123663-49-0 Usage
Description
In August 2011, China’s State FDA approved Simcere Pharmaceutical
Group’s new drug application for iguratimod (T-614), a disease modifying
anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis
(RA). Preclinical in vivo studies indicated that iguratimod was effective
in an established adjuvant-induced arthritis model (ED40=3.6 mg/kg)
in rats and also efficacious in a type II collagen-induced arthritis model in DBA/1J mice at 30 mg and 100 mg/kg.
Originator
Toyama (Japan)
Uses
Iguratimod acts as an anti-inflammatory agent, used primarily in the treatment of rheumatoid arthritis.
Brand name
Iremod
Clinical Use
Iguratimod, which was discovered by Toyama Pharmaceuticals and jointly co-developed with Eisai in
Japan, was approved by the PMDA (Pharmaceuticals and Medical Devices Agency) of Japan on June 29,
2012 for the treatment of rheumatoid arthritis. This drug was also independently developed by
Simcere Pharmaceutical Group and is marked as Iremod? in China. The drug exhibited inhibitory
effects on granuloma inflammation, and was shown to be efficacious for the prevention of joint
destruction in adjuvant arthritis.
Synthesis
Several synthesis of iguratimod have been published, the
most likely scale synthesis, which does not require chromatographic purification, is described in the scheme.The synthesis began with commercially available 3-nitro-4-chloro anisole (78) which was reacted
with potassium phenoxide (generated from phenol and potassium t-butoxide at 110 oC) to provide the
corresponding nitrophenyl ether which was subsequently reduced and sulfonylated to furnish
sulfonamide 79. Next, this diphenyl ether was subjected to a Friedel-Crafts reaction with
aminoacetonitrile hydrochloride which gave rise to aminomethylacetophenone 80 in 90% yield. This
aminoketone was then formylated with formic trimethylacetic anhydride 81 at room temperature to
afford formamide 82 in 91% yield, and this material was immediately subjected to O-demethylation
conditions with aluminum trichloride and sodium iodide in acetonitrile to give the phenol 83 in 95%
yield. Finally, treatment of the aminomethyl acetophenone phenol 83 with N,N-dimethylformamide
dimethylacetal in DMF at low temperatures furnished iguratimod (XII) in 87% yield.
in vitro
iguratimod inhibited the release of immunoreactive il-1 beta from human monocytic cell line stimulated with lipopolysaccharides (lps) in a dose-dependent manner (0.3-30 μg/ml). northern blotting analysis using lps-stimulated thp-1 cells indicated that the inhibitory effect of iguratimod on il-1 beta production is caused by the suppression of il-1 beta mrna expression [1].
in vivo
administration of iguratimod did not inhibit the tumor growth, but resulted in attenuation of cachexia symptoms. furthermore, iguratimod decreased the serum levels of il-6, and also reduced its gene expression in the tumor tissues. in addition, exogenously administered il-6 nullified the suppressive effect of iguratimod [2].
IC 50
2.0 (hepatocyte-stimulating activities) and 6.6 μg/ml (immunoreactivities) for il-6 release.
references
[1] tanaka k, aikawa y, kawasaki h, asaoka k, inaba t, yoshida c. pharmacological studies on 3-formylamino-7-methylsulfonylamino-6-phenoxy-4h-1-benzopyran-4-one (t-614), a novel antiinflammatory agent. 4th communication: inhibitory effect on the production of interleukin-1 and interleukin-6. j pharmacobiodyn. 1992;15(11):649-55.[2] tanaka k, urata n, mikami m, ogasawara m, matsunaga t, terashima n, suzuki h. effect of iguratimod and other anti-rheumatic drugs on adenocarcinoma colon 26-induced cachexia in mice. inflamm res. 2007;56(1):17-23.[3] hara m, abe t, sugawara s, mizushima y, hoshi k, irimajiri s, hashimoto h, yoshino s, matsui n, nobunaga m. long-term safety study of iguratimod in patients with rheumatoid arthritis. mod rheumatol. 2007;17(1):10-6.
Check Digit Verification of cas no
The CAS Registry Mumber 123663-49-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,3,6,6 and 3 respectively; the second part has 2 digits, 4 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 123663-49:
(8*1)+(7*2)+(6*3)+(5*6)+(4*6)+(3*3)+(2*4)+(1*9)=120
120 % 10 = 0
So 123663-49-0 is a valid CAS Registry Number.
InChI:InChI=1/C17H14N2O6S/c1-26(22,23)19-13-8-15-12(17(21)14(9-24-15)18-10-20)7-16(13)25-11-5-3-2-4-6-11/h2-10,19H,1H3,(H,18,20)
123663-49-0Relevant articles and documents
NOVEL CRYSTAL OF N- 3-(FORMYLAMINO)-4-OXO-6-PHENOXY-4H-CROME NE-7-YL METHANESULFONAMIDE
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Page/Page column 6, (2008/06/13)
The crystal of N-[3-(formylamino)-4-oxo-6-phenoxy-4H-chromen-7-yl]methanesulfonamide having peaks at the positions of 6.00±0.05°, 10.54±0.05°, 17.42±0.08°, 18.39±0.08°, 20.13±0.10° and 23.01±0.10° on 2θ of diffraction angle in powder X-ray diffraction pattern of present invention is low hygroscopic, stable under a high humidity condition, and is useful as a drug substance of excellent anti-inflammatory agent.
Antiangiogenic combination therapy for the treatment of cancer
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, (2008/06/13)
The present invention provides combinations of a DNA topoisomerase I inhibiting agent and a selective COX-2 inhibiting agent for preventing, treating, and/or reducing the risk of developing a neoplasia disorder in a mammal.
4H-1-benzopyran-4-one derivative or its salt, process for producing the same and pharmaceutical composition comprising the same as active ingredient
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, (2008/06/13)
This invention relates to a 4H-1-benzopyran-4-one derivative represented by the formula: STR1 or a salt thereof, a process for producing the same and a pharmaceutical composition comprising the same as active ingredient.