53902-12-8 Usage
Description
Tranilast (53902-12-8) is an anti-allergy agent (inhibitor of mast cell degranulation) that has been shown to have potent immunomodulatory effects via inhibition of endotoxin induced: PGE2, IC50 = 1-20 μM; TXB2, IC50 = 10-50 μM; TGFβ1, IC50 = 100-200 μM; IL-8, IC50 = 100 μM .1-3 Tranilast also displays anti-angiogenic properties.4,5
Chemical Properties
Pale Green Solid
Originator
Rizaben,Kissei Pharmaceutical Co., Ltd.,Japan,1982
Uses
Different sources of media describe the Uses of 53902-12-8 differently. You can refer to the following data:
1. Antiallergic drug, used to treat bronchial asthma, allergic rhinitis and atopic dermatitis.
2. coronary vasodilator
3. Tranilast is a compound that exhibits anti-inflammatory and immunomodulatory effects by inhibiting lipid mediator and cytokine release from inflammatory cells and interfering with PDGF- and TGF-β1-induced proliferation and migration of vascular medial smooth muscle cells. Tranilast suppresses production of prostaglandin D2 (IC50 = 0.1 mM), prostaglandin E2 (IC50 = ~1-20 μM), thromboxane B2 (IC50 = ~10-50 μM), TGF-β1 (IC50 = ~100-200 μM), and interleukin-8 (IC50 = ~100 μM) in in vitro models as well as attenuates of the proinflammatory activity of human monocytes. While originally marketed as an antiallergenic drug, the efficacy of tranilast in preventing restenosis after percutaneous coronary intervention has been tested in a large-scale clinical trial. Additionally, tranilast inhibits VEGF-induced angiogenetic activities (i.e., proliferation, migration and tube formation of vascular endothelial cells) with IC50 values of 22, 18 and 193 μM, which may prove therapeutic for various retinal diseases.[Cayman Chemical]
Definition
ChEBI: An amidobenzoic acid that is anthranilic acid in which one of the anilino hydrogens is replaced by a 3,4-dimethoxycinnamoyl group.
Manufacturing Process
4 g of 3,4-dimethoxycinnamic acid was dissolved in 20 ml of dry pyridine. To
this solution were added under cooling with ice and agitation 2 g of
benzenesulfonyl chloride whereby a red orange precipitate was formed. The
reaction mixture was stirred for about one hour and then 2 g of methyl
anthranilate were added to the mixture under cooling with ice. The mixture
was stirred for 2 hours at room temperature to complete the reaction. After
completion of the reaction, the reaction mixture was concentrated and the
residue was taken up in about 10 ml of chloroform. The solution was washed
first with a 10% aqueous solution of caustic soda, then with a 10% aqueous
solution of hydrochloric acid and finally with water and then distilled to
remove chloroform whereby crystals of N-(3',4'-dimethoxycinnamoyl)-
anthranilic acid methyl ester were obtained.
This product was dissolved in 10 ml of chloroform. To this solution were added
10 ml of a 10% aqueous solution of caustic soda and the mixture was warmed
at 50°C to effect hydrolysis of the ester group. After completion of the
reaction, the organic phase was separated, washed with water and distilled to
remove the solvent whereby 2.1 g (yield: 48%) of the end product, i.e., N-
(3',4'-dimethoxycinnamoyl)-anthranilic acid, were obtained. This product had a melting point of 211°C to 213°C
Biological Activity
Antiallergic via inhibition of chemical mediator release from mast cells. Most recently shown to be an effective inhibitor of angiogenesis. Demonstrated to antagonize the effects of angiotensin II on human arteries, possibly by an interaction at the level of the AT 1 receptor.
Biochem/physiol Actions
Tranilast also inhibits vascular smooth muscle cell proliferation by inhibiting the cyclin-dependent kinase inhibitor-1(p21Waf1/Cip1) and may be useful in treating cardiac allograft vasculopathy. It is used in treating hypertrophic scars and keloids. Tranilast inhibits tumor necrosis factor (TNF-α and TGF-β2), obstructing epithelial-mesenchymal transition in human retinal pigment epithelial cell line (ARPE).
References
1) Capper et al. (2000) Modulation of human monocyte activities by tranilast, SB252218, a compound demonstrating efficacy in restenosis; J. Pharmacol. Exp. Ther., 38 2673
2) Ward et al., (2002) Tranilast prevents activation of transforming growth factor-b system, leukocyte accumulation and neointimal growth in porcine coronary arteries after stenting; Arterioscler. Thromb. Vasc. Biol., 22 940
3) Chikaraishi et al. (2001) Tranilast inhibits interleukin-1b-induced monocyte chemoattractant protein-1 expression in rat mesangial cells; Eur. J. Pharmacol., 427 151
4) Isaji et al. (1997) Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo; Br. J. Pharmacol., 122 1061
5) Koyama et al. (1999) Tranilast inhibits protein kinase C-dependent signaling pathway linked to angiogenic activities and gene expression of retinal microcapillary endothelial cells; Br. J. Pharmacol., 127 537
Check Digit Verification of cas no
The CAS Registry Mumber 53902-12-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,3,9,0 and 2 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 53902-12:
(7*5)+(6*3)+(5*9)+(4*0)+(3*2)+(2*1)+(1*2)=108
108 % 10 = 8
So 53902-12-8 is a valid CAS Registry Number.
InChI:InChI=1/C18H17NO5/c1-23-15-9-7-12(11-16(15)24-2)8-10-17(20)19-14-6-4-3-5-13(14)18(21)22/h3-11H,1-2H3,(H,19,20)(H,21,22)/b10-8+
53902-12-8Relevant articles and documents
N-Cinnamoylanthranilates as human TRPA1 modulators: Structure-activity relationships and channel binding sites
Chandrabalan, Arundhasa,McPhillie, Martin J.,Morice, Alyn H.,Boa, Andrew N.,Sadofsky, Laura R.
supporting information, p. 141 - 156 (2019/03/17)
The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel, which detects noxious stimuli leading to pain, itch and cough. However, the mechanism(s) of channel modulation by many of the known, non-reactive modulators has not been fully elucidated. N-Cinnamoylanthranilic acid derivatives (CADs) contain structural elements from the TRPA1 modulators cinnamaldehyde and flufenamic acid, so it was hypothesized that specific modulators could be found amongst them and more could be learnt about modulation of TRPA1 with these compounds. A series of CADs was therefore screened for agonism and antagonism in HEK293 cells stably transfected with WT-human (h)TRPA1, or C621A, F909A or F944A mutant hTRPA1. Derivatives with electron-withdrawing and/or electron-donating substituents were found to possess different activities. CADs with inductive electron-withdrawing groups were agonists with desensitising effects, and CADs with electron-donating groups were either partial agonists or antagonists. Site-directed mutagenesis revealed that the CADs do not undergo conjugate addition reaction with TRPA1, and that F944 is a key residue involved in the non-covalent modulation of TRPA1 by CADs, as well as many other structurally distinct non-reactive TRPA1 ligands already reported.
