I-BET151 (GSK1210151A)

Base Information

• Chemical Name: I-BET151 (GSK1210151A)
• CAS No.: 1300031-49-5
• Molecular Formula: C23H21N5O3
• Molecular Weight: 415.44454
• Hs Code.: 2934999090
• Mol file: 1300031-49-5.mol

Synonyms:7-(3,5-Dimethyl-4-isoxazolyl)-1,3-dihydro-8-methoxy-1-[(1R)-1-(2-pyridinyl)ethyl]-2H-imidazo[4,5-c]quinolin-2-one;GSK 1210151A;I-BET 151;I-BET 151/GSK 1210151A;GSK1210151A (I-BET151);7-(3,5-diMethylisoxazol-4-yl)-8-Methoxy-1-((R)-1-(pyridin-2-yl)ethyl)-1H-iMidazo[4,5-c]quinolin-2(3H)-one;7-(3,5-Dimethylisoxazol-4-yl)-8-methoxy-1-((R)-1-(pyridin-2-yl)ethyl)-1H-imidazo[4,5-c]quinolin-2

Chemical Property of I-BET151 (GSK1210151A)

Chemical Property:

• PKA: 11.14±0.20(Predicted)
• PSA: 98.83000
• Density: 1.314
• LogP: 4.16250
• Storage Temp.: 2-8°C
• Solubility.: DMSO: soluble20mg/mL, clear

Purity/Quality:

98%,99%, ^*data from raw suppliers

I-BET151 ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 25
• Safety Statements: 45

MSDS Files:

SDS file from LookChem

Useful:

• Description: 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. I-BET151 is an isoxazole class pan-BET family inhibitor, blocking BRD2, BRD3, and BRD4 with IC50 values of 0.5, 0.25, and 0.79 μM, respectively. Through this action, it blocks the growth of leukemic cell lines driven by mixed lineage leukemia (MLL) fusions at nanomolar concentrations, whereas tyrosine kinase activated cells were much less sensitive. Specifically, I-BET151 induces apoptosis via reduced expression of BCL2 or triggers G0/G1 cell cycle arrest in MLL-fusion cell lines. I-BET151 is effective in vivo, suppressing MLL leukemia progression in two different mouse models.
• Uses: I-BET 151 is part of a novel series of quinoline isoxazole BET family bromodomain inhibitors, a family of four proteins that selectively bind to aceylated lysine residues in histone. I-BET 151 play ke y roles in many cellular processes, including anti-inflammatory gene expression, mitosis, and viral/host interaction by controlling the conformation of histone acetylation -dependent chromatin complex es. Studies have shown that I-BET 151 increased ApoA1 expression within the nanomolar range in human hepatic cell line HepG2. The upregulation by I-BET 151 suggested potential anti-inflammatory activi ties upon administration. GSK1210151A or I-BET151 has been used to study its inhibitory effect on BET (bromodomain and extra terminal) recruitment to chromatin in treating MLL (mixed-lineage leukemia)-fusion leukemia.

Technology Process of I-BET151 (GSK1210151A)

There total 17 articles about I-BET151 (GSK1210151A) 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: 95.46%

7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[(1R)-1-(2-pyridinyl)ethyl]amino}-3-quinolinecarboxamide (1300737-69-2) → I-BET151 (1300031-49-5)

Guidance literature:

With [bis(acetoxy)iodo]benzene; potassium hydroxide; In methanol; at 0 ℃; for 1h;

Reference yield: 33.0%

→ I-BET151 (1300031-49-5)

Guidance literature:

Reference yield:

3,5-dimethylisoxazole-4-boronic acid (16114-47-9) → I-BET151 (1300031-49-5)

Guidance literature:

Multi-step reaction with 9 steps

1: caesium carbonate / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere

2: palladium on activated charcoal; hydrogen; sodium sulfite / ethanol; ethyl acetate / 24 h

3: 1 h / 130 °C

4: diphenylether / 0.75 h / 255 °C

5: sodium hydroxide / ethanol / Reflux

6: trichlorophosphate / 4 h / Heating

7: ammonium hydroxide / tetrahydrofuran / 0.5 h / Cooling with ice

8: N-ethyl-N,N-diisopropylamine / 1-methyl-pyrrolidin-2-one / 120 °C

9: [bis(acetoxy)iodo]benzene; potassium hydroxide / methanol / 1.33 h / Cooling with ice

With ammonium hydroxide; diphenylether; [bis(acetoxy)iodo]benzene; palladium on activated charcoal; hydrogen; caesium carbonate; N-ethyl-N,N-diisopropylamine; potassium hydroxide; sodium hydroxide; sodium sulfite; trichlorophosphate; In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; methanol; 1,2-dimethoxyethane; ethanol; water; ethyl acetate; 1: Suzuki coupling / 9: Hofmann rearrangement;

DOI:10.1016/j.bmcl.2012.01.125

upstream raw materials:

3,5-dimethylisoxazole-4-boronic acid

2-iodo-1-methoxy-4-nitrobenzene

3,5-dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazole

[3-(3,5-dimethyl-4-isoxazolyl)-4-(methyloxy)phenyl]amine

Refernces

• 1、 Mirguet, Olivier,Lamotte, Yann,Donche, Frédéric,Toum, Jér?me,Gellibert, Franoise,Bouillot, Anne,Gosmini, Romain,Nguyen, Van-Loc,Delannée, Delphine,Seal, Jonathan,Blandel, Florence,Boullay, Anne-Bénédicte,Boursier, Eric,Martin, Sandrine,Brusq, Jean-Marie,Krysa, Gael,Riou, Alizon,Tellier, Rémi,Costaz, Agns,Huet, Pascal,Dudit, Yann,Trottet, Lionel,Kirilovsky, Jorge,Nicodeme, Edwige. "From ApoA1 upregulation to BET family bromodomain inhibition: Discovery of I-BET151". . p. 2963 - 2967. Retrieved 2012/06/04.
• 2、 -. "Bromodomain Inhibitors For Treating Autoimmune And Inflammatory Diseases". . . Retrieved 2012/08/28.