142273-18-5

Basic information

• Product Name: Paullone
• Synonyms: Paullone;7,12-Dihydroindolo[3,2-d][1]benzazepin-6(5H)-one
• CAS NO: 142273-18-5
• Molecular Formula: C₁₆H₁₂N₂O
• Molecular Weight: 247.27134
• Product Categories: Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 142273-18-5.mol

Chemical Properties

• Boiling Point: 571.2°C at 760 mmHg
• Flash Point: 299.2°C
• Appearance: /
• Density: 1.315g/cm³
• Vapor Pressure: 4.67E-13mmHg at 25°C
• Refractive Index: 1.714
• CAS DataBase Reference: Paullone(CAS DataBase Reference)
• NIST Chemistry Reference: Paullone(142273-18-5)
• EPA Substance Registry System: Paullone(142273-18-5)

Safety Data

• Hazardous Substances Data: 142273-18-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Applications:
Paullone is used as an inhibitor of CDKs for its ability to regulate the cell cycle. This application is particularly relevant in the development of treatments for cancer, as dysregulation of CDKs can lead to uncontrolled cell proliferation and tumor growth.
Used in Biotechnology Applications:
In the biotechnology industry, paullone is utilized as a research tool to study the role of CDKs in cellular processes. By inhibiting these kinases, researchers can gain insights into the mechanisms underlying cell cycle regulation and develop targeted therapies for various diseases.
Used in Drug Development:
Paullone's potent inhibition of CDKs makes it a valuable compound in the development of new drugs. It can be used as a starting point for the design of more selective and effective CDK inhibitors, which could have applications in cancer treatment and other conditions related to cell cycle dysregulation.
Used in Anticancer Applications:
Similar to gallotannin, paullone is employed as an anticancer agent due to its ability to modulate oncological signaling pathways. By targeting CDKs, paullone can inhibit tumor growth and progression, making it a potential therapeutic option for various types of cancer.
Used in Drug Delivery Systems:
To enhance the efficacy and bioavailability of paullone, drug delivery systems can be developed to improve its delivery to target cells. Organic and metallic nanoparticles can be used as carriers for paullone, aiming to increase its therapeutic outcomes and reduce potential side effects.

InChI:InChI=1/C16H12N2O/c19-15-9-12-10-5-1-3-7-13(10)18-16(12)11-6-2-4-8-14(11)17-15/h1-8,18H,9H2,(H,17,19)

Upstream product

• 10113-39-0 N-formyl-2-iodoaniline 
• 88939-75-7 methyl (2E)-3-(2-aminophenyl)propenoate 
• 6630-33-7 ortho-bromobenzaldehyde 
• 1912-35-2 methyl 2-(2-bromo-1H-indol-3-yl)acetate 
• 615-36-1 2-bromoaniline 
• 1160998-28-6 2-(2-bromo-benzylidene)-malonic acid dimethyl ester 
• 1620385-50-3 C₁₅H₁₅INO₂⁽¹⁺⁾*CF₃O₃S^(1-) 
• 275361-65-4 Methyl 2-(2-iodo-1H-indol-3-yl)acetate 
• 191171-55-8 2-anilineboronic acid pinacol ester 
• 1912-33-0 Indole-3-acetic acid methyl ester 
• 87-51-4 indole-3-acetic acid 
• 771-51-7 indole-3-acetonitrile 
• 1912-34-1 methyl 2-(2-chloro-1H-indol-3-yl)acetate 
• 1912-39-6 2-(2-bromoindol-3-yl)acetic acid 

Downstream Products

• 1213611-56-3 5-(3,4-dichlorobenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 
• 1213611-55-2 5-(4-methylbenzyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one 

Relevant articles and documents

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.

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..

A Synthesis of Multifunctionalized Indoles from [3 + 2] Annulation of 2-Bromocyclopropenes with Anilines

A new regioselective method for the synthesis of multifunctionalized indoles from [3 + 2] annulation of 2-bromocyclopropenes with anilines has been developed. By employing a nickel complex as a catalyst, 27 examples of indole products were obtained in goo

A Pd-catalyzed, boron ester-mediated, reductive cross-coupling of two aryl halides to synthesize tricyclic biaryls

Tricyclic biaryls are important scaffold structures in many natural products and lead compounds in drug discovery. The formation of a biaryl unit is often the key step for the synthesis of tricyclic biaryls. Despite significant progress toward the synthesis of biaryl compounds in recent years, the direct cross-coupling of two different aryl halides is still challenging and robust methods are lacking. Herein we report a direct cross-coupling of two different aryl halides in the presence of a palladium catalyst and boron ester, which provides a new and useful complementary method to synthesize tricyclic biaryls.

N-Heterocyclic carbene (NHC)-catalysed atom economical construction of 2,3-disubstituted indoles

A novel organocatalytic approach, harnessing the unique reactivities of N-heterocyclic carbenes (NHCs), has been revealed for the construction of indoles. The NHC-catalysed atom economical synthesis of a wide range of 2-substituted indole-3-acetic acid derivatives is displayed. Strategic application of the developed method was demonstrated for a short synthesis of a cyclin-dependent kinase (CDK) inhibitor: paullone.

Access to 2-Arylindoles via Decarboxylative C?C Coupling in Aqueous Medium and to Heteroaryl Carboxylates under Base-Free Conditions using Diaryliodonium Salts

Easily accessible heteroaromatic carboxylic acids and diaryliodonium salts were successfully employed to construct valuable 2-arylindoles and heteroaryl carboxylates in a regioselective fashion. C2-arylated indoles were produced using a Pd-catalyzed decarboxylative strategy in water without any base, oxidant, or ligand. Heteroaryl carboxylates were prepared under metal and base-free conditions. This protocol was successfully utilized to synthesize Paullone, a cyclin-dependent kinase (CDK) inhibitor.

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.

Rhodium(III)-catalyzed arene and alkene C-H bond functionalization leading to indoles and pyrroles

Recently, the rhodium(III)-complex [Cp*RhCl2]2 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C-H bond functionalization event. In the present report, the use of complexes 1 and its dicationic analogue [Cp*Rh(MeCN)3][SbF6]2 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles.