1841-19-6 Usage
Description
Fluspirilene is a potent, non-competitive antagonist of agonist-activated L-type calcium channels (IC50 = 0.03 μM). In addition to its use in research as a calcium channel blocker, fluspirilene has potential application as an antipsychotic in schizophrenia.
Chemical Properties
White or almost white powder.
Originator
Imap, Janssen W. ,Germany ,1972
Uses
Different sources of media describe the Uses of 1841-19-6 differently. You can refer to the following data:
1. This drug is primarily used for supportive therapy of patients suffering from chronic mental illnesses after treatment in the hospital. It is suitable for use in ambulatory practice
because of the lack of expressed hypno-sedative effects.
2. Fluspirilene has been used as a neuroleptic drug to study its effects on human ether-a-go-go related gene (HERG).
3. Antipsychotic.
Manufacturing Process
To a solution of 130 parts cyclopropyl-di-(4-fluorophenyl)-carbinol in 240 parts benzene are added dropwise 43 parts thionylchloride. The whole is refluxed until no more gas is evolved. The reaction mixture is then evaporated. The residue is distilled in vacuo, yielding 4-chloro-1,1-di-(4-fluorophenyl)-1butene, boiling point 165° to 167°C at 6 mm pressure; nD20= 1.5698; d2020= 1.2151.A solution of 61 parts 4-chloro-1,1-di-(4-fluorophenyl)-1-butene in 400 parts 2-propanol is hydrogenated at normal pressure and at room temperature in the presence of 5.5 parts palladium-on-charcoal catalyst 10% (exothermic reaction, temperature rises to about 30°C). After the calculated amount of hydrogen is taken up, hydrogenation is stopped. The catalyst is filtered off and the filtrate is evaporated. The oily residue is distilled in vacuo, yielding 1chloro-4,4-di-(4-fluorophenyl)-butane, boiling point 166° to 168°C at 6 mm pressure; nD20= 1.5425; d2020= 1,2039.A mixture of 7.3 parts 1-chloro-4,4-di-(4-fluorophenyl)-butane, 5.1 parts 1phenyl-4-oxo-1,3,8-triaza-spiro[4,5]decane, 4 parts sodium carbonate, a few crystals of potassium iodide in 200 parts 4-methyl-2-pentanone is stirred and refluxed for 60 hours. After cooling the reaction mixture is treated with water. The organic layer is separated, dried, filtered and evaporated. The solid residue is recrystallized from 80 parts 4-methyl-2-pentanone, yielding 1phenyl-4-oxo-8-[4,4-di-(4-fluorophenyl)]butyl-1,3,8-triaza-spiro[4,5]decane, melting point 187.5° to 190°C.
Brand name
Imap (OrthoMcNeil).
Therapeutic Function
Tranquilizer
Biochem/physiol Actions
Fluspirilene has a potential to inhibit the activity of cyclin-dependent kinase 2 (CDK2). It is an effective anti-cancer agent used for treating human hepatocellular carcinoma.
Synthesis
Fluspirilene, 8-[4,4-bis(p-fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro
[4,5]decan-4-one (6.6.9), is synthesized from 1-benzyl-4-anilino-4-cyanopiperidine
(3.1.64) by the way of its acidic hydrolysis into the amide (6.6.6), and the subsequent heterocyclization of 4-aminocarbonyl and 4-aniline functional groups into imidazolone cycle,
thus creating the desired spiroheterocyclic system, 8-benzyl-1-phenyl-1,3,8-triazaspiro[4,5] decan-4-one (6.6.7). Hydrogenation of this product using a palladium on carbon
catalyst removes the N-benzyl protecting group, forming 1-phenyl-1,3,8-triazaspiro
[4,5]decan-4-one (6.6.8). Alkylating this with 1,1-bis-(4-fluorophenyl)butyl bromide
(6.6.3) gives fluspirilene (6.6.9) [64–66].
in vitro
fluspirilene was found to be weakly active as an antagonist of ca2(+)-induced contractions in k(+)-depolarized taenia. in addition, fluspirilene at 10-1000 nm was a potent non-competitive antagonist of the effects of bay k 8644 on ca2(+)-induced contractions and could selectively antagonise the effects of bay k 8644, without affecting the calcium antagonist effects of nitrendipine [1].
in vivo
in a previous animal study, adult male wistar rats were intramuscularly injected with a 8 mg/kg dose of fluspirilene. results showed that the excretion was slow but constant during the first 12 days. the identified metabolites of the urine and faeces showed oxidative n-dealkylation as the major metabolic pathway [2].
IC 50
0.03 μm
references
[1] kenny, b. a.,fraser, s.,kilpatrick, a.t., et al. selective antagonism of calcium channel activators by fluspirilene. br. j. pharmacol. 100(2), 211-216 (1990).[2] heykants jp. the excretion and metabolism of the long-acting neuroleptic drug fluspirilene in the rat. life sci. 1969 oct 1;8(19):1029-39.[3] chouinard g, annable l, steinberg s. a controlled
Check Digit Verification of cas no
The CAS Registry Mumber 1841-19-6 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 1,8,4 and 1 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1841-19:
(6*1)+(5*8)+(4*4)+(3*1)+(2*1)+(1*9)=76
76 % 10 = 6
So 1841-19-6 is a valid CAS Registry Number.
InChI:InChI=1/C29H31F2N3O/c30-24-12-8-22(9-13-24)27(23-10-14-25(31)15-11-23)7-4-18-33-19-16-29(17-20-33)28(35)32-21-34(29)26-5-2-1-3-6-26/h1-3,5-6,8-15,27H,4,7,16-21H2,(H,32,35)
1841-19-6Relevant articles and documents
Rhodium catalyzed hydroformylation of 1,1-bis(p-fluorophenyl)allyl or propargyl alcohol: A key step in the synthesis of Fluspirilen and Penfluridol
Botteghi, Carlo,Marchetti, Mauro,Paganelli, Stefano,Persi-Paoli, Francesco
, p. 1631 - 1637 (2001)
Fluspirilen (1) and Penfluridol (2), two neuroleptic agents, belong to a wide class of pharmaceuticals that contain in their molecules a 4,4-bis(p-fluorophenyl)butyl group bound to a nitrogen atom of a pyrrolidine, piperidine or piperazine moiety. A key intermediate for the synthesis of compounds 1 and 2,4,4-bis(p-fluorophenyl)butylbromide (15), has been prepared starting from commercially available 4,4′-difluorobenzophenone (7) following a preparative route involving the rhodium catalyzed hydroformylation in toluene or in the biphasic system toluene/water or cyclohexane/water of 1,1-bis(p-fluorophenyl)-2-propenol (8) and/or 1,1-bis(p-fluorophenyl)-2-propynol (12). Fluspirilen and Penfluridol were obtained in 70-80% yield by reaction of bromide 15 with 1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one (16) and 4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol (17), respectively. The overall yields of the two pharmaceuticals 1 and 2, based on starting ketone 7, were about 35-40%.
METHODS FOR TREATING CHRONIC FATIGUE SYNDROME AND MYALGIC ENCEPHALOMYELITIS
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, (2021/03/13)
In one aspect the invention relates to a method of treatment selected from the group consisting of: (a) treating a symptom such as pain in a subject identified or diagnosed as having Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); (b) treating a symptom such as pain in a subject having dysfunctional TRPM3 ion channel activity; (c) restoring NK cell function in a subject having dysfunctional TRPM3 ion channel activity; and (d) restoring calcium homeostasis in a subject having dysfunctional TRPM3 ion channel activity. The method comprises the step of administering to the subject a therapeutically effective amount of at least one therapeutic compound selected from the group consisting of: (i) an opioid receptor antagonist; (ii) an opioid antagonist; and (iii) a therapeutic compound that restores TRPM3 ion channel activity. In some embodiments the therapeutic compound is naltrexone hydrochloride.
DIPHENYLBUTYPIPERIDINE AUTOPHAGY INDUCERS
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Page/Page column 7; 84-85, (2011/12/02)
Autophagy inducing compounds, methods of their preparation and use, and kits containg said compounds are disclosed herein.
