94055-76-2

Usage

Uses

Used in Pharmaceutical Industry:
Suplatast tosilate is used as an antiallergic drug for the treatment of bronchial asthma, atopic dermatitis, and allergic rhinitis. It inhibits antigen-induced histamine release from mast cells, as well as IgE antibody formation, and suppresses interleukin (IL)-4 release from T cells. In human peripheral basophils, suplatast tosilate inhibits the antigen-induced release of IL-13 but not IL-4.
Used in Asthma Treatment:
Suplatast tosilate is used as a novel capsular anti-asthmatic agent that suppresses both IgE production and IL-4 and IL-5 synthesis with an IC50 above 100 μM. It inhibits IL-4 and IL-5 production in conalbumin-stimulated D10.G4.1 murine T helper 2 (Th2) cells in a concentration-dependent manner.
Used in Allergic Rhinitis and Atopic Dermatitis Treatment:
Suplatast tosilate is used to improve clinical symptoms in allergic patients, which correlates with a significant decrease in serum IgE antibody levels. It also inhibits ovalbumin-induced increases in eosinophil and total cell numbers, as well as IL-4, IL-5, and IL-13 levels in bronchoalveolar lavage fluid (BALF) in an ovalbumin-sensitized mouse model of asthma. Additionally, it inhibits ovalbumin-induced increases in ovalbumin-specific IgE in serum and bronchial hyperresponsiveness to methacholine in the ovalbumin-sensitized mouse model of asthma.

Biological Activity

Th2 cytokine inhibitor that attenuates IL-2, IL-5 and IL-13 production and has no effect on IFN- γ production. Acts as an immunoregulator that suppresses IgE production, eosinophil infiltration and histamine release. Exhibits antiasthmatic, anti-inflammatory and antifibrotic activity in vivo and is orally active.

References

1) Kurokawa?et al.?(2001),?Suppressive effects of anti-allergic agent suplatast tosilate (IPD-1151T) on the expression of co-stimulatory molecules on mouse splenocytes in vivo; Mediators Inflamm.,?10?333 2) Hsu?et al.?(2007),?The effects of suplatast tosilate (IPD-1151T) on innate immunity and antigen-presenting cells; Transpl. Immunol.,?18?108 3) Furonaka?et al.?(2009),?Suplatast tosilate prevents bleomycin-induced pulmonary fibrosis in mice; Curr. Opin. J. Pharmacol. Exp. Ther.,?328?55 4) Bhattachrya?et al.?(2014),?Simultaneous inhibition of T helper 2 and T regulatory cell differentiation by small molecules enhances Bacillus Calmette-Guerin vaccine efficacy against tuberculosis; J. Biol. Chem.,?289?33404 5) Wada?et al.?(2009),?Effect of suplatast tosilate on antileukotriene non-responders with mild-to-moderate persistent asthma; Allergol. Int.,?58?389

InChI:InChI=1/C16H25NO4S.C7H8O3S/c1-4-20-11-14(18)12-21-15-7-5-13(6-8-15)17-16(19)9-10-22(2)3;1-6-2-4-7(5-3-6)11(8,9)10/h5-8,14,18H,4,9-12H2,1-3H3;2-5H,1H3,(H,8,9,10)

Upstream product

• 80-48-8 methyl p-toluene sulfonate 
• 160114-16-9 2-{4-(3-ethoxy-2-hydroxypropoxy)phenylcarbamoyl}ethyl methyl sulfide 
• 123-30-8 4-amino-phenol 
• 100-02-7 4-nitro-phenol 
• 94925-71-0 1-Ethoxy-3-(4-nitro-phenoxy)-propan-2-ol 
• 94056-98-1 4-[3-ethoxy-2-(hydroxy)propoxy]aniline 
• 125228-75-3 4-nitrophenyl 2-oxiranylmethyl ether 

Relevant academic research and scientific papers

Four new polymorphic forms of suplatast tosilate

We found four new polymorphic forms (γ-, E?-, ζ-, and η-forms) of suplatast tosilate (ST) by recrystallization and seeding with ST-analogous compounds; three polymorphic forms (α-, β-, and δ-forms) of ST have been previously reported. The physicochemical properties of these new forms were investigated using infrared (IR) spectroscopy, solid-state nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry. The presence of hydrogen bonds in the new forms was assessed from the IR and solid-state NMR spectra. The crystal structures of the E?- and η-forms were determined from their powder X-ray diffraction data using the direct space approach and the Monte Carlo method, followed by Rietveld refinement. The structures determined for the E?- and η-forms supported the presence of hydrogen bonds between the ST molecules, as the IR and solid-state NMR spectra indicated. The thermodynamic characteristics of the seven polymorphic forms were evaluated by determining the solubility of each form. The α-form was the most insoluble in 2-propanol at 35 C, and was thus concluded to be the most stable form. The E?-form was the most soluble, and a polymorphic transition from the E?- to the α-form was observed during solubility testing.

Preparation method of metasulfonate

The invention discloses a preparation method of metasulfonate. According to the preparation method, a compound (5) is used as an initial raw material, a compound 1 is prepared through a condensation reaction with a compound (6) in the presence of a condensing agent, the raw materials are easy to obtain, post-treatment is simple, reaction steps are reduced, the yield is high, the quality is good, and the cost is low.

Preparation methods of suplatast tosilate and intermediates

The invention relates to preparation methods of suplatast tosilate and intermediates thereof. According to the method, 4-aminophenol is taken as an initial material, and a target compound is obtainedthrough steps of amidation, addition of epichlorohydrin, ring opening and the like. The method avoids a palladium-carbon catalytic hydrogenation step, comprises a short synthesis route and is high inyield, simple to operate and suitable for industrial application. The invention also provides novel intermediates for preparation of suplatast tosilate and preparation methods of the novel intermediates.

Synthesis and antiallergic activity of dimethyl-2- (phenylcarbamoyl)ethylsulfonium p-toluenesulfonate derivatives

The derivatives of dimethyl-2-(phenylcarbamoyl)ethylsulfonium p- toluenesulfonates were synthesized and evaluated for antiallergic activity. The 2,3-dihydroxyethoxy group was introduced to the phenyl ring from the standpoint of lipophilicity and electronic effects of substituent. The IgE- induced rat passive cutaneous anaphylaxis (PCA) was inhibited by oral administration of several substituted 2-[(4- propoxyphenyl)carbamoyl]ethyldimethylsulfonium p-toluenesulfonate derivatives. Among them (±)-2-[N-[4-(3-ethoxy-2- hydroxypropoxy)phenyl]carbamoyl]ethyldimethylsulfonium p-toluenesulfonate (1a, IPD-1151T) was found to possess considerable activity in the PCA test, and it was launched as Suplatast tosilate in Japan.