57982-78-2 Usage
Description
BUDIPINE, also known as Parkinsan, is a centrally-active anti-Parkinsonian agent that was launched in Germany. It is synthesized through a three-step process involving a Mannich-aldol sequence to create the 4-phenylpiperidine scaffold, followed by a Friedel-Crafts reaction to introduce the second phenyl ring. BUDIPINE is effective in treating Parkinsonian tremors and is more potent than biperiden. It exhibits use-dependent, open channel, uncompetitive NMDA receptor antagonistic activity, possibly through binding to the PCP site and interacting with sigma binding sites in the frontal cortex. Additionally, BUDIPINE acts as an antagonist at presynaptic muscarinic autoreceptors. Its mechanism of action includes a weak inhibitory effect on dopamine reuptake, inhibition of evoked GABA release with low affinity for GABA-A receptors and benzodiazepine receptors, and a weak inhibitory effect on MAO-B.
Uses
Used in Pharmaceutical Industry:
BUDIPINE is used as an anti-Parkinsonian agent for the treatment of Parkinsonian tremors. Its application is based on its effectiveness in addressing tremors and its potent action compared to other similar drugs like biperiden.
Used in Neurological Treatment:
BUDIPINE is used as a treatment for Parkinson's disease due to its NMDA receptor antagonistic activity, which helps in managing the symptoms of the condition.
Used in Research and Development:
BUDIPINE is used as a research compound for studying the mechanisms of Parkinsonian tremors and the potential development of new treatments for Parkinson's disease and other related neurological disorders.
Manufacturing Process
24.4 g of 1-(t-butyl)-4-hydroxy-4-phenylpiperidine are suspended in 150 ml of
anhydrous benzene. 61.5 g of finely pulverized anhydrous aluminum chloride
are added in portions thereto within 25 min while stirring. The reaction
temperature increases on starting addition of aluminum chloride to about
45°C. After about 20 min the temperature is increased to and maintained at
about 50° to 55°C for about 1 hour. The resulting reaction solution is cooled
to about 20°C and is poured into a mixture of ice and concentrated
hydrochloric acid. After warming the mixture to room temperature, the
hydrochloric acid layer together with the dark oil formed on decomposition is
separated from the benzene layer and is washed with benzene. Water is
added to said hydrochloric acid -oil phase, while stirring, in portions and in an
amount sufficient to produce an almost clear solution. Said acid solution is
rendered alkaline by the addition of 40% sodium hydroxide solution whereby the mixture is well cooled. The alkalized mixture is repeatedly extracted with
ether. The combined ether extracts are dried over anhydrous potassium
carbonate and are concentrated by evaporation of the ether. 24 g of the crude
base are obtained as residue in the form of yellowish oil. A water clear oil
boiling at 129-131°C/0.005 mm Hg is recovered by distillation of said crude
oil in a high vacuum. The oil solidifies to crystals on standing for a short
period of time. After recrystallization from aqueous dimethylformamide, the
resulting 1-methyl-4,4-diphenylpiperidine has a melting point of 72-74°C.
Its hydrochloride is produced by dissolving the base in acetic acid ethyl ester
and adding an ethereal hydrochloric acid solution thereto. After
recrystallization from acetic acid ethyl ester, the melting point of the
hydrochloride is 152-154°C.
Therapeutic Function
Antiparkinsonian, Antidepressant
Check Digit Verification of cas no
The CAS Registry Mumber 57982-78-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,7,9,8 and 2 respectively; the second part has 2 digits, 7 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 57982-78:
(7*5)+(6*7)+(5*9)+(4*8)+(3*2)+(2*7)+(1*8)=182
182 % 10 = 2
So 57982-78-2 is a valid CAS Registry Number.
InChI:InChI=1/C21H27N/c1-20(2,3)22-16-14-21(15-17-22,18-10-6-4-7-11-18)19-12-8-5-9-13-19/h4-13H,14-17H2,1-3H3
57982-78-2Relevant articles and documents
Synthesis, physico-chemical properties and pharmacological screening results of budipine and related 1-alkyl-4,4-diphenylpiperidines
Schaefer,Hackmack,Eistetter,Krueger,Menge,Klosa
, p. 233 - 240 (2007/10/02)
1-Alkyl-4,4-diphenylpiperidines are accessible in a simple manner and with attractive yields by regioselective reaction of certain piperidine derivatives, particularly 3-aroyl-4-aryl-4-hydroxypiperidines, which can be varied widely at the nitrogen atom, with benzene under Friedel-Crafts conditions. The physico-chemical parameters, which are important for the transport and the distribution of a drug in a living system, are discussed for the 1-tert-butyl derivative (13) (budipine) (pK(a), partition coefficient P, saturation concentration c(s), surface activity, protein binding). Rapid absorption of this drug in man is indicated by the size of the permeability coefficient P(M) of the passive transport through artificial phospholipid collodium membranes as well as the invasion curves calculated from P(M). According to pharmacological screening tests, most of the compounds of this class show marked antagonistic activity against experimentally generated pathological states in mice (tremorine and reserpine antagonism) which suggest their potential use in the therapy of Parkinson's disease. 13 has been selected for detailed investigations. Structure-activity analyses did not readily demonstrate the presence of a relationship between the type of alkyl substituent at the piperidine nitrogen atom and the pharmacological screening results obtained.
