136722-67-3

Upstream product

• 5407-98-7 1-cyclobutyl-1-phenyl-methanone 
• 944324-82-7 (+/-)-1-cyclobutyl-1-hydroxy-1-phenylacetonitrile 
• 944324-87-2 (+/-)-[(1-cyano-1-cyclobutyl-1-phenylmethoxy)carbonyl]methyl acetate 
• 944325-08-0 (R)-(+)-1-cyano-1-cyclobutyl-1-phenylmethyl hydroxyacetate 
• 1460-47-5 2-cyclobutyl-2-hydroxy-2-phenylacetic acid 

Downstream Products

• 136722-65-1 (-)-1-cyclobutyl-1-phenyl-1-(trimethylsiloxy)-2-propanone 
• 136722-65-1 (+)-1-cyclobutyl-1-phenyl-1-(trimethylsiloxy)-2-propanone 
• 133151-45-8 (-)-1-cyclobutyl-7-(dimethylamino)-1-hydroxy-1-phenyl-5-heptyn-2-one 
• 133151-45-8 (+)-1-cyclobutyl-7-(dimethylamino)-1-hydroxy-1-phenyl-5-heptyn-2-one 

Relevant academic research and scientific papers

Enzymatic resolution of hindered cyanohydrins, key precursors of muscarinic receptor antagonists

Enantiomerically pure 1-cycloalkyl-1-hydroxy-1-phenylcyanohydrins, key precursors in the synthesis of (S)-oxybutynin and other antimuscarinic agents, have been successfully prepared via lipase-catalyzed kinetic resolutions. Pseudomonas cepacia and Candida antarctica lipase B have shown excellent enantioselectivities in hydrolysis and acylation processes, depending on the substrate structure and the reaction conditions. Furthermore, molecular modeling of phosphonate transition state analogue for the C. antarctica lipase B enzymatic hydrolysis resolution step supports these facts, which were experimentally observed.

1,4-di-substituted piperidine derivatives

This invention provides novel 1,4-di-substituted piperidine derivatives of the general formula ?I! STR1 and the pharmaceutically acceptable salts thereof, wherein: Ar represents a phenyl group or a five- or six-membered heteroaromatic group having one or two hetero atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom in which one or two optional hydrogen atoms on the ring may be replaced by substituent groups selected from the group consisting of a halogen atom and a lower alkyl group; R1 represents a cycloalkyl group of 3 to 6 carbon atoms or a cycloalkenyl group of 3 to 6 carbon atoms; R2 represents a saturated or unsaturated aliphatic hydrocarbon radical of 5 to 15 carbon atoms; and X represents O or NH. These compounds have selective antagonistic activity against the muscarinic M3 receptors and can hence be used safely with a minimum of side effects.

Analogues of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds

Oxybutynin chloride [4-(diethylamino)-2-butynyl α-cyclohexyl-α-hydroxybenzeneacetate hydrochloride, Ditropan] is widely used for the relief of symptoms in neurogenic bladder. This is a result of its combined anticholinergic, antispasmodic, and local anesthetic activities. In a study directed toward development of agents possessing the beneficial properties of oxybutynin, but having a longer duration of action, a series of metabolically more stable keto analogues of the parent ester, i.e. substituted 7-amino-1-hydroxy-5-heptyn-2-ones along with some analogues and derivatives, was prepared and evaluated for in vitro and in vivo antimuscarinic action in guinea pig preparations. Several members of the series were potent antimuscarinics having a longer duration of activity than that of oxybutynin in a guinea pig cystometrogram model. On the basis of its in vitro and in vivo antimuscarinic activity, coupled with a 5-fold greater duration of action than that of oxybutynin, 1-cyclobutyl-7-(dimethylamino)-1-hydroxy-1-phenyl-5-heptyn-2-one (14b) was selected for clinical evaluation.