188817-13-2

Usage

Uses

Used in Pharmaceutical Research:
SC-560 is used as a cyclooxygenase-1 (COX-1) inhibitor for studying its effects on prostaglandin E-2 (PGE2) signaling in ciliogenesis in zebrafish embryos. This application helps researchers understand the role of COX-1 in the development of cilia and its potential implications in various diseases.
Used in Toxicological Studies:
SC-560 is used as a selective inhibitor of COX-1 to study its role in PM10-induced endothelial dysfunction. This application aids in understanding the impact of air pollution on vascular health and the potential protective role of COX-1 inhibition in such scenarios.
Used in Angiogenesis and Apoptosis Research:
SC-560 is used as a cyclooxygenase inhibitor to study its effects on angiogenesis and apoptosis. This application is crucial for understanding the role of COX-1 in the regulation of blood vessel formation and cell death, which are important processes in various pathological conditions, including cancer and inflammatory diseases.

Biological Activity

Highly selective cyclooxygenase-1 (COX-1) inhibitor (IC 50 values are 0.009 and 6.3 μ M for COX-1 and COX-2 respectively). Inhibits COX-1-derived platelet thromboxane B 2 , gastric PGE 2 and dermal PDE 2 production. Significantly reduces ovarian surface epithelial tumor growth in vivo . Orally active.

Biochem/physiol Actions

SC-560 (5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole) is a non-steroidal anti-inflammatory drug (NSAID). It is a lipophilic, diaryl heterocyclic compound. SC-560 acts as an effective antiviral agent against hepatitis C virus (HCV). It also has a potential to hinder prostaglandin E2 synthesis in neurons at nanomolar concentrations.

in vitro

preincubation of cox-1 with sc-560 inhibited the conversion of arachidonic acid to pge2 in a concentration-dependent manner [1]. sc-560 was necessary to sustain a reduced basal level of pgi2 for an extended period. sc-560 inhibits cell proliferation and accelerates apoptosis which results in attenuated tumor growth [2].

in vivo

oral dosing with either 10 or 30 mg/kg sc-560 1 hr before assay completely inhibited cox-1-derived platelet thromboxane b2, gastric pge2, and dermal pge2 production [1]. sc-560 can suppress ovarian surface epithelial tumor growth. tumor growth was suppressed in allografted mice treated with sc-560 for a longer period, but the reduction in tumor growth was less dramatic than the short-term treated [2].

IC 50

0.009 μm for cox-1; 6.3 μm for cox-2

references

[1] daikoku t, wang d, tranguch s, morrow jd, orsulic s, dubois rn, dey sk. cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer. cancer res. 2005 may 1;65(9):3735-44.[2] christopher j. smith, yan zhang, carol m. koboldt, jerry muhammad, ben s. zweifel, alex shaffer, john j. talley, jaime l. masferrer, karen seibert, peter c. isakson. pharmacological analysis of cyclooxygenase-1 in inflammation. proc natl acad sci u s a. 1998 oct 27; 95(22): 13313–13318.

InChI:InChI=1/C17H12ClF3N2O/c1-24-14-8-6-13(7-9-14)23-15(10-16(22-23)17(19,20)21)11-2-4-12(18)5-3-11/h2-10H,1H3

Upstream product

• 77063-21-9 4-(4-chlorophenyl)-1,1,1-trifluorobut-3-yn-2-one 
• 3471-32-7 4-Methoxyphenylhydrazine 
• 696-62-8 para-iodoanisole 
• 142623-90-3 5-(4-chloridophenyl)-3-(trifluoridomethyl)-1H-pyrazole 
• 873-73-4 4-n-chlorophenylacetylene 
• 99-91-2 para-chloroacetophenone 
• 19501-58-7 4-methoxyphenylhydrazine hydrochloride 
• 18931-60-7 1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-dione 
• 1610846-19-9 ((1-(4-chlorophenyl)vinyl)oxy)triethylsilane 
• 116853-79-3 trifluoroacetaldehyde 4-methoxyphenylhydrazone 

Relevant academic research and scientific papers

Palladium-Catalyzed Methylation of Aryl, Heteroaryl, and Vinyl Boronate Esters

A method for the direct methylation of aryl, heteroaryl, and vinyl boronate esters is reported, involving the reaction of iodomethane with aryl-, heteroaryl-, and vinylboronate esters catalyzed by palladium and PtBu2Me. This transformation occurs with a remarkably broad scope and is suitable for late-stage derivatization of biologically active compounds via the boronate esters. The unique capabilities of this method are demonstrated by combining carbon-boron bond-forming reactions with palladium-catalyzed methylation in a tandem transformation.

Mild and Regioselective Synthesis of 3-CF3-Pyrazoles by the AgOTf-Catalysed Reaction of CF3-Ynones with Hydrazines

Gold- and silver-catalysed reactions of trifluoromethylated ynones with aryl (alkyl) hydrazines were investigated. The use of (THD-Dipp)AuOTf and AgOTf resulted in quick heterocyclization reactions to selectively give 3-CF3-pyrazoles. AgOTf was found to be the catalyst of choice, and various 3-CF3-pyrazoles were formed in up to 99 % isolated yield with high regioselectivity. The reaction has a broad scope: 3-CF3-pyrazoles with alkyl and aryl substituents as well as different functional groups can be prepared by this approach. The known pyrazole drugs Celebrex and SC-560 were efficiently prepared to demonstrate the utility of the method. Mechanistic investigations revealed that the reaction involves the formation of a hemiaminal as a key intermediate.

Polysubstituted 3-trifluoromethylpyrazoles: Regioselective (3 + 2)-cycloaddition of trifluoroacetonitrile imines with enol ethers and functional group transformations

Non-catalysed addition of trifluoroacetonitrile imines to enol ethers provided fully regioselectively (3 + 2)-cycloadducts, which either spontaneously or via Br?nsted acid-induced elimination of ROH molecules led to the formation of 3-trifluoromethylated

Synthesis of Celecoxib, Mavacoxib, SC-560, Fluxapyroxad, and Bixafen Enabled by Continuous Flow Reaction Modules

Multi-step continuous flow synthesis enables a parallel approach to obtain agrochemicals and pharmaceuticals containing 3-fluoroalkyl pyrazole cores. In this system, fluorinated amines are transformed into pyrazole cores through a telescoped in situ generation and consumption of diazoalkanes. Once synthesized, additional continuous flow and batch reactions add complexity to the pyrazole core via C–N arylation and methylation, TMS cleavage, and amidation. Using this modular assembly line approach, Bixafen and Fluxapyroxad were synthesized in 38 % yield over four continuous flow steps in an overall reaction time of 56 min. Finally, coupling selected continuous flow processes with an offline (batch) Ullmann coupling afforded Celecoxib, Mavacoxib, and SC-560 in 33–54 % yield over two to three steps.

Selective, Metal-Free Approach to 3- or 5-CF3-Pyrazoles: Solvent Switchable Reaction of CF3-Ynones with Hydrazines

A detailed study of the reaction of trifluoroacetylated acetylenes and aryl (alkyl) hydrazines was performed, aimed to the regioselective synthesis of 3- or 5-trifluoromethylated pyrazoles. It was found that the regioselectivity of reaction depends dramatically on the solvent nature. Highly polar protic solvents (hexafluoroisopropanol) favor the formation of 3-trifluoromethylpyrazoles. In contrast, when the reaction was performed in polar aprotic solvents (DMSO), the formation of their 5-CF3-substituted isomers was preferentially observed. Alternatively, the regioselective assembly of 3-CF3-substituted pyrazoles can be performed via two-step one-pot procedure. The reaction of trifluoromethylated ynones with aryl (alkyl) hydrazines in the presence of acidic catalysts leads to formation of the corresponding hydrazones. The latter can be smoothly transformed into 3-CF3-pyrazoles by treatment with a base. This solvent-switchable procedure was used for the preparation of such important drugs as Celebrex and SC-560 as well as their isomers in gram scale. The possible reaction mechanism is discussed.

Methods of treating or preventing a cardiovascular condition using a cyclooxygenase-1 inhibitor

Methods for treating or preventing one or more cardiovascular conditions in a subject comprising treating the subject with a therapeutically effective amount of a selective cyclooxygenase-1 inhibitor or a pharmaceutically-acceptable salt, tautomer or prod

Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)- 3(trifluoromethyl)-1h-pyrazol-1-yl]benzenesulfonamide (sc-58635, celecoxib)

A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC- 236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-y1]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.