Sotrastaurin

Base Information

• Chemical Name: Sotrastaurin
• CAS No.: 425637-18-9
• Molecular Formula: C25H22N6O2
• Molecular Weight: 438.48118
• UNII: 7I279E1NZ8
• DSSTox Substance ID: DTXSID70915192
• Nikkaji Number: J2.876.843E
• Wikidata: Q26331952
• NCI Thesaurus Code: C80630
• Pharos Ligand ID: QGASR1C53UZ5
• Metabolomics Workbench ID: 153367
• ChEMBL ID: CHEMBL565612
• Mol file: 425637-18-9.mol

Synonyms:AEB071;sotrastaurin

Chemical Property of Sotrastaurin

Chemical Property:

• PKA: 7.39±0.60(Predicted)
• PSA: 97.71000
• Density: 1.407 g/cm³
• LogP: 2.70890
• Solubility.: ≥21.9 mg/mL in DMSO; insoluble in H2O; ≥2.55 mg/mL in EtOH with ultrasonic
• XLogP3: 2.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 438.18042397
• Heavy Atom Count: 33
• Complexity: 822

Purity/Quality:

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

Sotrastaurin ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN1CCN(CC1)C2=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65
• Recent ClinicalTrials: Trial of AEB071 in Combination With BYL719 in Patients With Melanoma
• Recent EU Clinical Trials: An Open-Label, Single-arm, Phase Ib/II study of AEB071 (a Protein Kinase C Inhibitor) and Everolimus (mTOR inhibitor) in Patients with CD79-mutant or ABC subtype Diffuse Large B-Cell Lymphoma
• Description: Sotrastaurin (AEB071) is a potent and selective pan-PKC inhibitor, most potent against PKCθ with Ki of 0.22 nM in a cell-free assay; no activity against PKCζ.
• Uses: A potent selective pan-PKC inhibitor and highly inhibits PKCθ with a Ki of 0.22 nM. Sotrastaurin is an protein kinase C inhibitor that modulates migration and superoxide anion production by human neutrophils in vitro.

Technology Process of Sotrastaurin

There total 4 articles about Sotrastaurin 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: 47.0%

2-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-acetamide (425638-73-9) → sotrastaurin (425637-18-9)

Guidance literature:

With potassium tert-butylate; In tetrahydrofuran; at 0 - 20 ℃;

DOI:10.1021/jm901108b

Reference yield:

2-(2-chloroquinazolin-4-yl)acetamide (425638-74-0) → sotrastaurin (425637-18-9)

Guidance literature:

Multi-step reaction with 2 steps

1: 1-methyl-pyrrolidin-2-one / 0.75 h / 50 °C / Inert atmosphere

2: potassium tert-butylate / tetrahydrofuran / 0 - 20 °C / Inert atmosphere

With potassium tert-butylate; In tetrahydrofuran; 1-methyl-pyrrolidin-2-one;

DOI:10.1021/jm200469u

Reference yield:

2,4-dichloroquinazoline (607-68-1) → sotrastaurin (425637-18-9)

Guidance literature:

Multi-step reaction with 3 steps

1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 °C / Inert atmosphere

1.2: 0.5 h / 110 °C / Inert atmosphere

2.1: 1-methyl-pyrrolidin-2-one / 0.75 h / 50 °C / Inert atmosphere

3.1: potassium tert-butylate / tetrahydrofuran / 0 - 20 °C / Inert atmosphere

With potassium tert-butylate; sodium hydride; In tetrahydrofuran; 1-methyl-pyrrolidin-2-one; mineral oil;

DOI:10.1021/jm200469u

upstream raw materials:

2-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-acetamide

2-(2-chloroquinazolin-4-yl)acetamide

2,4-dichloroquinazoline

1,2,3,4-tetrahydro-quinazoline-2,4-dione

Downstream raw materials:

3-(1H-indol-3-yl)-4-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-1H-pyrrole-2,5-dione acetate

Refernces

• 1、 Wagner, Jürgen,Von Matt, Peter,Sedrani, Richard,Albert, Rainer,Cooke, Nigel,Ehrhardt, Claus,Geiser, Martin,Rummel, Gabriele,Stark, Wilhelm,Strauss, Andre,Cowan-Jacob, Sandra W.,Beerli, Christian,Weckbecker, Gisbert,Evenou, Jean-Pierre,Zenke, Gerhard,Cottens, Sylvain. "Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4- yl]-pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes". supporting information; experimental part. p. 6193 - 6196. Retrieved 2010/04/02.