315680-06-9

Upstream product

• 28808-26-6 (R)-3-hydroxy-1-methylpiperidine 
• 76-93-7 Benzilic acid 
• 76-89-1 methyl benzilate 
• 315191-13-0 (R)-1-benzylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate 
• 50-00-0 formaldehyd 
• 315680-05-8 Hydroxy-diphenyl-acetic acid (R)-piperidin-3-yl ester 

Downstream Products

• 92842-81-4 (3R)-3-[(hydroxy)(diphenyl)acetoxy]-1,1-dimethylpiperidinium bromide 

Relevant academic research and scientific papers

Optically Active Form of Mepenzolate, and Ameliorating Agent for Chronic Obstructive Pulmonary Disease Which Contains Same as Active Ingredient

An optically active form of mepenzolate bromide is provided. An agent for ameliorating chronic obstructive pulmonary disease that contains the optically active form as an active ingredient and is based on a bronchodilator effect and an anti-inflammatory e

NOVEL COMPOUNDS AS ANTI-TUBERCULAR AGENTS

The present invention relates to novel compounds of formula (1): The present invention also discloses compounds of formula (1) along with other pharmaceutical acceptable excipients and use of the compounds as anti-tubercular agents.

Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and airflow limitations. We recently proposed that the muscarinic antagonist mepenzolate bromide (mepenzolate) would be therapeutically effective against COPD due to its muscarinic receptor-dependent bronchodilatory activity as well as anti-inflammatory properties. Mepenzolate has an asymmetric carbon atom, thus providing us with the opportunity to synthesize both of its enantiomers ((R)- and (S)-mepenzolate) and to examine their biochemical and pharmacological activities. (R)- or (S)-mepenzolate was synthesized by condensation of benzilic acid with (R)- or (S)-alcohol, respectively, followed by quaternization of the tertiary amine. As predicted by computational simulation, a filter-binding assay in vitro revealed that (R)-mepenzolate showed a higher affinity for the muscarinic M3 receptor than (S)-mepenzolate. In vivo, the bronchodilatory activity of (R)-mepenzolate was superior to that of (S)-mepenzolate, whereas anti-inflammatory activity was indistinguishable between the two enantiomers. We confirmed that each mepenzolate maintained its original stereochemistry in the lung when administered intratracheally. These results suggest that (R)-mepenzolate may have superior properties to (S)-mepenzolate as a drug to treat COPD patients given that the former has more potent bronchodilatory activity than the latter.

ORGANIC COMPOUNDS

Compounds of formula (I) in salt or zwitterionic form wherein, wherein R1, R2, R3, R4, R5, J, L and M have the meanings as indicated in the specification, are useful for treating conditions that are mediated by the muscarinic M3 receptor. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.

Synthesis, 18F-labeling, and biological evaluation of piperidyl and pyrrolidyl benzilates as in vivo ligands for muscarinic acetylcholine receptors

A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro Ki values ranged from 0.05 nM to >100 nM. (R)-N-(2-Fluoroethyl)-3-piperidyl benzilate (3-FEPB, 22, Ki = 12.1 nM) and N-(2-fluoroethyl)-4-piperidyl benzilate (4-FEPB, 8, Ki = 1.83 nM) were selected for radiolabeling with fluorine-18. Using alkylation with 2-[18F]fluoroethyl triflate, 3-[18F]FEPB (42) and 4-[18F]-FEPB (43) were produced in 7-9% radiochemical yield and >97% radiochemical purity. For in vivo studies, retention was moderate in mouse brain for 42; however, blocking with scopolamine showed that uptake was not muscarinic cholinergic receptor-mediated. Conversely, 43 exhibited high, receptor-mediated retention in mouse brain, with significant clearance after 1 h. These results suggest that 43 could have applications as an in vivo probe for measuring endogenous acetylcholine levels.