Aclidinium bromide

Base Information

• Chemical Name: Aclidinium bromide
• CAS No.: 320345-99-1
• Molecular Formula: Br*C₂₆H₃₀NO₄S₂
• Molecular Weight: 564.564
• Mol file: 320345-99-1.mol

Synonyms:(3R)-(2-Hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octanebromide;LAS 34273;LAS-W 330;1-Azoniabicyclo[2.2.2]octane,3-[(hydroxydi-2-thienylacetyl)oxy]-1-(3-phenoxypropyl)-, bromide, (3R)- (9CI);1-Azoniabicyclo[2.2.2]octane,3-[(2-hydroxy-2,2-di-2-thienylacetyl)oxy]-1-(3-phenoxypropyl)-, bromide (1:1),(3R)-;

Chemical Property of Aclidinium bromide

Chemical Property:

• Melting Point: 230 °C(Solv: acetonitrile (75-05-8))
• PSA: 112.24000
• LogP: 1.62960
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility.: DMSO (Slightly, Heated), Methanol (Slightly)

Purity/Quality:

98%min ^*data from raw suppliers

AclidiniumBromide ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: In July 2012, aclidinium bromide was approved in the US and the EU for long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disorder (COPD). Aclidinium bromide is in the latter category, acting as a selective antagonist for the muscarinic M3 receptor. M3 receptors are localized in airway smooth muscle, and are the primary subtype responsible for bronchial and tracheal smooth muscle contraction. Muscarinic antagonists are well-established bronchodilators that are effective for treating COPD, but these agents have unwanted side effects if systemically absorbed. Systemic exposure can be limited by inhaled administration, which is the route of delivery for aclidinium bromide. In addition, aclidinium bromide was designed to undergo rapid hydrolysis in human plasma, providing inactive acid and alcohol products, and reducing the potential for systemic side effects. Aclidinium bromide was identified amongst a series of quaternary ammonium (3R)-quinuclidinol esters as having the best combination of high potency (M3 Ki=0.14 nM), long duration of action (29 h for 50% reduction of therapeutic effect in a guinea pig bronchoconstriction model), low oral absorption, and rapid plasma degradation. The synthesis of aclidinium bromide was achieved by reaction of dimethyl oxalate with 2-thienylmagnesium bromide followed by treatment of the resulting methyl ester with (3R)-quinuclidinol in the presence of sodium hydride. Quaternization of the amine was achieved by treatment with 3-phenoxypropyl bromide to give aclidinium bromide.
• Uses: Aclidinium Bromide inhibits human muscarinic AChR M1, M2, M3, M4 and M5 with Ki of 0.1 nM, 0.14 nM, 0.14 nM, 0.21 nM and 0.16 nM, respectively Aclidinium Bromide is a novel long-acting antimuscarinic bronchodilator in phase II clinical trials for the treatment of chronic obstructive pulmonary disease.
• Clinical Use: Aclidinium bromide was approved by the U. S. Food and Drug Administration (FDA) in July 2012 for the treatment of chronic obstructive pulmonary disease (COPD). Marketed by Forest Pharmaceuticals, aclidinium bromide selectively binds to five human muscarinic receptors (M1-M5), and posesses a subnanomolar binding affinity for these particular targets. Administered by inhalation, this medicine has demonstrated favorable onset and duration of action, and its safety profile is an improvement over competitor therapies.

Technology Process of Aclidinium bromide

There total 18 articles about Aclidinium bromide 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: 99.0%

hydroxydithien-2-ylacetic acid 1-aza-bicyclo[2.2.2]oct-3(R)-yl ester (320347-97-5) + 3-phenoxypropyl bromide (588-63-6) → aclidinium bromide (320345-99-1)

Guidance literature:

In chloroform; at 23 ℃; for 72h; Solvent; Inert atmosphere;

Reference yield: 90.0%

→ aclidinium bromide (320345-99-1)

Guidance literature:

In chloroform; acetonitrile; at 20 ℃; for 72h; Inert atmosphere;

Reference yield: 85.0%

(S)-1-azabicyclo[2.2.2]oct-3-ylhydroxy(dithiophen-2-yl)acetate + 3-phenoxypropyl bromide (588-63-6) → 3(S)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (320345-99-1)

Guidance literature:

(S)-1-azabicyclo[2.2.2]oct-3-ylhydroxy(dithiophen-2-yl)acetate; In chloroform; acetonitrile; at 25 - 30 ℃; Large scale;

3-phenoxypropyl bromide; In chloroform; acetonitrile; for 72h; Large scale;

upstream raw materials:

hydroxydithien-2-ylacetic acid 1-aza-bicyclo[2.2.2]oct-3(R)-yl ester

3-phenoxypropyl bromide

hydroxy-di-thiophen-2-yl-acetic acid methyl ester

3-quinuclidinol

Downstream raw materials:

2-hydroxy-2,2-di(thiophen-2-yl)acetic acid

Refernces

• 1、 -. "Novel method for synthesis and purification of aclidinium bromide". Page/Page column 6-9. . Retrieved 2018/12/05.
• 2、 -. "High-purity high-yield aclidinium bromide preparation method suitable for industrial production". Paragraph 0015; 0016; 0017; 0021; 0022; 0026; 0027. . Retrieved 2017/07/21.