62869-69-6

Basic information

• Product Name: R(-)-QUINUCLIDINYL BENZILATE
• Synonyms: R(-)-QUINUCLIDINYL BENZILATE R(-)-QNB MU SCA;R-(-)-QNB, R-(-)-Quinuclidinyl-α-hydroxydiphenylacetate;(1S,3R,4S)-quinuclidin-3-yl 2-hydroxy-2,2-diphenylacetate(WXG03091)
• CAS NO: 62869-69-6
• Molecular Formula: C₂₁H₂₃NO₃
• Molecular Weight: 337.42
• Mol File: 62869-69-6.mol

Chemical Properties

• Appearance: /
• Storage Temp.: 2-8°C
• CAS DataBase Reference: R(-)-QUINUCLIDINYL BENZILATE(CAS DataBase Reference)
• NIST Chemistry Reference: R(-)-QUINUCLIDINYL BENZILATE(62869-69-6)
• EPA Substance Registry System: R(-)-QUINUCLIDINYL BENZILATE(62869-69-6)

Safety Data

• Hazard Codes: T
• Statements: 23/24/25
• Safety Statements: 22-36/37/39-45
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: DD4638000
• Hazardous Substances Data: 62869-69-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
R(-)-QUINUCLIDINYL BENZILATE is used as a muscarinic M3 antagonist for the inhaled treatment of chronic obstructive pulmonary disease (COPD). As a muscarinic antagonist, it helps to reduce the symptoms associated with COPD by blocking the action of acetylcholine on the muscarinic receptors, leading to improved lung function and reduced inflammation.
The use of R(-)-QUINUCLIDINYL BENZILATE in the treatment of COPD highlights its potential as a targeted therapeutic agent, offering a more specific and effective treatment option for patients suffering from this debilitating respiratory condition. Its chiral nature also allows for the development of enantiomer-specific drugs, which can provide improved safety and efficacy profiles compared to racemic mixtures.

Potential Exposure

Suspected reprotoxic hazard, drug; incapacitating agent. QNB is a glycolate anticholinergic compound that affects the CNS and peripheral nervous sys- tem (PNS) and is related to the drugs atropine, scopol- amine, and hyoscyamine. QNB is nonirritating; symptoms are delayed for several hours. QNB can be used to contami- nate water, food, and agricultural products. A highly potent drug and CNS depressant, QNB is a delayed-action inca- pacitating agent, usually dispersed as an aerosol, but it can also be used to penetrate skin when mixed with a solvent (such as DMSO), and to contaminate food and water. QNB appears to be widely used in pharmacologic research. The key to protection from QNB is prevention from entering the body with good quality aerosol filter and impermeable gloves and clothing. QMB is stable in most solvents, with a half-life of 3 to 4 weeks in moist air; it can be dispersed even with heat-producing munitions.

Incompatibilities

May form explosive mixture with air. Decomposes at about 170℃ in air under prolonged heat- ing. After 1 or 2 hours at 200℃, it is completely decom- posed. Rate of decomposition is both temperature- and purity dependent. No effect on steel or stainless steel after 3 months @ 71℃. Aluminum and anodized aluminum are mildly attacked after 3 months @ 71℃. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanga- nates, perchlorates, chlorine, bromine, fluorine, etc.); con- tact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides. Contact with metals may evolve flammable hydrogen gas

Waste Disposal

Dispose of the material per IAW waste disposal methods provided below. Conduct general area monitoring with an approved monitor to con- firm that the atmospheric concentrations do not exceed the airborne exposure limit. If 10 wt.% sodium hydroxide is not available then the following decontaminants may be used instead and are listed in order of preference: Decontaminating Solution No. 2 , sodium carbonate and Supertropical Bleach Slurry (STB). Keep this chemical out of a confined space, such as a sewer, because of the possibility of an explosion, unless the sewer is designed to prevent the build-up of explosive concentrations. It may be necessary to contain and dispose of this chemical as a hazardous waste. If material or con- taminated runoff enters waterways, notify downstream users of potentially contaminated waters. Contact your local or federal environmental protection agency for specific recommendations. If employees are required to clean-up spills, they must be properly trained and equipped. OSHA 1910.120(q) may be applicable.

Upstream product

• 25333-42-0 (R)-quinuclidin-3-ol 
• 52182-15-7 ethyl benzilate 
• 141831-51-8 (3R)-1-azabicyclo[2.2.2]oct-3-yl oxo(phenyl)acetate 
• 591-51-5 phenyllithium 
• 76-89-1 methyl benzilate 

Downstream Products

• 87395-66-2 fluoro-diphenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl) ester 
• 1195981-96-4 (R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(5-phenylisoxazol-3-ylmethyl)-1-azoniabicyclo[2.2.2]octane chloride 
• 320345-35-5 (3R)-3-{[hydroxy(diphenyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide 

Relevant articles and documents

Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters as potent and long-acting muscarinic antagonists with potential for minimal systemic exposure after inhaled administration: Identification of (3R)-3-{[hydroxy(di-2-thienyl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2. 2.2]octane bromide (aclidinium bromide)

The objective of this work was to discover a novel, long-acting muscarinicM3 antagonist for the inhaled treatment of chronic obstructive pulmonary disease (COPD), with a potentially improved risk-benefit profile compared with current antimuscarinic agents. A series of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters were synthesized and evaluated. On the basis of its overall profile, (3R)-3-{[hydroxy(di-2-thienyl) acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (aclidiniumbromide) emerged as a candidate for once-daily maintenance treatment of COPD. This compound is a potent muscarinic antagonist, with long duration of action in vivo, and was found to have a rapid hydrolysis in human plasma, minimizing the potential to induce class-related systemic side effects. Aclidinium bromide is currently in phase III development for maintenance treatment of patients with COPD.

QUINUCLIDINE DERIVATIVES AND THEIR USE AS MUSCARINIC RECEPTOR ANTAGONISTS

The invention provides compounds of formula (I) wherein R1, R2, R3, Het1, n, Y and X are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them, a process f

Affinity and Selectivity of the Optical Isomers of 3-Quinuclidinyl BenzAlate and Related Muscarinic Antagonists

All the optical isomers of the muscarinic antagonists 3-(1-azabicyclooctyl) α-hydroxy-α,α-diphenylacetate (3-quinuclidinyl benzilate, QNB, 1), 3-(1-azabicyclooctyl)xanthene-9-carboxylate (3-quinuclidinyl xanthene-9-carboxylate, QNX, 2), and 3-(1-azabicyclooctyl) α-hydroxy-α-phenylpropionate (3-quinuclidinyl atrolactate, QNA, 3) were prepared and studied in binding and functional assays.In all instances the esters of (R)-1-azabicyclooctan-3-ol (3-quinuclidinol) had greater affinity for the M1 and M2 subpopulations of muscarinic acetylcholine receptors (M-AChRs) than did their S counterparts.The enantiomers of QNB (1), QNX (2), and QNA (3) in which the alcoholic portion of the muscarinic anatagonists had the S absolute stereochemistry were more selective for the M1-AChRs.This selectivity was modulated by the nature and, in the case of QNA, the chirality of the acid portion.The most potent isomer in the series was (R)-QNB.In the QNA series the diastereoisomer with the absolute R configuration of the alcohol (a) and the R configuration of the acid (b) was the most potent in both binding and functional assays whereas (Sa,Rb)-QNA was the most selective for the M1 subtype of M-AChRs.In fact, the latter diastereomer was as potent and selective as pirenzepine for M1-AChRs.