123663-49-0 Usage
Uses
Used in Pharmaceutical Industry:
Iguratimod is used as an anti-inflammatory agent for the treatment of rheumatoid arthritis. It helps in managing the symptoms and progression of the disease by reducing inflammation and joint damage.
Used in Rheumatology:
Iguratimod is used as a disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis patients. It is effective in reducing the severity of the disease and improving the quality of life for those suffering from RA.
Originator
Toyama (Japan)
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.
Method for the treatment and prevention of cachexia
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, (2008/06/13)
Cachexia, including anorexia and other forms of weight loss, is a frequent complication of acute and chronic infections, and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. The present invention includes methods for the treatment or prevention of cachexic conditions while maintaining the production of factors essential for infection control through the administration of an effective amount of a cyclooxygenase-2 selective inhibiting compound.
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.
Synthesis and antiinflammatory activity of 7-methanesulfonylamino-6- phenoxychromones. Antiarthritic effect of the 3-formylamino compound (T-614) in chronic inflammatory disease models
Inaba, Takihiro,Tanaka, Keiichi,Takeno, Ryuko,Nagaki, Hideyoshi,Yoshida, Chosaku,Takano, Shuntaro
, p. 131 - 139 (2007/10/03)
A group of derivatives of 7-methanesulfonylamino-6-phenoxychromone (1) at the pyrone and phenoxy rings was synthesized starting with 4-chloro-3- nitroanisole and evaluated against acute and chronic inflammations in oral administration in animals. Significant potency in the rat models of carrageenin-induced edema (CPE) and adjuvant-induced arthritis (AA) was realized with 2'-fluoro and 2',4'-difluoro derivatives (9a and 9d), and 3- formylamino derivative (19a) and its 2'-fluoro and 2',4'-difluoro compounds (22a and 22d), displaying AA therapeutic effect of ED40=2.5-7.1 mg/kg/d for 7 d and AA prophylactic effect of 53-70% inhibition at the dosage of 3 mg/kg/d for 22 d. To identify a candidate for further pharmacological study, the five compounds were subjected to evaluation of their gastro-ulcerogenic liability, leading to selection of the fluorine-free compound 19a which did not cause acute ulceration at 300 mg/kg in oral administration in rats. Compound 19a (ED40=3.6 mg/kg in established AA) possessed good therapeutic efficacy against type II collagen-induced arthritis in DBA/1J mice with doses of 30 and 100 mg/kg, suggesting the development of 19a (designated T-614) as a prospective disease-modifying antirheumatic agent. In addition, a preparative-scale synthetic route to T-614 has been established.
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.
