504-24-5 Usage
Description
4-Aminopyridine, also known as 4-AP, fampridine, or dalfampridine, is a compound that has been approved by the FDA as the first drug to improve walking in patients with multiple sclerosis (MS). It functions as a voltage-gated potassium channel blocker, which allows it to penetrate the central nervous system (CNS) and enhance the conduction and duration of action potential across nerve fibers. This results in improved functionality, particularly in the walking speed of MS patients.
Uses
Used in Pharmaceutical Industry:
4-Aminopyridine is used as a therapeutic agent for the treatment of multiple sclerosis. It is used as a potassium channel blocker to improve walking speed in MS patients with gait impairment. However, it is contraindicated in patients with a history of seizures or moderate to severe renal impairment due to its potential adverse effects.
Used in Veterinary Industry:
4-Aminopyridine, under the name Avitrol, is used as a bird repellent and toxicant. It is classified as a severe poison and irritant, and can be used as a broadcast bait to cause uncoordinated flight, distress calls, and escape responses in nearby birds, making it useful for managing bird populations in certain areas.
Used in Research:
Dalfampridine, a form of 4-aminopyridine, is utilized in the characterization of subtypes of potassium channels. This aids researchers in understanding the mechanisms of these channels and their role in various physiological processes. Additionally, it has been used to manage some symptoms of multiple sclerosis and is a precursor to the drug Pinacidil, further expanding its applications in medical research and treatment.
Originator
Rush University Medical Center (United States)
Reactivity Profile
4-Aminopyridine neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.
Health Hazard
4-Aminopyridine, a pyridine compound, is an extremely effective bird poison. In agriculture, 4-AP is used as an extremely effective bird poison sold under the brand name Avitrol. It is highly toxic to all mammals including humans if dosages are exceeded, and as an experimental drug, the recommended dose data is unavailable.
Fire Hazard
Material may produce irritating or poisonous gases in fire. Runoff from fire control water may give off irritating or poisonous gases.
Safety Profile
Poison by ingestion, subcutaneous, intravenous, and intraperitoneal routes. Human systemic effects by ingestion: hallucinations and vomiting. When heated to decomposition it emits toxic fumes of NOx,.
Potential Exposure
Used as a chemical intermediate in pharmaceuticals; as an agricultural chemical for field crops; and as a bird repellent and poison
in vitro
4-ap acts by selectively blocking fast, voltage-gated k+ channels in excitable tissues. in axons, k+ channel blockade increases the safety factor1 across demyelinated internodes and 4-ap can, therefore, restore conduction in focally demyelinated axons. 4-ap also increases calcium (ca2+) influx at presynaptic terminals thereby enabling an enhancement of neuroneuronal or neuromuscular transmission in normally myelinated neurons [1].
in vivo
investigations of the effects of 4-ap on neurologic deficits in animal in vivo models of demyelinating disease or sci have yielded inconsistent results. some trials have shown indications of potential neurological benefit, such as enhanced motor evoked potentials or reflex activity, while others have yielded no evident gains in function [1].
IC 50
170 and 230 μm at kv1.1 and kv1.2, respectively
Shipping
UN2671 Aminopyridines, Hazard Class: 6.1; Labels: 6.1-Poisonous materials
Purification Methods
Crystallise the aminopyridine from *benzene/EtOH, then recrystallise it twice from water, then crush and dry it for 4hours at 105o [Bates & Hetzer J Res Nat Bur Stand 64A 427 1960]. It has also been crystallised from EtOH, *benzene, *benzene/pet ether, toluene and sublimes in a vacuum. [Beilstein 22/9 V 106.]
Toxicity evaluation
4-Aminopyridine is highly toxic to animals, with an approximate oral LD50 of 3.7 mg/kg body weight in the dog. 4-Aminopyridine blocks potassium channels, resulting in increased cholinergic nervous system activity. The ability of 4-aminopyridine to block potassium channels has led to some speculation that it may be an effective therapy for multiple sclerosis. Clinical signs in poisoned animals often develop within several hours of ingestion and commonly include tachycardia, salivation, tremors, ataxia, and seizures. Death from respiratory failure may develop within 4 hours of exposure. Chemical analysis of frozen stomach contents, liver, and urine is available at some diagnostic laboratories, and residues can be detected in poisoned birds. Although no specifi c antidotal therapy exists, anticonvulsants and activated charcoal administration are recommended.
Incompatibilities
Sodium nitrite, strong oxidizers. Avoid contact with acid anhydrides, acid chlorides; and strong acids.
Waste Disposal
Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposalIncineration with nitrogen oxides removal from effluent gas.
references
[1] hayes kc. the use of 4-aminopyridine (fampridine) in demyelinating disorders. cns drug rev. 2004 winter;10(4):295-316.
Check Digit Verification of cas no
The CAS Registry Mumber 504-24-5 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,0 and 4 respectively; the second part has 2 digits, 2 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 504-24:
(5*5)+(4*0)+(3*4)+(2*2)+(1*4)=45
45 % 10 = 5
So 504-24-5 is a valid CAS Registry Number.
InChI:InChI=1/C5H6N2/c6-5-1-3-7-4-2-5/h1-4H,(H2,6,7)/p+1
504-24-5Relevant articles and documents
Crystal Engineering in Supramolecular Polyoxometalate Hybrids through pH Controlled in Situ Ligand Hydrolysis
Roy, Soumyabrata,Mumbaraddi, Dundappa,Jain, Ankit,George, Subi J.,Peter, Sebastian C.
, p. 590 - 601 (2018)
A family of five different three-dimensional polyoxometalate (POM) based supramolecular hybrids were synthesized by a hydrothermal route under different pH using a hydrolyzable naphthalene diimide ligand. The mechanism of crystallographic phase variation of the POM-amino pyridine hybrids under different pH was studied through controlled experiments where the final hydrolyzed products were analyzed through NMR and single crystal X-ray diffraction. Different pH conditions led to variation in the extent of protonation and hydrolyzation of the ligand, yielding different phases. All of these were identified, and the structures of the supramolecular hybrids were characterized extensively. Mechanistic study proved that only the reaction conditions are responsible for the hydrolysis of the ligand and the in situ generated POM species do not have any role in it. Magnetic measurements confirmed the hexavalent oxidation states of the transition metal center (Mo) in the POM. Optical band gap measurements revealed that these hybrids are semiconducting in nature. Two of the compounds were studied for hydrogen peroxide mediated selective oxidation catalysis of small organic molecules and found to exhibit very good activity with high percentage of selectivity for the desired products of industrial importance.
Indirect reduction of CO2and recycling of polymers by manganese-catalyzed transfer hydrogenation of amides, carbamates, urea derivatives, and polyurethanes
Liu, Xin,Werner, Thomas
, p. 10590 - 10597 (2021/08/20)
The reduction of polar bonds, in particular carbonyl groups, is of fundamental importance in organic chemistry and biology. Herein, we report a manganese pincer complex as a versatile catalyst for the transfer hydrogenation of amides, carbamates, urea derivatives, and even polyurethanes leading to the corresponding alcohols, amines, and methanol as products. Since these compound classes can be prepared using CO2as a C1 building block the reported reaction represents an approach to the indirect reduction of CO2. Notably, these are the first examples on the reduction of carbamates and urea derivatives as well as on the C-N bond cleavage in amides by transfer hydrogenation. The general applicability of this methodology is highlighted by the successful reduction of 12 urea derivatives, 26 carbamates and 11 amides. The corresponding amines, alcohols and methanol were obtained in good to excellent yields up to 97%. Furthermore, polyurethanes were successfully converted which represents a viable strategy towards a circular economy. Based on control experiments and the observed intermediates a feasible mechanism is proposed.
Preparation method and post-treatment process of 4-aminopyridine
-
Paragraph 0021-0039, (2020/06/02)
The invention relates to a preparation method and a post-treatment process of 4-aminopyridine. The preparation method comprises the following steps: with isonicotine as an initial raw material, carrying out a Hofmann degradation reaction in a sodium hypochlorite solution and a sodium hydroxide solution, carrying out cooling treatment on a reaction solution, and then successively performing activated carbon decoloration, cooling crystallization, vacuum filtration and drying, and secondary recrystallization and drying to obtain a final 4-aminopyridine product. The whole reaction conditions are mild and easy to control, the operation is simple, the purity of the 4-aminopyridine reaches 99% or above, and the post-treatment process is simple, convenient and easy to operate, has a total yield of90% or above and is a post-treatment technology suitable for industrial production and application.
Copper(ii)-catalyzed c-n coupling of aryl halides and n-nucleophiles promoted by quebrachitol or diethylene glycol
Chen, Guoliang,Chen, Yuanguang,Du, Fangyu,Fu, Yang,Wu, Ying,Zhou, Qifan
supporting information, p. 2161 - 2168 (2019/11/25)
Herein, we report the natural ligand quebrachitol (QCT) as a promoter for a Cu(II) catalyst, which is highly effective for N-Arylation of various amines and related aryl halides. A series of diarylamine derivatives were obtained in high yields by using diethylene glycol (DEG) as both ligand and solvent. The C-N coupling reactions proceed under mild conditions and exhibit good functional group tolerance.