142273-20-9

Hazards Identification

Pictogram(s):

Signal:

Warning

GHS Hazard Statements:

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]
H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes:

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

Hazard Classes and Categories:

Skin Irrit. 2 (100%)
Eye Irrit. 2 (100%)
STOT SE 3 (100%)

Usage

Uses

Used in Pharmaceutical Research:
KENPAULLONE is used as a GSK-3β/CDK inhibitor for studying its effects on human neural progenitor cell lines, the sea urchin embryo development, and as an inhibitor of KLF4 in Gs-coupled designer GPCR (Gs DREADD) Agouti-related peptide (GsD-AgRP) mice.
Used in the Biochemical Industry:
KENPAULLONE is used as a potent inhibitor of various kinases, including GSK-3β, Lck, and Cdks, for research purposes and the development of new therapeutic strategies.
Used in the Biotechnology Industry:
KENPAULLONE is used to induce pluripotent stem cells from somatic cells and increase direct neural conversion of human fibroblasts when used with other small molecules, contributing to advancements in regenerative medicine and cell therapy.
Used in the Chemical Industry:
KENPAULLONE, being a tan solid, is used in the synthesis and development of new compounds with potential applications in various fields, including pharmaceuticals and materials science.

Biological Activity

Potent inhibitor of CDK1/cyclin B and GSK-3 β (IC 50 values are 0.4 and 0.23 μ M respectively). Also inhibits CDK2/cyclin A, CDK2/cyclin E and CDK5/cyclin/p35 (IC 50 values are 0.68, 7.5 and 0.85 μ M respectively). Selective over c-src (IC 50 = 15 μ M), casein kinase 2 (IC 50 = 20 μ M), ERK1 (IC 50 = 20 μ M), ERK2 (IC 50 = 9 μ M) and a range of other protein kinases (IC 50 values > 35 μ M). Generates induced pluripotent stem cells (iPSCs) from somatic cells when used in combination with reprogramming factors; can replace Klf4.

Biochem/physiol Actions

Kenpaullone is also an inhibitor of glycogen synthase kinase 3β (GSK3β).?It also inhibits cyclin-dependent kinase 1 (CDK1/cyclin B), CDK2/cyclin A, CDK2/cyclin E, and CDK5/p25, majorly by competitive inhibition of adenosine triphosphate (ATP) binding.

References

Zaharevitz et al. (1999), Discovery and initial characterization of the paullones, a novel class of small-molecule inhibitors of cyclin-dependent kinases; Cancer Res. 59 2566 Schultz et al. (1999) Paullones, a series of cyclin-dependent kinase inhibitor: synthesis, evaluation of CDK1/cyclin B inhibition, and in vitro antitumor activity; J.Med.Chem. 42 2909 Bain et al. (2003), The specificities of protein kinase inhibitors: an update; J. 371(Pt. 1) 199 Lyssiotis et al. (2009) Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4; Natl. Acad. Sci. USA 106 8912 Pfisterer et al. (2016), Small molecules increase direct neural conversion of human fibroblasts; Rep. 6 38290 Choi et al. (2018), Kruppel-Like Factor 4 Positively Regulates Autoimmune Arthritis in Mouse Models and Rheumatoid Arthritis in Patients via Modulating Cell Survival and Inflammation Factors of Fibroblast-Like Synoviocyte; Immunol. 9 1339

InChI:InChI=1/C16H11BrN2O/c17-9-5-6-14-11(7-9)12-8-15(20)18-13-4-2-1-3-10(13)16(12)19-14/h1-7,19H,8H2,(H,18,20)

Upstream product

• 16511-38-9 1H-[1]benzazepin-2,5(3H,4H)-dione 
• 589-21-9 (4-bromophenyl)hydrazine 
• 622-88-8 4-bromophenylhydrazine hydrochloride 
• 59-48-3 2-oxoindole 
• 20870-78-4 5-bromo-2-indolin-2-one 
• 1374335-74-6 1,N-di(tert-butoxycarbonyl)-5-bromo-2-chloro-N-(4-methoxyphenyl)indol-3-acetamide 
• 1391039-32-9 C₁₆H₁₀BrClN₂O₂ 
• 1374335-88-2 C₁₆H₁₂BrClN₂O 
• 552-89-6 2-nitro-benzaldehyde 
• 71205-21-5 methyl (E)-3-(2-amino-5-bromophenyl)prop-2-enoate 
• 1361550-29-9 methyl 2-(5-bromo-2-iodoindol-3-yl)acetate 
• 191171-55-8 2-anilineboronic acid pinacol ester 
• 10075-50-0 5-bromo-1H-indole 
• 117235-22-0 methyl 2-(5-bromo-1H-indole-3-yl)acetate 

Downstream Products

• 237430-35-2 9-bromo-7,12-dihydroindolo[3,2-d ][1]benzazepin-6(5H)-thione 
• 1213611-52-9 9-bromo-5-(3,4-dichlorobenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 
• 1213611-48-3 9-bromo-5-(4-methylbenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 
• 1213611-49-4 9-bromo-5-(4-methoxybenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 

Relevant academic research and scientific papers

Concise Total Syntheses of Paullone and Kenpaullone via Cyanide-Catalyzed Intramolecular Imino-Stetter Reaction

Highly concise total syntheses of paullone and kenpaullone were developed. Cyanide-catalyzed intramolecular imino-Stetter reaction of aldimines derived from methyl 2-aminocinnamate derivatives and 2-nitrobenzaldehyde provided 2-(2′-nitrophenyl)indole-3-acetic acid derivatives. Subsequent reduction of the nitro group with zinc under acidic conditions to an amino group followed by spontaneous lactam formation allowed for the total syntheses of paullone and kenpaullone to be completed in two steps starting from commercially available materials. The direct use of a nitro group as the precursor of an amino group present in the phenyl ring at the 2-position in the indole ring significantly streamlined the total syntheses of these target molecules..

New synthetic approach to paullones and characterization of their SIRT1 inhibitory activity

A series of 7,12-dihydroindolo[3,2-d][1]benzazepine-6(5H)-ones (paullones) substituted at C9/C10 (Br) and C2 (Me, CF3, CO2Me) have been synthesized by a one-pot Suzuki-Miyaura cross-coupling of an o-aminoarylboronic acid and methyl 2-iodoindoleacetate followed by intramolecular amide formation. Other approaches to the paullone scaffold based on Pd-catalyzed C-H activation were unsuccessful. In vitro enzymatic assay with recombinant human SIRT-1 indicated a strong inhibitory profile for the series, in particular the analogue with a methoxycarbonyl group at C2 and a bromine at C9. These compounds are, in general, inducers of granulocyte differentiation of the U937 acute leukemia cell line and cause a marked increase in pre-G1 of the cell cycle.

Synthesis of paullone and kenpaullone derivatives by photocyclization of 2-(2-chloro-1H-indol-3-yl)-N-arylacetamides

An efficient synthesis of paullone and kenpaullone derivatives in moderate to high yields has been achieved through photocyclizations of (2-chloro-1H-indole-3-yl)-N-arylacetamides in acetone at room temperature. Paullone and kenpaullone have been obtained

Development of 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters as selective inhibitors of mitochondrial malate dehydrogenase (mMDH)

A collection of paullones was tested for inhibitory activity against mitochondrial malate dehydrogenase (mMDH) as a biological target for antiproliferative activity. Based on the results of this screening, 5-benzylpaullones and paullone-9-carboxylic acid alkyl esters were developed as selective mMDH inhibitors. The new derivatives did not show noteworthy antiproliferative activity when tested on a panel of cancer cell lines, suggesting that mMDH inhibition is of minor relevance for the growth inhibition caused by paullones.

Tumor-inhibiting anellated azepinone derivatives

This invention relates to anellated azepinone derivatives, a method of their production, metal complexes of the anellated azepinone derivatives as well as their use in the treatment of tumor diseases.

PLANT GROWTH REGULATION

The present invention relates to a new class of plant growth regulators. In particular, the invention relates to fused azepinone derivative of general formula (I) or an agriculturally acceptable salt thereof wherein X is CO2R2 or H;

TUMOUR-INHIBITING ANNELLATED AZEPINONE DERIVATIVES

The invention relates to annellated azepinone derivatives, to a method for the production thereof, to metal complexes of the annellated azepinone derivatives, and to the use of the same for treating tumour diseases.

Synthesis of 7,12-Dihydro-indolo[3,2-d][1]benzazepin-6-(5H)-ones and 6,11-Dihydro-thieno-[3',2':2,3]azepino[4,5-b]indol-5(4H)-one

The title compounds 4 and 6 were prepared by Fischer indole synthesis. 4a is substituted in 10-position by reaction with bromine in glacial acetic acid. A fast ring inversion is observed for the azepine ring in 4 and 6.