Kenpaullone

Base Information

• Chemical Name: Kenpaullone
• CAS No.: 142273-20-9
• Molecular Formula: C₁₆H₁₁BrN₂O
• Molecular Weight: 327.18
• European Community (EC) Number: 634-310-8
• NSC Number: 664704
• UNII: T72H2BL53P
• DSSTox Substance ID: DTXSID10161994
• Nikkaji Number: J485.726G
• Wikidata: Q72486910
• Pharos Ligand ID: QVTR7Q4R8PLQ
• Metabolomics Workbench ID: 144637
• ChEMBL ID: CHEMBL296586
• Mol file: 142273-20-9.mol

Synonyms:1-azakenpaullone;9-bromo-7,12-dihydroindolo(3,2-d)(1)benzazepin-6(5H)-one;kenpaullone;NSC 664704;NSC-664704

Chemical Property of Kenpaullone

Chemical Property:

• Appearance/Colour: tan solid
• Vapor Pressure: 5.82E-15mmHg at 25°C
• Melting Point: >300°C (dec.)
• Refractive Index: 1.73
• Boiling Point: 612.954 °C at 760 mmHg
• Flash Point: 324.503 °C
• PSA: 44.89000
• Density: 1.596 g/cm³
• LogP: 4.23000
• Storage Temp.: 2-8°C
• Solubility.: DMSO: 18 mg/mL, clear, yellow
• XLogP3: 3.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 0
• Exact Mass: 326.00548
• Heavy Atom Count: 20
• Complexity: 402

Purity/Quality:

99% ^*data from raw suppliers

Kenpaullone ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: C1C2=C(C3=CC=CC=C3NC1=O)NC4=C2C=C(C=C4)Br
• Description: Kenpaullone (142273-20-9) inhibits GSK-3β (IC50=0.23 μM) as well as several cyclin-dependent kinases (CDKs), IC50=0.4, 0.68 and 0.85 μM for cdk1, cdk2 and cdk5 respectively.1-3 Induces pluripotent stem cells from somatic cells4 and increases direct neural conversion of human fibroblasts5 when used with other small molecules. Inhibits Kruppel-Like Factor 4 (KLF4) reducing autoimmune arthritis in the collagen-induced arthritis mouse model.6
• Uses: The paullones are a novel class of kinase inhibitors, initially identified as CDK inhibitors. Kenpaullone has been found to be a useful GSK-3? inhibitor (IC50=23nM). Kenpaullone has been used:as a glycogen synthase kinase 3 (GSK3)/ cyclin-dependent kinase (CDK) inhibitor to study its effects on human neural progenitor cell linesas an inhibitor of Krupple-like factor 4 (KLF4) in Gs-coupled designer GPCR (Gs DREADD= GsD) Agouti-related peptide (GsD-AgRP) miceas a GSK3/CDK inhibitor to study its effects on the sea urchin embryo development The paullones are a novel class of kinase inhibitors, initially identified as CDK inhibitors. Kenpaullone has been found to be a useful GSK-3?inhibitor (IC50=23nM).

Technology Process of Kenpaullone

There total 22 articles about Kenpaullone 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: 100.0%

methyl 2-[5-bromo-2-(2-nitrophenyl)-1H-indol-3-yl]acetate → kenpaullone (142273-20-9)

Guidance literature:

With acetic acid; zinc; In methanol; at 60 ℃; Inert atmosphere;

DOI:10.1055/s-0036-1588749

Reference yield: 89.0%

methyl 2-(5-bromo-2-iodoindol-3-yl)acetate (1361550-29-9) + 2-anilineboronic acid pinacol ester (191171-55-8) → kenpaullone (142273-20-9)

Guidance literature:

With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; caesium carbonate; copper(l) chloride; In N,N-dimethyl-formamide; at 80 ℃; for 2h; Inert atmosphere;

DOI:10.1039/c2ob06695e

Reference yield: 79.6%

1H-[1]benzazepin-2,5(3H,4H)-dione (16511-38-9) + 4-bromophenylhydrazine hydrochloride (622-88-8,41931-18-4) → kenpaullone (142273-20-9)

Guidance literature:

1H-[1]benzazepin-2,5(3H,4H)-dione; 4-bromophenylhydrazine hydrochloride; With sodium acetate; acetic acid; at 70 ℃; for 3h;

With sulfuric acid; at 70 ℃; for 3h;

With sodium acetate; In water;

upstream raw materials:

1H-[1]benzazepin-2,5(3H,4H)-dione

(4-bromophenyl)hydrazine

4-bromophenylhydrazine hydrochloride

2-oxoindole

Downstream raw materials:

9-bromo-7,12-dihydroindolo[3,2-d ][1]benzazepin-6(5H)-thione

9-bromo-5-(4-methoxybenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one

9-bromo-5-(4-methylbenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one

9-bromo-5-(3,4-dichlorobenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one

Refernces

Identification of 2-anilino-9-methoxy-5, 7-dihydro-6H-pyrimido[5, 4-d][l]benzazepin-6-ones as dual PLK1/VEGF-R2 kinase inhibitor chemotypes by structure-based lead generation

10.1021/jm901388c

The study presents the identification and development of dual PLK1/VEGF-R2 kinase inhibitors based on the 2-anilino-9-methoxy-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-ones chemotype. Researchers explored the potential of the d-annulated 1-benzazepin-2-one scaffold, found in the paullone family of kinase inhibitors, as a template for designing inhibitors that could target both PLK1 and VEGF-R2. They synthesized and tested various scaffolds, finding that those with a 9-methoxy group on the scaffold showed additional PLK1 inhibitory activity beyond their VEGFR2 inhibition. The study includes detailed synthetic methods, biological evaluations, and molecular docking studies to understand the binding modes of the compounds. The most promising compounds were found to inhibit VEGF-R2 autophosphorylation in human umbilical vein endothelial cells, sprouting of endothelial cell speroids, and proliferation of various cancer cell lines, offering a potential therapeutic approach for cancer treatment by targeting both cell division and tumor vascularization.