129-56-6

Usage

Uses

Used in Cellular Research:
1,9-Pyrazoloanthrone is used as a broad-spectrum serine/threonine kinase inhibitor of JNK for testing the stimulation of myogenesis in C2C12 myoblasts and the effects on oxysterol-induced necrosis in HepG2 cells.
Used in Pharmaceutical Applications:
1,9-Pyrazoloanthrone is used as a Jun N-terminal kinase (JNK) inhibitor for its anti-inflammatory activity and its ability to inhibit the expression of presenilin-1 and Notch signaling in mouse brain.
Used in Enzyme Inhibition Studies:
1,9-Pyrazoloanthrone is used as a potent inhibitor of c-Jun N-terminal kinase (JNK) to block the phosphorylation of c-Jun and the expression of IL-2, IFN-γ, TNF-α, and COX-2 in cells. It also blocks IL-1-induced accumulation of phospho-Jun and the induction of c-Jun transcription.
Used in Drug Development:
1,9-Pyrazoloanthrone is used as a lead compound in the development of novel drug delivery systems to enhance its applications and efficacy against various diseases, particularly in the context of cancer research and treatment.

Biological Activity

Selective inhibitor of c-Jun N-terminal kinase (JNK). Competitively and reversibly inhibits JNK1, 2 and 3 (IC 50 = 40-90 nM) with negligible activity at ERK2, p38 β and a range of enzymes (IC 50 > 10 μ M). Active in vivo . Shown to have reduced selectivity over other protein kinases under certain conditions. Protects renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis. Also available as part of the MAPK Inhibitor Tocriset? .

Biochem/physiol Actions

SP600125 is an anthrapyrazolone inhibitor of JNK that competes with ATP to inhibit the phosphorylation of c-Jun. It prevents the activation of inflammatory genes such as COX-2, IL-2 IFN-γ and TNF-α.8,9 It prevents the activation of JNK after brain ischemia and may be effective in treatment of ischemic stroke.10

Safety Profile

Poison by intravenous route.When heated to decomposition it emits toxic fumes ofNOx.

References

1)Bennett et al. (2001), SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase; Proc. Natl. Acad. Sci. USA., 98 13681 2) Rahman et al. (2012), Intraperitoneal injection of JNK-specific inhibitor SP600125 inhibits the expression of presenilin-1 and Notch signaling in mouse brain without induction of apoptosis; Brain Res., 1448 117

InChI:InChI=1/C14H8N2O/c17-14-9-5-2-1-4-8(9)13-12-10(14)6-3-7-11(12)15-16-13/h1-7H,(H,15,16)

Upstream product

• 82-44-0 1-chloroanthracene-9,10-dione 
• 54345-84-5 2-acetyl-2H-dibenzo[cd,g]indazol-6-one 
• 82-45-1 1-amino-9,10-anthracenedione 
• 83132-67-6 Ethyl 9,10-anthraquinon-1-ylhydrazonocyanacetylcarbamate 

Downstream Products

• 163359-08-8 1-methylanthra[1,9-cd]pyrazol-6(1H)-one 
• 54642-23-8 JNK Inhibitor II, Negative Control 

Relevant academic research and scientific papers

Structural and biological evaluation of halogen derivatives of 1,9-pyrazoloanthrones towards the design of a specific potent inhibitor of c-Jun-N-terminal kinase (JNK)

c-Jun N-terminal kinase (JNK), a member of the MAPK family, is associated with a variety of diseases and immune responses. To dissect the mechanistic role of JNKs in such processes, a specific inhibitor for JNKs holds great value. SP600125 is a widely used inhibitor of JNKs despite its non-specific activity. In an effort to obtain better specific inhibitors, three anthrapyrazolone halogenated derivatives have been synthesized and characterized. Among the three derivatives, 5-chloro-2-(2-chloroethyl)dibenzo[cd,g] indazol-6(2H)-one is clearly established as a specific inhibitor of JNK with augmented expression of chemokines in LPS-activated macrophages based on modelling studies followed by in vitro and ex vivo evaluation.

New Colorimetric and Fluorometric Fluoride Ion Probe Based on Anthra[1,9-cd]pyrazol-6(2H)-one

New colorimetric and fluorometric fluoride ion probe, anthra[1,9-cd]pyrazol- 6(2H)-one (1), was synthesized by one-step condensation. The probe 1 shows F?-selective color change from colorless to pink and appearance of red fluorescence. The flu

Method for producing pyrazolanthone by using 1 - aminoanthraquinone (by machine translation)

The invention discloses a method for producing pyrazolanthone by using 1 - aminoanthraquinone, and belongs to the technical field of chemical engineering. The method comprises the following steps: (1) adding sulfuric acid in the reaction kettle, adding 65 - 70 °C aminoanthraquinone to the reaction kettle, warming up to 2 - 3h, heating the material into a reduction kettle; (1 -) adding sulfuric acid to the reaction kettle; and (2) carrying out cyclization reaction in a time-sharing stage reaction mode to obtain the pyrazolanthrapyone after the reaction is finished to 5 - 10 °C 3, adding the sodium nitrite solution to the reaction kettle after the reaction is finished 4 - 5h. The preparation method is higher in product yield and higher in purity, and can be well applied to dye production. (by machine translation)

Methods for treating inflammatory conditions or inhibiting JNK

This invention generally relates to methods for treating or preventing an inflammatory disease or disorder comprising administering to a patient in need thereof an effective amount of a Pyrazoloanthrone Derivative having the following structure: or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are as defined herein.

EDC-mediated condensations of 1-chloro-5-hydrazino-9,10-anthracenedione, 1-hydrazino-9,10-anthracenedione, and the corresponding anthrapyrazoles

The EDC-mediated condensation of 1-chloro-5-hydrazino-9,10-anthracenedione afforded an N-1 acyl anthrapyrazole instead of the expected hydrazide. The regiochemistry of the N-acyl substituent was assigned on the basis of an extensive set of NMR experiments, and identification of this isomer suggests a reaction sequence based on initial acylation and subsequent cyclization. In contrast, the parallel reaction of 1-hydrazino-9,10-anthracenedione proceeded to afford the expected hydrazide.

Design, synthesis, and anticancer properties of 4,4′ -dihydroxybenzophenone-2,4-dinitrophenylhydrazone and analogues

4,4′-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals of this study were to modify A-007's chemical moieties with the ultimate goal of maximizing its anticancer activity through increased planarity and introduction of functional groups. Thirty-five phenylhydrazone analogues of A-007 were synthesized and evaluated in vitro in a human primary cancer explant assay. Anticancer activities for selected analogues were also assayed for activity vs established human/murine cell lines. One-hundred-eighty-six fresh human solid tumors were used to screen for anticancer activity. Selected analogues were assayed for therapeutic indices (vs GM-CFC from bone marrow) in preparation for preclinical studies. Several polyaryl phenylhydrazones demonstrated improved cytotoxic activities by factors of 102-103 when compared with A-007. However, the polyaryl quinone moieties of the latter analogues introduced potential toxic properties (cardiac, hematological) that do not exist with A-007.

CYCLIZATION REACTIONS OF SOME o-ACYLPHENYLHYDRAZONES

The hydrazones Ia-Id and IIa-IId have been prepared by azo coupling of ethyl cyanacetylcarbamate and cyanacetamide, respectively, with diazotized o-aminoacetophenone, o-aminobenzophenone, 2-(2-aminobenzoyl)benzoic acid and 1-amino-9,10-antraquinone.The hydrazones Ia-Id have been alkaline or thermally cyclized to 2-aryl-4,5-dioxo-2,3,4,5-tetrahydro-1,2,4-triazine-6-carbonitriles IIIa-IIId.On boiling in strongly acidic medium the hydrazones I and II are cyclized to the corresponding 3-substituted indazoles Va-Vc and 2,6-dihydronaphthoindazol-6-one (Vd).Three hours boiling in 20percent hydrochloric acid does not affect the 1,2,4-triazine cycle of nitriles IIIa-IIId, the nitrile groups being only hydrolyzed to give the corresponding carboxylic acids IVa-IVd.On contrary, boiling in aqueous pyridine causes splitting of the 1,2,4-triazine cycle and formation of arylhydrazonocyanacetamides IIa-IId.IR and NMR spectroscopy has been used to study the possibility of simultaneous hydrogen bond to the both carbonyl groups in hydrazones I and II.