64920-21-4

Upstream product

• 605-62-9 4-nitro-1-naphthol 
• 86-57-7 1-Nitronaphthalene 
• 2834-90-4 4-amino-1-naphthol 
• 98-59-9 p-toluenesulfonyl chloride 
• 236739-37-0 N-(2,3-dibromo-4-oxo-3,4-dihydro-2H-naphthalen-1-ylidene)-4-methyl-benzenesulfonamide 

Downstream Products

• 36062-30-3 N-p-tolylsulfonyl-1,4-naphthoquinone-4-imine 
• 139739-77-8 4-p-tolylsulfonylimino-2,2,3,3-tetrachloro-1,2,3,4-tetrahydronaphthalen-1-one 
• 124052-35-3 N-p-tolylsulfonyl-2-chloro-1,4-aminonaphthol 
• 117-80-6 2,3-Dichloro-1,4-naphthoquinone 
• 152509-81-4 N-p-methylbenzenesulfonyl-2-bromo-1,4-naphthoquinone imine 
• 146463-29-8 N-(3-bromo-4-hydroxynaphthalen-1-yl)-4-methylbenzenesulfonamide 
• 139719-08-7 2,3-Dichloro-N-p-tolylsulfonyl-1,4-naphthoquinonemonoimine 
• 70249-49-9 N-(3-chloro-4-oxonaphthalen-1(4H)-ylidene)-4-methyl benzenesulfonamide 

Relevant academic research and scientific papers

Inhibition of mutated isocitrate dehydrogenase 1 in cancer

Background: R132H mutation of isocitrate dehydrogenase 1 (IDH1) is found in ~75% of low-grade gliomas and secondary glioblastomas as well as in several other types of cancer. More chemotypes of inhibitors of IDH1(R132H) are therefore needed. Objective: The study aimed to develop a new class of IDH1(R132H) inhibitors as potent antitumor agents. Method: A biochemical assay was developed to find inhibitors of IDH1(R132H) mutant enzyme. Chemical synthesis and structure-activity relationship studies were used to find compounds with improved potency. Antitumor activities of selected compounds were evaluated. Results: A series of aromatic sulfonamide compounds was found to be novel, potent inhibitors of IDH1(R132H) with Ki values as low as 0.6 μM. Structure-activity relationships of these compounds are discussed. Enzyme kinetics studies showed that one compound is a competitive inhibitor against the substrate α-KG and a non-competitive inhibitor against the cofactor NADPH. Several inhibitors were found to have no activity against wild-type IDH1, showing a high selectivity. Two potent inhibitors exhibited strong activity against proliferation of BT142 glioma cells with IDH1 R132H mutation, while these compounds did not significantly affect the growth of glioma cells without IDH1 mutation. Conclusion: This novel series of IDH1(R132H) inhibitors have potential to be further developed for the treatment of glioma with IDH1 mutation.

The relevance of Ki calculation for bi-substrate enzymes illustrated by kinetic evaluation of a novel lysine (K) acetyltransferase 8 inhibitor

Histone acetyltransferases (HATs) are important mediators of epigenetic post-translational modifications of histones that play important roles in health and disease. A disturbance of these modifications can result in disease states, such as cancer or inflammatory diseases. Inhibitors of HATs (HATi) such as lysine (K) acetyltransferase 8 (KAT8), could be used to study the epigenetic processes in diseases related to these enzymes or to investigate HATs as therapeutic targets. However, the development of HATi is challenged by the difficulties in kinetic characterization of HAT enzymes and their inhibitors to enable calculation of a reproducible inhibitory potency. In this study, a fragment screening approach was used, enabling identification of 4-amino-1-naphthol, which potently inhibited KAT8. The inhibitor was investigated for enzyme inhibition using kinetic and calorimetric binding studies. This allowed for calculation of the Ki values for both the free enzyme as well as the acetylated intermediate. Importantly, it revealed a striking difference in binding affinity between the acetylated enzyme and the free enzyme, which could not be revealed by the IC50 value. This shows that kinetic characterization of inhibitors and calculation of Ki values is crucial for determining the binding constants of HAT inhibitors. We anticipate that more comprehensive characterization of enzyme inhibition, as described here, is needed to advance the field of HAT inhibitors.

Potential therapeutic application of small molecule with sulfonamide for chondrogenic differentiation and articular cartilage repair

The restoration of damaged articular cartilage is a long-pursued goal in regenerative medicine. Chondrocyte-specific differentiation of mesenchymal stem cells (MSCs) may be an effective means of repairing damaged cartilage. We identified small molecule 6

Use of compounds for inducing differentiation of mesenchymal stem cells to chondrocytes

Use of a compound of Formula 1 for inducing differentiation of mesenchymal stem cells to chondrocytes, and a pharmaceutical composition for treating a cartilage disease, which includes chondrocytes in which differentiation from mesenchymal stem cells is induced by the compound of Formula 1, are provided. Differentiation of the mesenchymal stem cells treated with the compound of Formula 1 to chondrocytes is specifically induced, and thus the compound can be used to effectively treat a cartilage disease such as arthritis, cartilage damage, and a cartilage defect.

Discovery of N-(3-((7H-purin-6-yl)thio)-4-hydroxynaphthalen-1-yl)- sulfonamide derivatives as novel protein kinase and angiogenesis inhibitors for the treatment of cancer: Synthesis and biological evaluation. Part III

A novel series of N-(3-((7H-purin-6-yl)thio)-4-hydroxynaphthalen-1-yl)- sulfonamides were designed and synthesized. Biological characterization revealed that several compounds exerted enhanced anti-proliferative activity against human umbilical vein endothelial cells (HUVECs) and several cancer cell lines and high specific protein kinase and angiogenesis inhibitory activities. Compared with our previously synthesized compounds, the substitution of sulfonamide structure for amide fragment played an essential role for the advance of inhibitory activities. In addition, the replacement of 1H-1,2,4-triazole ring by 7H-purine did not result in obvious decrease of inhibition efficacy, indicating that the sulfonamide structure contributes even more to the inhibition efficacy than the 1H-1,2,4-triazole ring. Among these compounds, compound 9n demonstrated comparable in vitro antiangiogenic activities to pazopanib in both HUVEC tube formation assay and the rat thoracic aorta rings (TARs) test. Meanwhile, compound 9n was identified to inhibit Akt1 (IC50 = 1.73 μM) and Abl tyrosine kinase (IC50 = 1.53 μM) effectively.

USE OF A COMPOUND FOR INDUCING DIFFERENTIATION OF MESENCHYMAL STEM CELLS INTO CARTILAGE CELLS

Use of a compound of Formula 1 for inducing differentiation of mesenchymal stem cells to chondrocytes, and a pharmaceutical composition for treating a cartilage disease, which includes chondrocytes in which differentiation from mesenchymal stem cells is induced by the compound of Formula 1, are provided. Differentiation of the mesenchymal stem cells treated with the compound of Formula 1 to chondrocytes is specifically induced, and thus the compound can be used to effectively treat a cartilage disease such as arthritis, cartilage damage, and a cartilage defect.

Some reactions of new semiquinoid compounds derived from N-arylsulfonyl-p-quinonimines

Polyhalogenated semiquinoid compounds on the basis of N-arylsulfonyl-p-quinonimines react with reducing agents (zinc or sodium dithionite in acetic acid) with elimination of one or two hydrogen halide molecules, depending on the number of hydrogens at the sp3-hybridized carbon atoms, to give the corresponding benzoid structures. Dehydrohalogenation of the title compounds in chloroform in the presence of triethylamine leads to formation of quinonimines. N,N′-Bis(arylsulfonyl)-p-quinonediimine derivatives do not undergo dehydrohalogenation. Reactions with dialkyl hydrogen phosphites result mostly in 1,2-addition and formation of phosphorylated products; the reaction is likely to involve intermediate dehydrohalogenation to the corresponding quinonimines which can be isolated in the pure state.