Ramatroban

Base Information

• Chemical Name: Ramatroban
• CAS No.: 116649-85-5
• Molecular Formula: C21H21FN2O4S
• Molecular Weight: 416.473
• European Community (EC) Number: 631-428-1
• UNII: P1ALI72U6C
• DSSTox Substance ID: DTXSID1046685
• Nikkaji Number: J388.276D
• Wikipedia: Ramatroban
• Wikidata: Q10357327
• NCI Thesaurus Code: C76400
• Pharos Ligand ID: L3NZTPGDT66P
• Metabolomics Workbench ID: 153912
• ChEMBL ID: CHEMBL361812
• Mol file: 116649-85-5.mol

Synonyms:3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-carbazole propanoic acid;BAY u 3405;BAY u 3406;BAY u-3405;BAY u3405;ramatroban

Chemical Property of Ramatroban

Chemical Property:

• Appearance/Colour: Crystalline solid.
• Vapor Pressure: 4.94E-18mmHg at 25°C
• Melting Point: 134-135°
• Refractive Index: 1.664
• Boiling Point: 654.7 °C at 760 mmHg
• PKA: 4.60±0.10(Predicted)
• Flash Point: 349.7 °C
• PSA: 96.78000
• Density: 1.43 g/cm³
• LogP: 4.56260
• Storage Temp.: Desiccate at -20°C
• Solubility.: DMSO: ≥40mg/mL
• XLogP3: 2.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 6
• Exact Mass: 416.12060649
• Heavy Atom Count: 29
• Complexity: 689

Purity/Quality:

99% ^*data from raw suppliers

BAY-u 3405 ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39-45

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: C1CC2=C(CC1NS(=O)(=O)C3=CC=C(C=C3)F)C4=CC=CC=C4N2CCC(=O)O
• Isomeric SMILES: C1CC2=C(C[C@@H]1NS(=O)(=O)C3=CC=C(C=C3)F)C4=CC=CC=C4N2CCC(=O)O
• Recent ClinicalTrials: Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia
• Recent NIPH Clinical Trials: Efficacy of ramatroban in multiple sclerosis patients
• Description: Ramatroban, originally developed for the treatment of cardiovascular pathologies as thromboembolism, was finally introduced in Japan for the treatment of allergic rhinitis. It is a (3R)-enantiomer that can be synthesized in 5 steps from 3-oxo-1,2,3,4- tetrahydrocarbazole by stereoselective reductive amination, using S-phenethylamine as the chiral source, followed by hydrogenolysis, sulfonylation and finally 2-step Ncarboxyethylation. Ramatroban is a potent antagonist of prostaglandin receptors (PGD2, PGH2) and thromboxane receptors (TxA2); accordingly, it blocks the contractions induced by thromboxane or TxA2-mimetics in animal and human airway smooth muscle. It also prevents, when administered i.v., p.o. or by aerosol, bronchoconstriction induced by PGD2 or antigen. In animal models of nasal allergy, ramatroban inhibits antigen-induced neutrophil infiltration into nasal mucosa and also inhibits nasal symptoms. In several species including humans, it is well-absorbed, extensively protein-bound (>95%) and eliminated mainly as a glucuro-conjugate; in man, its terminal half-life is 2 to 3 hours.
• Uses: A thromboxane receptor antagonist for use in the treatment of coronary artery disease.

Technology Process of Ramatroban

There total 19 articles about Ramatroban which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 79.0%

(R)-N-[9-(2-cyanoethyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-4-fluorobenzenesulfonamide (118699-38-0) → ramatroban (116649-85-5)

Guidance literature:

(R)-N-[9-(2-cyanoethyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-4-fluorobenzenesulfonamide; With water; sodium hydroxide; In isopropyl alcohol; at 100 ℃; for 24h;

With hydrogenchloride; In water;

DOI:10.1021/jo300552v

Reference yield:

1,2,3,4-tetrahydrocarbazol-3-one (51145-61-0) → ramatroban (116649-85-5)

Guidance literature:

Multi-step reaction with 4 steps

1: 2.) tetrabutylammonium borohydride, 3.) 2N sulfuric acid / 1.) benzene, reflux, 1 h, 2.) CH₂Cl₂, -50 deg C to room temperature, 3.) methanol, room temperature, 1 h

2: 1.) 2N NaOH, conc. HCl, 2.) ammonium formiate / 2.) 10percent Pd/C / 1.) methanol, ethyl acetate, 2.) dimethylformamide, reflux, 20 min

3: 84 percent / triethylamine / CH₂Cl₂ / 1 h / Ambient temperature

4: 1.) 80percent sodium hydride (in mineral oil), 2.) 10percent potassium hydroxide / 1.) dimethylformamide, 2 h, room temperature, 2.) isopropanol, reflux, 16 h

With hydrogenchloride; potassium hydroxide; sodium hydroxide; sulfuric acid; ammonium formate; sodium hydride; tetrabutylammonium borohydride; triethylamine; palladium on activated charcoal; In dichloromethane;

Reference yield:

(3R)-3-(1S-phenylethylamino)-1,2,3,4-tetrahydrocarbazole hydrogensulfate → ramatroban (116649-85-5)

Guidance literature:

Multi-step reaction with 3 steps

1: 1.) 2N NaOH, conc. HCl, 2.) ammonium formiate / 2.) 10percent Pd/C / 1.) methanol, ethyl acetate, 2.) dimethylformamide, reflux, 20 min

2: 84 percent / triethylamine / CH₂Cl₂ / 1 h / Ambient temperature

3: 1.) 80percent sodium hydride (in mineral oil), 2.) 10percent potassium hydroxide / 1.) dimethylformamide, 2 h, room temperature, 2.) isopropanol, reflux, 16 h

With hydrogenchloride; potassium hydroxide; sodium hydroxide; ammonium formate; sodium hydride; triethylamine; palladium on activated charcoal; In dichloromethane;

upstream raw materials:

acrylonitrile

(R)-4-fluoro-N-(2,3,4,9-tetrahydro-1H-carbazol-3-yl)benzenesulfonamide

1,2,3,4-tetrahydrocarbazol-3-one

(3R)-2,3,4,9-tetrahydro-1H-carbazol-3-amine

Downstream raw materials:

(R)-methyl 3-[3-(4-fluorophenylsulfonamido)-3,4-dihydro-1H-carbazol-9(2H)-yl]propanoate

Refernces

• 1、 Rosentreter,Boshagen,Seuter,Perzoborn,Fiedler. "Synthesis and absolute configuration of the new thromboxane antagonist (3R)-3-(4-Fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid and comparison with its enantiomer". . p. 1519 - 1521. Retrieved 2007/10/02.