13850-76-5

Usage

Uses

Used in Pharmaceutical Industry:
1-Benzoyl-3-piperidinecarboxylic acid is used as a therapeutic agent for the treatment of neuronal ceroid lipofuscinoses, a group of inherited disorders that affect the nervous system. Its inhibitory effect on the enzyme palmitoyl protein thioesterase 1 (PPT1) makes it a promising candidate for the development of new drugs to address these disorders.
1-Benzoyl-3-piperidinecarboxylic acid is also used as a potential drug candidate for the treatment of neurodegenerative diseases. Its ability to inhibit PPT1 may contribute to the development of new therapeutic approaches for managing these conditions, offering hope for patients suffering from such diseases.

InChI:InChI=1S/C13H15NO3/c15-12(10-5-2-1-3-6-10)14-8-4-7-11(9-14)13(16)17/h1-3,5-6,11H,4,7-9H2,(H,16,17)

Upstream product

• 2067-33-6 5-bromopentanoic acid 
• 98-88-4 benzoyl chloride 
• 498-95-3 nipecotic acid 
• 116140-20-6 ethyl 1-benzoyl-3-piperidinecarboxylate 

Downstream Products

• 113558-93-3 1-benzoyl-3-piperidinecarbonyl chloride 
• 1339097-59-4 (±)-N-((1-benzylpiperidin-3-yl)methyl)-2-methoxyethan-1-amine 
• 1585985-11-0 (±)-N-((1-benzylpiperidin-3-yl)methyl)-3-methoxypropan-1-amine 
• 1585985-05-2 (±)-tert-butyl((1-benzylpiperidin-3-yl)methyl)(2-methoxyethyl)carbamate 
• 1585985-06-3 (±)-tert-butyl ((1-benzylpiperidin-3-yl)methyl)(3-methoxypropyl)carbamate 
• 1585985-09-6 (±)-1-benzoyl-N-(2-methoxyethyl)piperidine-3-carboxamide 
• 1585985-10-9 C₁₇H₂₄N₂O₃ 
• 120569-20-2 (3-chloropiperidin-1-yl)(phenyl)methanone 
• 310454-60-5 n-butyl 1-benzoyl-3-piperidinecarboxylate 
• 107264-25-5 phenyl(3-phenylpiperidin-1-yl)methanone 

Relevant academic research and scientific papers

Synthesis and Initial Characterization of a Reversible, Selective 18F-Labeled Radiotracer for Human Butyrylcholinesterase

Purpose: A neuropathological hallmark of Alzheimer’s disease (AD) is the presence of amyloid-β (Aβ) plaques in the brain, which are observed in a significant number of cognitively normal, older adults as well. In AD, butyrylcholinesterase (BChE) becomes associated with Aβ aggregates, making it a promising target for imaging probes to support diagnosis of AD. In this study, we present the synthesis, radiochemistry, in vitro and preliminary ex and in vivo investigations of a selective, reversible BChE inhibitor as PET-tracer for evaluation as an AD diagnostic. Procedures: Radiolabeling of the inhibitor was achieved by fluorination of a respective tosylated precursor using K[18F]. IC50 values of the fluorinated compound were obtained in a colorimetric assay using recombinant, human (h) BChE. Dissociation constants were determined by measuring hBChE activity in the presence of different concentrations of inhibitor. Results: Radiofluorination of the tosylate precursor gave the desired radiotracer in an average radiochemical yield of 20 ± 3?%. Identity and > 95.5?% radiochemical purity were confirmed by HPLC and TLC autoradiography. The inhibitory potency determined in Ellman’s assay gave an IC50 value of 118.3 ± 19.6?nM. Dissociation constants measured in kinetic experiments revealed lower affinity of the inhibitor for binding to the acylated enzyme (K2 = 68.0?nM) in comparison to the free enzyme (K1 = 32.9?nM). Conclusions: The reversibly acting, selective radiotracer is synthetically easily accessible and retains promising activity and binding potential on hBChE. Radiosynthesis with 18F labeling of tosylates was feasible in a reasonable time frame and good radiochemical yield.

Catalytic Asymmetric Synthesis of Unprotected β2-Amino Acids

We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β2-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β2-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β2-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.

The Magic of Crystal Structure-Based Inhibitor Optimization: Development of a Butyrylcholinesterase Inhibitor with Picomolar Affinity and in Vivo Activity

The enzymatic activity of butyrylcholinesterase (BChE) in the brain increases with the progression of Alzheimer's disease, thus classifying BChE as a promising drug target in advanced Alzheimer's disease. We used structure-based drug discovery approaches to develop potent, selective, and reversible human BChE inhibitors. The most potent, compound 3, had a picomolar inhibition constant versus BChE due to strong cation-π interactions, as revealed by the solved crystal structure of its complex with human BChE. Additionally, compound 3 inhibits BChE ex vivo and is noncytotoxic. In vitro pharmacokinetic experiments show that compound 3 is highly protein bound, highly permeable, and metabolically stable. Finally, compound 3 crosses the blood-brain barrier, and it improves memory, cognitive functions, and learning abilities of mice in a scopolamine model of dementia. Compound 3 is thus a promising advanced lead compound for the development of drugs for alleviating symptoms of cholinergic hypofunction in patients with advanced Alzheimer's disease.

N-Propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2-sulfonamide moieties: Potential multifunctional anti-Alzheimer's agents

In the brains of patients with Alzheimer's disease, the enzymatic activities of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer's disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, we have designed, synthesized and biochemically evaluated a series of N-propargylpiperidines. All of these compounds inhibited hBChE with good selectivity over the related enzyme, acetylcholinesterase, and crossed the blood-brain barrier in a parallel artificial membrane permeation assay. The crystal structure of one of the inhibitors (compound 3) in complex with hBChE revealed its binding mode. Three compounds (4, 5, 6) showed concomitant inhibition of MAO-B. Additionally, the most potent hBChE inhibitor 7 and dual BChE and MAO-B inhibitor 6 were non-cytotoxic and protected neuronal SH-SY5Y cells from toxic amyloid β-peptide species.

DISUBSTITUTED PIPERIDINE DERIVATIVES AS BUTYRYLCHOLINESTERASE INHIBITORS FOR USE IN THE TREATMENT OF ALZHEIMER

This invention relates to new inhibitors of butyrylcholinesterase with general formulas I and II, where substituents are described in patent description. Compounds can be in the form of pure enantiomers or as racemic mixtures, or in the form of pharmaceutically acceptable salts. The present invention relates to the use of these inhibitors for the treatment of Alzheimer's disease and other forms of dementia.

Straightforward synthesis of orthogonally protected piperidin-3- ylmethanamine and piperidin-4-ylmethanamine derivatives

The 1,3- and 1,4-disubstituted piperidines are important building blocks in medicinal chemistry and drug discovery. We present the synthesis of orthogonally protected piperidin-3-ylmethanamine and piperidin-4-ylmethanamine derivatives from commercially available nipecotamide, isonipecotamide, nipecotic acid and isonipecotic acid. This is a straightforward two-step procedure that gives high overall yields. Purification of the intermediates using this procedure is not necessary, and the final compounds are purified by simple flash column chromatography.

Immunopotentiator agents

Novel compounds and methods for preparing same, immunopotentiating compositions, and a method for potentiating the immune system of a host animal. The method comprises administering to the animal an effective amount of an immunopotentiating compound of Formula I or Formula II, or a physiologically acceptable salt.