139404-48-1

Basic information

• Product Name: Tiotropium bromide hydrate
• Synonyms: (1a,2b,4b,5a,7b)-7-[(hydroxydi-2-thienylacety l)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane bromide hydrate;(1a,2b,4b,5a,7b)-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane bromide;(1R,2R,4S,5S,7S)-7-[2-HYDROXY-2,2-DI(2-THIENYL)ACETOXY]-9,9-DIMETHYL-3-OXA-9-AZONIATRICYCLO[3.3.1.02,4] NONANE BROMIDE MONOHYDRATE;tiotropium bromide hydrate;TIOTROPIUM BROMIDE MONOHYDRATE;TIOTROPIUM BROMDIE;Tiotropium;(1α,2β,4β,5α,7β)-7-[(Hydroxydi-2-thienylacety l)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane bromide hydrate
• CAS NO: 139404-48-1
• Molecular Formula: Br*C₁₉H₂₂NO₄S₂
• Molecular Weight: 490.43
• EINECS: 690-508-4
• Product Categories: API;Inhibitors
• Mol File: 139404-48-1.mol
• Article Data: 30

Chemical Properties

• Appearance: /
• Solubility: Sparingly soluble in water, soluble in methanol, practically insoluble in methylene chloride.
• CAS DataBase Reference: Tiotropium bromide hydrate(CAS DataBase Reference)
• NIST Chemistry Reference: Tiotropium bromide hydrate(139404-48-1)
• EPA Substance Registry System: Tiotropium bromide hydrate(139404-48-1)

Safety Data

• Hazardous Substances Data: 139404-48-1(Hazardous Substances Data)

Usage

Chemical Properties

White or yellowish-white powder or crystals.

Uses

Tiotropium Bromide hydrate is a hydrate of tiotropium bromide (Spiriva; Tiova; BA 679BR; tiopropium) that is an anticholinergic and bronchodilator and a muscarinic receptor antagonist. Although tiotropium Bromide (Spiriva; Tiova; BA 679BR; tiopropium) doe

Clinical Use

Maintenance treatment of chronic obstructive pulmonary disease

Drug interactions

Potentially hazardous interactions with other drugs Avoid administration with other anti-cholinergic drugs. Anti-arrhythmics: increased risk of antimuscarinic side effects with disopyramide.

Metabolism

Tiotropium is excreted largely unchanged in the urine, although it may undergo some metabolism by non-enzymatic cleavage and by the cytochrome P450 isoenzymes CYP2D6 and CYP3A4.

Upstream product

• 411207-31-3 tiotropium bromide monohydrate 
• 26447-85-8 hydroxy-di-thiophen-2-yl-acetic acid methyl ester 
• 114-49-8 hyoscine hydrobromide 
• 136310-66-2 (1R,3S,5S)-2'-hydroxy-2',2'-di(thiophen-2''-yl)acetic acid 8-methyl-8-azabicyclo[3.2.1]oct-6-en-3-yl ester 
• 22143-95-9 tropenol 
• 498-45-3 scopine 
• 1336913-22-4 7-(2,2-dithiophen-2-ylacetoxy)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0^2,4]nonane bromide 
• 4408-82-6 2,2-di(thiophen-2-yl)acetic acid 
• 136310-64-0 N-demethyltiotropium 
• 74-83-9 methyl bromide 
• 155-41-9 methylscopolamine bromide 
• 1336913-21-3 C₁₈H₁₉NO₃S₂ 

Relevant articles and documents

Preparation method of tiotropium bromide

The invention provides a preparation method of tiotropium bromide, which comprises the following steps: (1) reacting a compound of a formula I with a compound of a formula II with an alkaline compound to obtain a compound of a formula III, wherein R is methyl, ethyl, isopropyl or tert-butyl, (2) reacting a halogenating agent of the compound of the formula III with a catalyst to obtain a compound of a formula IV, reacting the compound of the formula IV with an alkali to obtain a compound V, wherein X is Cl, Br or I, and (3) reacting the compound of the formula V with methyl bromide to obtain the tiotropium bromide. According to the method, the defect that vanadium pentoxide and hydrogen peroxide-urea are used as epoxidation agents when tropine is used as a raw material to prepare tiotropium bromide in the prior art is overcome, the reaction safety is improved, and meanwhile, the yield of cyclized products is increased.

A PROCESS FOR PREPARING TIOTROPIUM BROMIDE AND INTERMEDIATES THEREOF

Provided herein is a process for synthesis of tiotropium bromide and a process for synthesis of scopine starting from a dimethyl tartarate compound. The synthetic sequence comprises a double Mannich reaction (Robinson-Schopf reaction).

Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists

The marketed long-acting M3 antagonists for treatment of chronic obstructive pulmonary disease have inappropriate plasma stability (either overstable or excessively unstable), which causes substantial systemic exposure or poor patient compliance. To discover novel M3 antagonists with proper plasma stability, we synthesized and biologically evaluated a series of chiral quaternary ammonium salts of pyrrolidinol esters, which were designed by structural recombination of the marketed M3 antagonists. As a result, two novel potent M3 antagonists, (R/S)-3-[2-hydroxy-2,2-di(thiophen-2-yl)acetoxy]-1,1-dimethylpyrrolidinium bromides (1 a: Ki=0.16 nm, IC50=0.38 nm, t1/2=9.34 min; 1 b: Ki=0.32 nm, IC50=1.01 nm, t1/2=19.2 min) with proper plasma stability were identified, which (particularly 1 a) hold great promise as clinical drug candidates to overcome the drawbacks caused by the inappropriate stability of the currently marketed M3 antagonists. In addition, structure–activity relationship studies revealed that the R configuration of the pyrrolidinyl C3 atom was clearly better than the S configuration.