R428

Base Information

• Chemical Name: R428
• CAS No.: 1037624-75-1
• Molecular Formula: C30H34N8
• Molecular Weight: 506.64456
• Mol file: 1037624-75-1.mol

Synonyms:R428;R428 (BGB324);1-(6,7-Dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazin-3-yl)-N3-[(7S)-6,7,8,9-tetrahydro-7-(1-pyrrolidinyl)-5H-benzocyclohepten-2-yl]-1H-1,2,4-triazole-3,5-diamine

Chemical Property of R428

Chemical Property:

• Boiling Point: 799.6±70.0 °C(Predicted)
• PKA: 10.34±0.20(Predicted)
• PSA: 98.51000
• Density: 1.41±0.1 g/cm3(Predicted)
• LogP: 4.82300
• Storage Temp.: -20°C
• Solubility.: Soluble in DMSO (up to at least 25 mg/ml)

Purity/Quality:

99% ^*data from raw suppliers

R428 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: R428 (bemcentinib, BGB324), a selective small-molecule inhibitor of AXL, is currently being evaluated in phase II trials for the treatment of non-small-cell lung cancer (NSCLC) and acute myelocytic leukemia (AML). It has been found to induce apoptosis in cancer cells and to block tumor spread in models of metastatic breast cancer. The therapeutic potential of R428 has also been demonstrated in highly invasive esophageal adenocarcinoma cells and in ESCC cells.R428 is a selective, small molecule inhibitor of Axl that blocks its catalytic and precancerous activities. R428 treatment reduced Axl-induced AKT phosphorylation, cancer cell invasion, angiogenesis, and the production of pro-inflammatory cytokines. It also reduced the expression of the cytokine granulocyte macrophage colony-stimulating factor and Snail in a dosage-dependent manner. Interestingly,using R428 to inhibit Axl-mediated cellular and molecular functions during cisplatin treatments achieved an enhanced suppression of liver metastases. Axl knockdowns in RAC cell lines reduced migration, invasion, and in vivo engraftment, accompanied by a downregulation in the activity of the Ral GTPase proteins (RalA and RalB). Similar effects were obtained using an A428 inhibitor. Blocking Axl functions also abrogated the phosphorylation of ERBB2 (Her-2/neu) at the Tyr877 residue, which reveals the cross-functional effects of R428 on different receptor signaling axes.Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)
• Uses: R 428 is an AXL tyrosine kinase inhibitor shown to be used as an anti-cancer agent.

Technology Process of R428

There total 13 articles about R428 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: 62.0%

1-(6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazine-3-yl)-N3-(7-(S)-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)-1H-1,2,4-triazole-3,5-diamine fumarate → R428 (1037624-75-1)

Guidance literature:

With sodium hydroxide; In ethanol; water; at 75 ℃; pH=9.1; Reagent/catalyst; Temperature; Cooling;

Reference yield:

α,α'-dibromo-o-xylene (91-13-4) → R428 (1037624-75-1)

Guidance literature:

Multi-step reaction with 7 steps

1.1: sodium methylate

2.1: potassium hydroxide / ethanol / 85 °C

3.1: nitric acid; sulfuric acid / nitromethane

4.1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane

5.1: hydrogen; palladium on activated charcoal / methanol

6.1: Resolution of racemate

6.2: Alkaline conditions

7.1: isopropyl alcohol

With sulfuric acid; palladium on activated charcoal; hydrogen; nitric acid; sodium methylate; sodium tris(acetoxy)borohydride; acetic acid; potassium hydroxide; In methanol; nitromethane; ethanol; 1,2-dichloro-ethane; isopropyl alcohol;

DOI:10.1358/dof.2018.043.09.2808543

Reference yield:

dimethyl 1,2,4,5-tetrahydro-3-oxobenzocycloheptene-2,4-dicarboxylate (24790-66-7) → R428 (1037624-75-1)

Guidance literature:

Multi-step reaction with 6 steps

1.1: potassium hydroxide / ethanol / 85 °C

2.1: nitric acid; sulfuric acid / nitromethane

3.1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane

4.1: hydrogen; palladium on activated charcoal / methanol

5.1: Resolution of racemate

5.2: Alkaline conditions

6.1: isopropyl alcohol

With sulfuric acid; palladium on activated charcoal; hydrogen; nitric acid; sodium tris(acetoxy)borohydride; acetic acid; potassium hydroxide; In methanol; nitromethane; ethanol; 1,2-dichloro-ethane; isopropyl alcohol;

DOI:10.1358/dof.2018.043.09.2808543

upstream raw materials:

phenyl (S)-N'-cyano-N-(7-(pyrrolidin-1-yl)-6,7,8,9-tetrahydro-5H-benzo[7]annulene-2-yl)carbamimidate

3-hydrazino-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazine

α,α'-dibromo-o-xylene

dimethyl 1,2,4,5-tetrahydro-3-oxobenzocycloheptene-2,4-dicarboxylate

Refernces

• 1、 -. "PROCESS FOR THE PURIFICATION OF THE AXL TYROSINE RECEPTOR KINASE INHIBITOR "R428"". . . Retrieved 2016/06/13.