58-39-9 Usage
Description
Perphenazine (58-39-9) is a clinically useful typical antipsychotic drug. The therapeutic mode of action is not well understood but it binds to a wide variety of receptors including serotonin, histamine, dopamine, and α-adrenergic.1 Perphenazine is an inhibitor of acid sphingomyelinase(ASM)2 and positively affected xenografted tumor growth via perturbation of intracellular cholesterol transport through ASM3. It has also been shown to be an inhibitor of glutamate dehydrogenase.4
Chemical Properties
Off-White to Pale Yellow Solid
Originator
Trilafon, Schering ,US ,1957
Uses
D2 dopamine receptor antagonist; α-adrenergic receptor antagonist and σ-receptor agonist; phenothiazine antipsychotic. Inhibits glutamate dehydrogenase in vitro. Antipsychotic.
Definition
ChEBI: A phenothiazine derivative in which the phenothiazine tricycle carries a chloro substituent at the 2-position and a 3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl group at N-10.
Manufacturing Process
A mixture of 155 parts of 2-chloro-10-(γ-chloropropyl)phenothiazine, 76 partsof sodium iodide, 216 parts of piperazine and 2,000 parts of butanone is refluxed for 8 hours, concentrated and extracted with dilute hydrochloric acid. The extract is rendered alkaline by addition of dilute potassium carbonate and benzene or chloroform extracted. This extract is washed with water, dried over anhydrous potassium carbonate, filtered and evaporated. Vacuum distillation at 0.1 mm pressure yields 2-chloro-10-[γ-(N-piperazino)propyl]phenothiazine at about 214°-218°C.A stirred mixture of 5 parts of 2-chloro-10-[γ-(Npiperazino)propyl]phenothiazine, 1.92 parts of 2-bromoethanol, 2.11 parts of potassium carbonate and 35 parts of toluene is refluxed for 5 hours. The mixture is treated with water and benzene and the organic layer is separated, washed with water, dried over anhydrous potassium carbonate, filtered and evaporated. The residue is distilled at about 240°-244°C and 0.15 mm pressure to yield 2-chloro-10-[γ-(N'-β-hydroxyethyl-N-piperazino)propyl]phenothiazine according to US Patent 2,838,507.The 2-chloro-10-(γ-chloropropyl)phenothiazine starting material is produced from 2-chlorophenothiazine and 1-bromo-3-chloropropane.
Brand name
Trilafon (Schering).
Therapeutic Function
Tranquilizer
General Description
Perphenazine, 4-[3-(2-chlorophenothiazine-10-yl)propyl]piperazineethanol; 2-chloro-10-[3-[4-(2-hydroxyethyl)piperazinyl]propyl]phenothiazine(Trilafon), is an effective antipsychotic and antiemetic.
Biochem/physiol Actions
D2 dopamine receptor antagonist; α-adrenergic receptor antagonist and σ-receptor agonist; phenothiazine antipsychotic. Inhibits glutamate dehydrogenase in vitro.
Safety Profile
Poison by ingestion,
intravenous, subcutaneous, intraperitoneal,
and intramuscular routes. Human systemic
effects by intramuscular route: muscle
spasms. Experimental teratogenic and
reproductive effects. Human mutation data
reported. When heated to decomposition it
emits very toxic fumes of SOx, NOx, and
cl-.
References
1) Kroeze et al. (2003), H1-Histamine Receptor Affinity Predicts Short-Term Weight Gain for Typical and Atypical Antipsychotic Drugs; Neuropharmacology, 28 519
2) Kornhuber et al. (2011), Identification of Novel Functional Inhibitors of Acid Sphingomyelinase; PLoS One, 6 e23852
3) Kuzu et al. (2017), Modulating cancer cell survival by targeting intracellular cholesterol transport; Br. J. Cancer,?117 513
4) Couee and Tipton (1990), Inhibition of ox brain glutamate by perphenazine; Biochem. Pharmacol. 39 1167
Check Digit Verification of cas no
The CAS Registry Mumber 58-39-9 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 8 respectively; the second part has 2 digits, 3 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 58-39:
(4*5)+(3*8)+(2*3)+(1*9)=59
59 % 10 = 9
So 58-39-9 is a valid CAS Registry Number.
InChI:InChI=1/C21H26ClN3OS/c22-17-6-7-21-19(16-17)25(18-4-1-2-5-20(18)27-21)9-3-8-23-10-12-24(13-11-23)14-15-26/h1-2,4-7,16,26H,3,8-15H2
58-39-9Relevant articles and documents
NOVEL SALTS OF CONJUGATED PSYCHOTROPIC DRUGS AND PROCESSES OF PREPARING SAME
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Page/Page column 54, (2008/06/13)
Novel chemical conjugates of a psychotropic drug residue and an amino-containing organic acid residue selected to reduce side effects induced by the psychotropic drug when administered per se, to enhance the therapeutic activity of the psychotropic drug and/or to exert anti-proliferative activity, in which the amino group is in the form of an acid addition salt thereof and which are characterized by high stability are disclosed. Further disclosed are processes for preparing the chemical conjugates and addition salts thereof, pharmaceutical compositions containing the chemical conjugates and methods utilizing the chemical conjugates for treating various medical conditions.
