58258-01-8

Usage

Chemical Properties

Low Melting Light-Brown Solid

InChI:InChI=1/C18H21NO/c1-3-7-15(8-4-1)18(16-9-5-2-6-10-16)20-17-11-13-19-14-12-17/h1-10,17-19H,11-14H2

Upstream product

• 133993-06-3 methyl 4-diphenylmethoxypiperidine-1-carboxylate 
• 110480-68-7 1-acetyl-4-benzhydryloxypiperidine 
• 65214-84-8 ethyl 4-(diphenylmethoxy)-1-piperidinecarboxylate 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 91-01-0 1,1-Diphenylmethanol 
• 147-20-6 diphenylpyraline 
• 776-74-9 Bromodiphenylmethane 
• 100-58-3 phenylmagnesium bromide 
• 100-52-7 benzaldehyde 
• 1614234-70-6 benzyl 4-(benzhydryloxy)piperidine-1-carboxylate 
• 14629-59-5 diphenylmethyl trimethylsilyl ether 
• 1338066-81-1 4-benzhydryloxypiperidine toluenesulfonate 
• 75250-52-1 4-hydroxy-piperidine-1-carboxylic acid methyl ester 
• 4045-22-1 N-acetyl-4-hydroxypiperidine 

Downstream Products

• 125602-76-8 ethyl 4-(4-benzhydryloxypiperidino)butanoate 
• 133016-99-6 ethyl 3-[4-(diphenylmethoxy)piperidin-1-yl]propanoate 
• 661481-71-6 5-(4-Benzhydryloxy-piperidin-1-yl)-pentanoic acid ethyl ester 
• 770685-45-5 6-(4-Benzhydryloxy-piperidin-1-yl)-hexanoic acid methyl ester 
• 133015-42-6 ethyl <(4-diphenylmethoxy)piperidino>acetate 
• 101620-71-7 2-[3-(4-benzhydryloxy-piperidin-1-yl)-propyl]-isoindole-1,3-dione 
• 215530-54-4 4-(diphenylmethoxy)-1-piperidinepropanol 
• 97927-85-0 4-[4-[4-(Hydroxydiphenylmethyl-)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetic acid ethyl ester 
• 189064-48-0 4-[4-[4-(Hydroxydiphenylmethyl-)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylbenzeneacetic acid methyl ester 
• 215530-56-6 6-(4-diphenylmethoxy-piperidin-1-yl)-hexan-1-ol 

Relevant academic research and scientific papers

Electrochemical: N -demethylation of tropane alkaloids

A practical, efficient, and selective electrochemical N-demethylation method of tropane alkaloids to their nortropane derivatives is described. Nortropanes, such as noratropine and norscopolamine, are important intermediates for the semi-synthesis of the medicines ipratropium or oxitropium bromide, respectively. Synthesis was performed in a simple home-made electrochemical batch cell using a porous glassy carbon electrode. The reaction proceeds at room temperature in one step in a mixture of ethanol or methanol and water. The method avoids hazardous oxidizing agents such as H2O2 or m-chloroperbenzoic acid (m-CPBA), toxic solvents such as chloroform, as well as metal-based catalysts. Various key parameters were investigated in electrochemical batch or flow cells, and the optimized conditions were used in batch and flow-cells at gram scale to synthesize noratropine in high yield and purity using a convenient liquid-liquid extraction method without any need for chromatographic purification. Mechanistic studies showed that the electrochemical N-demethylation proceeds by the formation of an iminium intermediate which is converted by water as the nucleophile. The optimized method was further applied to scopolamine, cocaine, benzatropine, homatropine and tropacocaine, showing that this is a generic way of N-demethylating tropane alkaloids to synthesize valuable precursors for pharmaceutical products.

Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment

Monoacylglycerol lipase (MGL) inhibition provides a potential treatment approach to glaucoma through the regulation of ocular 2-arachidonoylglycerol (2-AG) levels and the activation of CB1 receptors. Herein, we report the discovery of new series of carbamates as highly potent and selective MGL inhibitors. The new inhibitors showed potent nanomolar inhibitory activity against recombinant human and purified rat MGL, were selective (>1000-fold) against serine hydrolases FAAH and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Protein-based 1H NMR experiments indicated that inhibitor 2 rapidly formed a covalent adduct with MGL with a residence time of about 6 h. This interconversion process “intrinsic reversibility” was exploited by modifications of the ligand's size (length and bulkiness) to generate analogs with “tunable’ adduct residence time (τ). Inhibitor 2 was evaluated in a normotensive murine model for assessing intraocular pressure (IOP), which could lead to glaucoma, a major cause of blindness. Inhibitor 2 was found to decrease ocular pressure by ～4.5 mmHg in a sustained manner for at least 12 h after a single ocular application, underscoring the potential for topically-administered MGL inhibitors as a novel therapeutic target for the treatment of glaucoma.

A biocatalytic/reductive etherification approach to substituted piperidinyl ethers

A synthetically useful protocol has been developed for the preparation of highly functionalized piperidinyl ethers. Biocatalytic reduction of cyclhexanones 7, 10, and 14 allows for the preparation of both cis- and trans diastereomers with an extremely high degree of stereochemical control. Reductive etherification of the corresponding trimethylsilylethers with 1-(benzyloxycarbonyl)-4-piperidinone 17 in the presence of triethylsilane and catalytic TMSO-Tf provides the desired piperidinyl ethers in good to excellent yields. Finally hygrogenolysis of the nitrogen protecting group leads to piperidinyl ethers in near quantitative yields. Application of the methodology to a range of piperidinyl ethers, including the core scaffolds of diphenylpyraline and ebastine, is also described.

HETEROCYCLIC COMPOUND AND H1 RECEPTOR ANTAGONIST

A heterocyclic compound useful as an antiallergic agent is provided. A compound represented by the following formula (1) or a salt thereof: wherein the ring A is a homocyclic or heterocyclic ring; the ring B is a heterocyclic ring which contains G and nitrogen atom N as constituent atoms thereof, wherein G is CH or N; R1 is a carbonyl group or an alkylene group; R2a and R2b are an alkyl group, a cycloalkyl group, an aryl group, or a heterocyclic group; X is an oxygen atom or a sulfur atom; Z is a hydroxyl group, an alkoxy group, a cycloalkyloxy group, an aryloxy group, an aralkyloxy group, an amino group, or an N-substituted amino group; and n is 0 or 1; with the proviso that when the ring A is a benzene ring or when the ring B is a piperazine ring, R1 is an alkylene group which may have a substituent.

Process for the preparation of 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-(diphenylmethoxy)-1-piperidinyl]-1-butanone and acid addition salts thereof

The present invention describes processes for the preparation of 1-[4-(1,1-dimethylethyl)phenyl]-4-[4-(diphenylmethoxy)-1-piperidinyl]-1-butanone and acid addition salts thereof.

PROCESS FOR THE PREPARATION OF 1-[4-(1,1-DIMETHYLETHYL)PHENYL]-4-[4-(DIPHENYLMETHOXY)-1-PIPERIDINYL]-1-BUTANONE AND ACID ADDITION SALTS THEREOF

The present invention describes processes for the preparation of 1-[4-(11,- dimethylethyl)phenyl] -4- [4-(diphenylmethoxy)- 1 -piperidinyl] - 1 -butanone and acid addition salts thereof.

Synthesis, in vitro assay, and molecular modeling of new piperidine derivatives having dual inhibitory potency against acetylcholinesterase and Aβ1-42 aggregation for Alzheimer's disease therapeutics

With the goal of developing Alzheimer's disease therapeutics, we have designed and synthesized new piperidine derivatives having dual action of acetylcholinesterase (AChE) and beta-amyloid peptide (Aβ) aggregation inhibition. For binding with the catalytic site of AChE, an ester with aromatic group was designed, and for the peripheral site, another aromatic group was considered. And for intercalating amyloid-beta oligomerization, long and linear conformation with a lipophilic group was considered. The synthetic methods employed for the structure with dual action depended on alcohols with an aromatic ring and the substituted benzoic acids, which are esterificated in the last step of the synthetic pathway. We screened these new derivatives through inhibition tests of acetylcholinesterase, butyrylcholinesterase (BChE), and Aβ1-42 peptide aggregation, AChE-induced Aβ1-42 aggregation. Our results displayed that compound 12 showed the best inhibitory potency and selectivity of AChE, and 29 showed the highest selectivity of BChE inhibition. Compounds 15 and 12 had inhibitory activities against Aβ1-42 aggregation and AChE-induced Aβ aggregation. In the docking model, we confirmed that 4-chlorobenzene of 12 plays the parallel π-π stacking against the indole ring of Trp84 in the bottom gorge of AChE. Because the benzyhydryl moiety of 12 covered the peripheral site of AChE in a funnel-like shape, 12 showed good inhibitory potency against AChE and could inhibit AChE-induced Aβ1-42 peptide aggregation.

Treatment of CNS disorders using CNS target modulators

The invention is directed to compositions and methods useful for treating Central Nervous System (CNS) disorders. Furthermore, the invention provides compositions and methods of treating sleep disorders. More specifically, the invention is directed to the compositions and use of derivatized, histamine antagonists for the treatment of sleep disorders.

TREATMENT OF CNS DISORDERS USING CNS TARGET MODULATORS

The invention is directed to compositions used for treating Central Nervous System (CNS) disorders. In addition, the invention provides convenient methods of treatment of a CNS disorder. Furthermore, the invention provides methods of treating sleep disorders using compositions that remain active for a discrete period of time to reduce side effects. More specifically, the invention is directed to the compositions and use of derivatized, e.g., ester or carboxylic acid derivatized, antihistamine antagonists for the treatment of sleep disorders.

Triazolo and derivatives as chemokine inhibitors

Novel triazolo derivatives represented by the following formula and pharmaceutically acceptable salts thereof, as well as chemokine inhibitors containing the same as an effective component. These are useful as therapeutic agents for allergic diseases such