 has been shown to inhibit the growth of Ty82 BRD-NUT midline carcinoma tumors in nude mice by 79%.
• Uses: (S)-2-(4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide is an orally bioavailable, inhibitor of BRD2, BRD3, and BRD4 to AcH4 and shows anti-tumor activity in vitro and in vivo tumor models.

Technology Process of Birabresib

There total 7 articles about Birabresib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 45.53%

(R)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid (202592-24-3,202592-23-2) + 4-amino-phenol (123-30-8) → (R)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide (202590-98-5)

Guidance literature:

With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20 ℃; for 17h;

Reference yield:

(S)-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetic acid (202592-23-2) + pivaloyl chloride (3282-30-2) + 4-amino-phenol (123-30-8) → (S)-2-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(4-hydroxyphenyl)acetamide (202590-98-5)

Guidance literature:

With triethylamine; In tetrahydrofuran; N-methyl-acetamide;

Reference yield:

methyl (3R)-3-[[3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl]carbamoyl]-3-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propanoate → (R)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-hydroxyphenyl)acetamide (202590-98-5)

Guidance literature:

Multi-step reaction with 5 steps

1.1: triethylamine / dichloromethane / 17 h / 40 °C

1.2: 2 h / 60 °C

2.1: tetraphosphorus decasulfide; sodium carbonate / toluene / 17 h / 110 °C

3.1: hydrazine hydrate / tetrahydrofuran / 1 h / 0 °C

3.2: 0.5 h / 0 °C

3.3: 4 h / 40 °C

4.1: lithium hydroxide; water; methanol / 2 h / 40 °C

5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 17 h / 20 °C

With methanol; tetraphosphorus decasulfide; water; sodium carbonate; benzotriazol-1-ol; hydrazine hydrate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; N-ethyl-N,N-diisopropylamine; lithium hydroxide; In tetrahydrofuran; dichloromethane; N,N-dimethyl-formamide; toluene;

upstream raw materials:

(S)-[4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetic acid

pivaloyl chloride

4-amino-phenol

(R)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid

Refernces

• 1、 -. "THIENOTRIAZOLODIAZEPINE COMPOUNDS AND MEDICINAL USES THEREOF". . . Retrieved 2008/06/13.