Tiotropium bromide

Base Information

• Chemical Name: Tiotropium bromide
• CAS No.: 136310-93-5
• Molecular Formula: C19H22BrNO4S2
• Molecular Weight: 472.42
• Hs Code.: 29309070
• European Community (EC) Number: 680-665-7
• UNII: XX112XZP0J
• DSSTox Substance ID: DTXSID2044214
• Wikipedia: Tiotropium_bromide
• Wikidata: Q27162952
• NCI Thesaurus Code: C84608
• RXCUI: 1298831,2462023
• Pharos Ligand ID: V9WJR53ZWQSP,V9WVZL1VCUB7
• ChEMBL ID: CHEMBL4638964,CHEMBL4440620,CHEMBL3189058
• Mol file: 136310-93-5.mol

Synonyms:679 BR, BA;7-((hydroxybis(2-thienyl)acetyl)oxy)-9,9-dimethyl-3-oxa-9-azoniatricyclo(3.3.1.0(2,4))nonane bromide;BA 679 BR;BA-679 BR;BA679 BR;BR, BA 679;Bromide, Tiotropium;Spiriva;tiotropium;tiotropium bromide

Chemical Property of Tiotropium bromide

Chemical Property:

• Appearance/Colour: White solid
• Melting Point: 218-2200C
• PSA: 115.54000
• LogP: -0.69150
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 5
• Exact Mass: 471.01736
• Heavy Atom Count: 27
• Complexity: 564

Purity/Quality:

99%, ^*data from raw suppliers

Tiotropium bromide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C[N+]1(C2CC(CC1C3C2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-]
• Isomeric SMILES: C[N+]1([C@@H]2CC(C[C@H]1[C@H]3[C@@H]2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-]
• Recent ClinicalTrials: Tiotropium Handihaler vs. Tiotropium Respimat in COPD
• Recent EU Clinical Trials: A prospective multicenter placebo-controlled trial to study the efficacy and safety of Tiotropium in preventing severe asthma exacerbations in partial and uncontrolled preschool asthma. TIPP-Study
• Description: Tiotropium bromide is a long-acting inhaled muscarinic antagonist, developed for the once-daily treatment of chronic obstructive pulmonary disease. Tiotropium bromide can be prepared in three steps. The Grignard condensation of 2-thienyl magnesium bromide with oxalic acid dimethyl ester, followed by a transesterlfication with scopine provided the ester which was quaternized with methyl bromide. Tiotropium bromide binds to human recombinant muscarinic receptors M1-, M2- and M3-subtypes with high and similar affinity, comparable to those obtained with ipratropium. Tiotropium bromide is characterized by its novel property of kinetic selectivity : while ipratropium rapidly dissociated from each of the receptor subtypes, tiotropium dissociated rapidly from M2 receptors (t1/2=3.6 h) but slowly from MI (t1/2=14.6 h) and M3 (t1/2=34.7 h) receptors. Inhibition of cholinergic bronchospasm by tiotropium bromide was demonstrated in anesthetized guinea pigs, rabbits and dogs. In healthy volunteers, inhalation of tiotropium bromide resulted in an absolute bioavailability of 19.5%, a t,,, value of 5 min. and the terminal half-life value of 5-6 days. There was no evidence of drug accumulation after repeated administration. The extent of biotransfonation was small with a urinary excretion of 74% of unchanged substance after iv. administration. Long term studies in patients with stable COPD have demonstrated that tiotropium bromide gave an effective bronchodilation that was maintained over 24h, significantly improved lung function as measured by FEVI (+ll-12%) and showed progressive reduction in dyspnea. It also reduced exacerbations of COPD patients and improved quality of life. Tiotropium bromide produced greater and more sustained bronchodilation than ipratropium bromide. Tiotropium has been shown to cause superior bronchodilatation and symptomatic improvements when compared to twice daily salmeterol in COPD. Tiotropium bromide was well tolerated and caused few adverse effects. The most common side effect reported was the mechanism-related effect of dry mouth. Tiotropium is an antagonist that binds to M1, M2, and M3 muscarinic acetylcholine receptors (Kds = 0.43, 0.54, and 0.69 nM, respectively, for human receptors). It decreases acetylcholine-induced contraction of isolated guinea pig trachea in a concentration-dependent manner. In vivo, tiotropium (1 g/L inhaled aerosol) confers complete protection against acetylcholine-induced bronchospasms in anesthetized dogs. Formulations containing tiotropium have been used in the treatment of chronic obstructive pulmonary disease (COPD).
• Uses: Muscarinic receptor antagonist. Bronchodilator Specially selective choline drug resistance Anti - Asthmatic
• Clinical Use: Tiotropium is the dithienyl derivative of N-methyl scopolamine, a quaternary analogue of naturally occurring scopolamine in Atropa belladonna. It is indicated primarily for the relief of bronchospasms associated with COPD and can be considered to be a site-specific, local medication to the lung.