63-75-2

Basic information

• Product Name: arecoline
• Synonyms: NICOTINICACID,1,2,5,6-TETRAHYDRO-1-METHYL-,METHYLESTER;1,2,5,6-Tetrahydro-1-methyl-3-pyridinecarboxylic Acid Methyl Ester;1-Methyl-1,2,5,6-tetrahydro-pyridine-3-carboxylic Acid Methyl Ester;Arecaidine Methyl Ester;Arecolin;Methylarecaidine;NSC 56321;1,2,5,6-Tetrahydro-1-methyl-3-pyridinecarboxylic acid methyl
• CAS NO: 63-75-2
• Molecular Formula: C₈H₁₃NO₂
• Molecular Weight: 155.196
• EINECS: 200-565-5
• Product Categories: Heterocyclic Compounds;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals
• Mol File: 63-75-2.mol

Chemical Properties

• Melting Point: <25℃
• Boiling Point: 209℃
• Flash Point: 81.1°C
• Appearance: Yellow Oil
• Density: 1.0504 g/cm3 (20 ºC)
• Vapor Pressure: 0.208mmHg at 25°C
• Refractive Index: 1.4860 (589.3 nm 20℃)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• PKA: 6.84(at 25℃)
• CAS DataBase Reference: arecoline(CAS DataBase Reference)
• NIST Chemistry Reference: arecoline(63-75-2)
• EPA Substance Registry System: arecoline(63-75-2)

Safety Data

• Hazardous Substances Data: 63-75-2(Hazardous Substances Data)

Usage

Chemical Description

Arecoline is a natural alkaloid found in the areca nut and is used as a substrate in the reaction.

Uses

Used in Pharmaceutical Industry:
Arecoline is used as an anthelmintic agent, particularly effective against cestodes. It is also used as a cathartic, aiding in the treatment of constipation.
Used in Medical Research:
Arecoline has shown regulatory properties in controlling plasminogen activator inhibitor-1 expression in human buccal mucosa fibroblasts, which can be beneficial in various medical applications.
Used in Traditional Chinese Medicine:
Areca nut, the source of arecoline, has been used as an important medicine in traditional Chinese medicine, particularly for its anthelminthic properties with arecoline as the main alkaloid.

History

Arecoline, an alkaloid extracted from Areca catechu L., is first reported by Jahns in 1888. Mujumdar found that there were at least six kinds of alkaloids in areca, including arecoline, arecaidine, guavacoline, and guavacine. The content of arecoline in the fresh fruit of areca was 0.3–0.63% as determined with HPLC .It has been found first that arecoline has the effect of antiparasite and is promoting the motility of the gastrointestinal smooth muscle. It activates the M and N cholinergic receptors, excites the nervous system, promotes the body excitability, and improves the ability of learning and memory .

Indications

This product has no source standard. Tablets: anthelmintics, less used now. Eye drops: cholinergic drugs for glaucoma treatment.

Pharmacology

Paralysis was the main mechanism of the antiparasite effect of arecoline. The effect of arecoline on cholinergic receptors is similar to that of pilocarpine. It can agonize M-cholinergic receptors (M1, M2, M3, M4) and increase the secretion of glands, especially the salivary. It can also agonize N-cholinergic receptors and activate the muscles of skeletal, ganglia, carotid body, etc. The central nervous system is also influenced by the cholinergic effect of arecoline. Intravenous injection of small dosage of arecoline can cause wake-up reaction of the cortex in cats, which is inhibited or blocked by atropine. Arecoline can cause salivation, vomiting, diuretic, lethargy, and convulsion when overdosed.In addition, arecoline can enhance intestinal peristalsis, contract bronchus, lower heart rate, dilate blood vessels, and decrease blood pressure. While in rabbit, it induces coronary artery contraction.Eye drops can reduce the pupil.Pharmacokinetic parameters for arecoline after oral administration of arecoline (3? mg/kg): Tmax, 120.07? min; Cmax, 60.61? ng/mL; t1/2, 69.32? min; AUC0? – t, 15116.86? min/ng/mL; AUC0-∞, 15771.37? min/ng/mL; plasma clearance, 0.19? L/ min/kg .

Clinical Use

Arecoline is of historical interest, because its structure, like those of many other early medicinal agents, was determined and confirmed by a 19th-century German pharmacist, E. Jahns. Xanomeline may be viewed as a nonclassical bio-isostere of the ester moiety of arecoline. It is a muscarinic M1/M4 agonist that is showing promise in clinical trials for the treatment of Alzheimer's disease. Although it is not tolerated at orally effective doses, transdermal delivery systems are showing promise.

Safety Profile

Poison by subcutaneous and intraperitoneal routes. Moderately toxic by ingestion. Questionable carcinogen with experimental neoplastigenic data. It mimics the action of acetylcholine, a neurotransmitter, and is a parasympathetic nervous system stimulant. Its action on the central nervous system can cause tremors. Human mutation data reported. It is easily nitrosated to several nitrosamines. See also ESTERS and NITROSAMINES. It is the major alkaloid found in betel quid. Combustible, can react with oxidzing materials. When heated to decomposition it emits hghly toxic fumes of NOx.

Upstream product

• 499-04-7 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid 
• 5657-66-9 3-cyano-1-methyl-1,2,5,6-tetrahydropyridine 
• 4685-10-3 3-(methoxycarbonyl)-1-methylpyridinium iodide 
• 144-62-7 oxalic acid 
• 86343-57-9 N-Methyl-3-carbomethoxy-4-hydroxypiperidine 
• 117912-07-9 (3S,4S)-4-(4-Chloro-phenylsulfanyl)-1-methyl-piperidine-3-carboxylic acid methyl ester 
• 67-56-1 methanol 
• 300-08-3 arecoline hydrobromide 
• 94008-32-9 4-(p-chlorothiophenoxy)-1-methylpiperidine-3-carbonitrile 
• 37673-66-8 4-hydroxy-1-methyl-piperidine-3-carboxylic acid ethyl ester 
• 25012-72-0 ethyl 1-methyl-4-oxo-piperidin-3-carboxylate 
• 6315-60-2 3,3'-methylimino-di-propionic acid diethyl ester 
• 59-67-6 nicotinic acid 
• 74-88-4 methyl iodide 

Downstream Products

• 102206-67-7 1-Methyl-3-diphenylmethyl-piperidein-(3) 
• 499-04-7 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylic acid 
• 5809-87-0 1-methyl-1,2,5,6-tetrahydropyridine-3-carboxamide 
• 500562-32-3 4-amino-1-methyl-piperidine-3-carboxylic acid amide 
• 82820-63-1 Toluene-4-sulfonate5-methoxycarbonyl-1-methyl-1-methylamino-1,2,3,6-tetrahydro-pyridinium; 
• 98942-82-6 methyl 1-methyl-5-(phenylhydrazono)-1,2,5,6-tetrahydropyridine-3-carboxylate 
• 98942-81-5 (3RS)-methyl 1-methyl-3-(phenyldiazo)-1,2,3,6-tetrahydropyridine-3-carboxylate 
• 98942-92-8 (5RS,1'RS)-methyl 5-(1'hydroxy-1'-methylbenzyl)-1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate 
• 98942-93-9 (5RS,1'SR)-methyl 5-(1'hydroxy-1'-methylbenzyl)-1-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate 
• 1142-19-4 4,4'-dichlorodiphenyl disulfide 
• 117912-07-9 (3R,4S)-4-(4-Chloro-phenylsulfanyl)-1-methyl-piperidine-3-carboxylic acid methyl ester 
• 117912-07-9 (3S,4S)-4-(4-Chloro-phenylsulfanyl)-1-methyl-piperidine-3-carboxylic acid methyl ester 
• 98942-79-1 (3RS)-methyl 1-methyl-3-phenyl-1,2,3,6-tetrahydropyridine-3-carboxylate 
• 1690-72-8 dihydroarecoline 

Relevant articles and documents

Synthetic method of arecoline

The invention discloses a synthetic method of arecoline. The synthetic method comprises the following steps: taking methyl 3-bromopropionate as an initial raw material, sequentially carrying out sodium methoxide claisen ester condensation, methylamine cyclization, sodium borohydride reduction and dehydration under alkaline conditions to obtain arecoline. According to the method, methyl 3-bromopropionate and a methylamine alcohol solution are used as the raw materials so that the problem that methyl iodide or highly toxic dimethyl sulfate with high cost is used in an N-methylation step, and the safety is controlled from the source is avoided.

Preparation method of arecoline

The invention provides a preparation method of arecoline. On the presence of organic base, reaction raw materials such as nicotinic acid and the like have esterification and alkylation reactions with a compound capable of providing alkyl in the organic solvent, and arecoline can be prepared through a reduction reaction and aftertreatment. Two procedures including esterification and N-methylation are combined, and the process route of preparation of arecoline is shortened. According to the method, the operation conditions are simple, and the intermediate treatment is more convenient; expensive alkyl halide (such as methyl iodide) cannot be used as a reaction raw material, cheaper sulfolipid or phosphate ester compounds are selected, a good implementation effect is also obtained, and the product has a cost advantage.

N-Heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid a novel scaffold for the design of uncompetitive α-glucosidase inhibitors

Abstract The enzyme α-glucosidase has attracted interest owing to its involvement in the digestive process of carbohydrate, its role in intracellular glycoprotein trafficking, tumorigenesis and viral infection. In this study, several members of a new family of N-heteroarylmethyl substituted azasugars were synthesized and evaluated as α-glucosidase inhibitors. We systematically investigated the effect of different N-substituents as well as the role of hydroxyl and carboxylate moieties on the piperidine ring. The compounds N-heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid emerged as potent α-glucosidase inhibitors. Unlike Acarbose and other clinically relevant α-glucosidase inhibitors, these compounds act through a reversible uncompetitive mechanism of inhibition which make them attractive candidates for drug development.

CYCLIC AMINE AZAHETEROCYCLIC CARBOXAMIDES

The invention provides novel cyclic amine azaheterocyclic carboxamide according to Formula (I), Formula (II) and Formula (III) their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.

SULFONYLPYRAZOLE AND SULFONYLPYRAZOLINE CARBOXAMIDINE DERIVATIVES AS 5-HT6 ANTAGONISTS

This invention concerns sulfonylpyrazoline carboxamidine derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1), wherein the symbols have the meanings given in the description.

Beta-sulfonamide hydroxamic acid inhibitors of tace/matrix metalloproteinase

This invention provides compounds of Formula I, having the structure: that are useful in treating diseases or disorders mediated by TNF-α, such as arthritis (rheumatoid arthritis (RA), juvenile RA, psoriatic arthritis, osteoarthritis etc), tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection, ankylosing spondylitis, psoriasis, sepsis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, asthma, idiopathic pulmonary fibrosis, vasculitis, systemic lupus erythematosus, irritable bowel syndrome, acute coronary syndrome, hepatitis C, cachexia, COPD, stroke or type 2 diabetes, and for alleviation of symptoms thereof. The invention further provides methods for use of the compounds.

New carbamoylpiperidines as human platelet aggregation inhibitors

A series of 3-carbamoylpiperidines (nipecotamides) are designed, synthesized and tested for their inhibitory action against adenosine diphosphate (ADP)-induced aggregation of human platelets. A structure- activity analysis of the bis(nipecotamido)aralkane type showed that a substituent on the piperidine ring should preferably be an amide and that the electronegativity of the carbonyl oxygen and the orientation of the amide group affected activities. Based on the knowledge of factors influencing platelet activation and aggregation, a nitric ester moiety which could release nitric oxide (NO) in situ, is incorporated into the nipecotamide structure. These compounds exhibit increased activity compared to those having no -ONO2 function. They also show stereoselectivity, with the meso isomer being approximately twice as potent as the synthetic diastereomeric mixture. Replacement of the -ONO2 function with hydroxyl, ester or alkyl groups considerably diminishes aggregation-inhibitory potential. Nipecotamides are shown here to inhibit the basal and collagen-induced rise in platelet inositol trisphosphate (IP3) levels, as well as phosphoinositide turnover. A comprehensive mechanism of action is proposed taking earlier results into consideration. (C) 2000 Elsevier Science Ltd.

Preparation and Stereochemistry of Methyl 3-(and 4)-p-Chlorothiophenoxy-1-methylpiperidine-4-(and 3)-carboxylates, and Cyclization to Benzothiopyranopyridinones

The title piperidines were prepared by (a) methanolysis of the corresponding nitriles and (b) addition of p-chlorothiophenol to the appropriate tetrahydropyridines.Three esters were obtained with stereochemistry assigned by nmr analysis: 2 , 5 , 6 .Compounds 2 and 6 cyclized in 70percent sulfuric acid.The product structures were established by X-ray crystallography and, suprisingly, both had trans-fused rings.Compound 5, however, did not cyclize but gave 4-(methylthio)chlorobenzene as the sole isolated product.