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

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

Uses

Used in Pharmaceutical Industry:
Tiotropium bromide hydrate is used as a bronchodilator for the treatment of chronic obstructive pulmonary disease (COPD) and other respiratory conditions. It works by blocking the action of acetylcholine, a neurotransmitter that causes constriction of the airways, thereby helping to relax and widen the airways, making it easier for patients to breathe.
Used in Respiratory Medicine:
Tiotropium bromide hydrate is used as an anticholinergic agent to reduce the frequency of COPD exacerbations and improve lung function in patients with moderate to severe chronic obstructive pulmonary disease. Its long-lasting action allows for once-daily dosing, which can help improve patient compliance and quality of life.
Used in Drug Delivery Systems:
Tiotropium bromide hydrate is also used in the development of novel drug delivery systems, such as inhalers and nebulizers, to enhance the efficiency and convenience of administering the medication to patients with respiratory conditions. These systems aim to improve the bioavailability and therapeutic outcomes of the drug while minimizing potential side effects.

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

• 136310-64-0 N-demethyltiotropium 
• 74-83-9 methyl bromide 
• 411207-31-3 tiotropium bromide monohydrate 
• 26447-85-8 hydroxy-di-thiophen-2-yl-acetic acid methyl ester 
• 498-45-3 scopine 
• 4408-82-6 2,2-di(thiophen-2-yl)acetic acid 
• 1336913-22-4 7-(2,2-dithiophen-2-ylacetoxy)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0^2,4]nonane bromide 
• 1374772-94-7 C₁₁H₆O₄S₂ 
• 1508-46-9 6exo,7exo-epoxy-3endo-hydroxy-8,8-dimethyl-nortropanium; bromide 
• 1336913-20-2 di-(2-thienyl)-acetic acid anhydride 
• 1336913-21-3 C₁₈H₁₉NO₃S₂ 
• 155-41-9 methylscopolamine bromide 
• 114-49-8 hyoscine hydrobromide 
• 22143-95-9 tropenol 

Relevant articles and documents

AN IMPROVED PROCESS FOR PREPARATION OF SCOPINE HYDROBROMIDE

The present invention relates to an efficient and industrially advantageous process for the preparation of scopine free base or salts. Said compounds are important intermediates in the synthesis of tiotropium and pharmaceutically acceptable salts thereof. The method provided for preparing scopine free base or its salts has the advantages of a simple operation, high yield and low costs.

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.

PROCESS FOR SYNTHESIS OF TIOTROPIUM BROMIDE MONOHYDRATE

Provided herein is a process for synthesis of tiotropium bromide wherein the coupling of scopine with 2, 2-dithienyl glycolate is achieved by a two step process under mild conditions.

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.

CRYSTALLINE FORM OF TIOTROPIUM BROMIDE

A stable crystalline form of tiotropium bromide, and a process for its preparation with high purity.

IMPROVED PROCESS FOR ACYL TRANSFER REACTIONS

The present invention relates to a novel process for the preparation of esters like Aclidinium, Atropin, Glycopyrroniunn, Tiotropium, Trospium and their respective precursors and derivatives, based on direct acyl transfer reactions.

ELECTROPHILIC ALKYLATING REAGENTS, THEIR PREPARATION AND USE

The present invention provides electrophilic alkylating reagents of formula II, wherein is an aryl group, R2 is an alkyl group, R3 is a substituted phenyl group, wherein the number of substituents (n) is greater than 2 and R4 is an anion, and salts thereof, methods for their preparation and methods for the preparation of alkylated biologically active compounds using such reagents.

METHODS FOR THE SYNTHESIS OF TIOTROPIUM BROMIDE

Present invention relates to methods for preparing (1α, 2β, 4β, 5α, 7β)-7-[(hydroxidi-2-thienllacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane-bromide.

PROCESS FOR THE PREPARATION OF SCOPINE ESTERS

The present invention relates to a process for the preparation of scopine esters, as intermediates in the synthesis of tiotropium bromide. In particular, it relates to a transesterification process between scopine alcohol and an ester of a carboxyl acid in high yields and under conditions suitable for industrial use.