113-59-7 Usage
Description
Chlorprothixene is a thioxanthene antipsychotic medication that belongs to the class of neuroleptic agents. It is chemically related to phenothiazines and is primarily used in the treatment of various psychiatric conditions. Chlorprothixene works by blocking dopamine receptors in the brain, which helps to alleviate symptoms of psychosis and other mental health disorders.
Uses
Used in Psychiatry:
Chlorprothixene is used as an antipsychotic and sedative agent for the treatment of various psychoses, including schizophrenia, senile psychosis, and borderline personality disorder. It is also used in the management of agitation, mania, and anxiety associated with fear and stress. Additionally, it can be used in small doses as a sedative agent in neurosis.
Used in Neurosis:
Chlorprothixene is used as a muscle relaxant for skeletal muscles, helping to alleviate muscle spasms and pain associated with various etiologies.
Used in Schizophrenia and Psychosis:
Chlorprothixene is used as an alternative drug of choice for anxiety and herpetic neuralgia, as well as in adjunctive therapy for conditions such as schizophrenia and psychosis.
Used in Antidepressant Therapy:
Chlorprothixene is used in the treatment of depression, particularly in combination with other medications to enhance chemo-sensitivity and efficacy in resistant cases.
Used in Postoperative Care:
Chlorprothixene is used as an antiemetic agent to manage postoperative nausea and vomiting, as well as for sedation and pain management.
Used in Childhood Behavior Problems:
Chlorprothixene is used to address behavioral complications in children, particularly in cases where other treatments have been ineffective.
Used in Dementia:
Chlorprothixene is used to manage symptoms of dementia, including agitation and aggression.
Used in Labyrinthine Disorders and Prolactinoma:
Chlorprothixene is used to treat labyrinthine disorders and prolactinoma, a type of pituitary tumor.
Used in Acute Bipolar Mania:
Chlorprothixene is used in the treatment of acute bipolar mania, helping to stabilize mood and reduce symptoms of mania.
Used in Urinary Tract Infections:
Chlorprothixene is used to provide relief from discomfort associated with mild urinary tract infections.
Used in Antimicrobial Applications:
Some thioxanthenes, including chlorprothixene, have shown signs of possible human therapeutic potential against tumors in mice and in vitro assays, as well as cytotoxic and antimicrobial activities.
Brand Name:
Chlorprothixene is available under the brand name Taractan (Roche).
Originator
aractan, Roche, France ,1960
Manufacturing Process
Chlorprothixene may be prepared as described in US Patent 2,951,082.
Magnesium turnings, 4.86 g (0.2 g-atom) was placed in a 500 ml reaction
flask fitted with a mercury sealed stirrer, reflux condenser and a dropping
funnel. Tetrahydrofuran, 50 ml and calcium hydride, 500 mg, were added.
Ethyl bromide, 2.18 g and a crystal of iodine then were added. A vigorous
reaction set in that evolved sufficient heat to induce refluxing. After 5
minutes, a solution of 3-dimethylaminopropyl chloride (dried over calcium
hydride) in 50 ml of tetrahydrofuran was added to the refluxing solution at
such a rate that gentle refluxing was maintained. The addition required 25
minutes.The reaction mixture was stirred at reflux for an additional 30 minutes when
nearly all of the magnesium had dissolved and determination of magnesium in
an aliquot of the solution showed that an 82% yield of Grignard reagent had
been obtained. The reaction mixture was cooled in an ice bath and stirred
while 24.67 g (0.1 mol) of 2-chlorothiaxanthone was added over a period of
10 minutes. The reaction was stirred at room temperature for 30 minutes
then allowed to stand overnight in the refrigerator. The tetrahydrofuran was
evaporated at 50°C under reduced pressure. Benzene, 150 ml, was added to
the residue.The mixture was hydrolyzed in the cold by the dropwise addition of 50 ml of
water. The benzene layer was separated by decantation and the gelatinous
precipitate washed with two 100 ml portions of benzene.The precipitate was then mixed with diatomaceous earth, collected on a filter,
and washed with water and extracted with two 100 ml portions of boilingbenzene. The aqueous filtrate was extracted with 50 ml of benzene, the
combined benzene extracts washed with water and evaporated to dryness
under reduced pressure. The crystalline residue, MP 140° to 147°C, weighed
30.8 g. Recrystallization from a mixture of benzene and hexane gave 27.6 g
(83%) of 2-chloro-10-(3-dimethylaminopropyl)-10-hydroxythiaxanthene, MP
152° to 154°C. Analytically pure material from another experiment melted at
153° to 154°C.2-Chloro-10-(3-dimethylaminopropyl)-10-hydroxythiaxanthene, 3.34 g (0.01
mol) obtained as described was dissolved in 15 ml of dry, alcohol-free
chloroform. Acetyl chloride, 2.36 g (0.03 mol) was added and the clear yellow
solution was refluxed for one hour in a system protected by a drying tube.
The solvent then was evaporated on the steam bath under reduced pressure
and the residue dissolved in absolute alcohol. The hydrochloride of 2-chloro-
10-(3-dimethylaminopropylidene)-thiaxanthene was precipitated by the
cautious addition of absolute ether. After drying at 70°C the yield of white
crystalline 2-chloro10-(3-dimethylaminopropylidene)-thiaxanthene
hydrochloride, MP 189 to 190°C (to a cloudy melt), was 3.20 g (90%). This
material is a mixture of geometric isomers.Trans-2-chloro-9-(ω-dimethylamino-propylidene)-thioxanthene [MP 98°C, MP
of the hydrochloride 225°C (corr.)], is a valuable medicinal agent, being used
as a tranquilizer and antiemetic agent, whereas the corresponding cis isomer
(MP 44°C, MP of the hydrochloride 209°C) is not useful for these indications,
as described in US Patent 3,115,502, which describes procedures for
conversion of the cis to the trans form.
Therapeutic Function
Tranquilizer
Synthesis
Chlorprothixene, 2-chloro-9[(1-dimethylamino)-3-propyliden]thioxanthene (6.2.7), has been proposed to synthesize starting from 2-chlorothixantone (6.2.3). The
initial 2-chlorothixantone (6.2.3) is prepared from 2-mercaptobenzoic acid, the reaction of which with 1-bromo-4-chlorobenzene forms 2-(4-chlorophenylthio)benzoic acid (6.2.1),
which upon reaction with phosphorous pentachloride transforms into acid chloride (6.2.2),
and further undergoes intramolecular cyclization with the use of aluminum chloride to give 2-
chlorthioxantone (6.2.3) [32]. An alternative way of making 2-chlorthioxantone (6.2.3) is by
making 2-(4-chlorophenylthio)benzoic acid (6.2.1) by reacting 2-iodobenzoic acid with 4-
chlorothiophenol [33]. The resulting 2-chlorthioxantone (6.2.3) is reacted as a carbonyl component with either 3-dimethylaminopropylmagnesiumbromide [33], or with
allylmagnesiumbromide [34–36], giving the corresponding tertiary alcohol (6.2.4) or (6.2.5).
Dehydration of the first is accomplished by acylation of the tertiary hydroxyl group using
acetyl chloride and the subsequent pyrolysis of the formed acetate, which leads to the desired
chlorprothixene (6.2.7).
Dehydration of the tertiary alcohol (6.2.5) is accomplished by chlorination of the tertiary alcohol group by thionyl chloride, forming the diene 2-chloro-9-(3-propen-1-
iliden)thioxanthene (6.2.6), the addition to which of dimethylamine at high temperature
forms the desired chlorprothixene (6.2.7).
Environmental Fate
Long-range transport: handling of thioxanthenes should
only be performed by personnel trained and familiar
with handling potent active pharmaceutical ingredients.
In case of handling, avoid inhalation and contact with
skin, eyes, and clothing, as these materials may be an
irritant. These substances are considered nonhazardous
for transport.
Toxicity evaluation
Thioxanthenes work primarily by blocking postsynaptic
dopamine-mediated neurotransmission by binding to dopamine
(DA-1 and DA-2) receptors. In addition to significant
antidopaminergic action, the thioxanthenes also possess weak
anticholinergic and serotonergic blockade, moderate a-adrenergic
blockade, quinidine-like effects, and depress the release of
most hypothalamic and hypophyseal hormones. Thioxanthenes
may also inhibit presynaptic dopamine autoreceptors.
The concentration of prolactin is increased due to
blockade of prolactin inhibitory factor, which inhibits the
release of prolactin from the pituitary gland. Chlorprothixene
also inhibits the medullary chemoreceptor trigger zone to
produce an antiemetic effect; and is thought to cause an indirect
reduction of stimuli to the brain stem reticular system to
produce a sedative effect.
Check Digit Verification of cas no
The CAS Registry Mumber 113-59-7 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,1 and 3 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 113-59:
(5*1)+(4*1)+(3*3)+(2*5)+(1*9)=37
37 % 10 = 7
So 113-59-7 is a valid CAS Registry Number.
InChI:InChI=1/C18H18ClNS.ClH/c1-20(2)11-5-7-14-15-6-3-4-8-17(15)21-18-10-9-13(19)12-16(14)18;/h3-4,6-10,12H,5,11H2,1-2H3;1H/b14-7+;
113-59-7Relevant articles and documents
Photophysics and photochemistry of z-chlorprothixene in acetonitrile
Pinero, Luis E.,Garcia, Carmelo,Lhiaubet-Vallet, Virginie,Oyola, Rolando,Miranda, Miguel A.
, p. 895 - 900 (2009)
Chlorprothixene (CPTX, Taractan) is a low potency antipsychotic mainly used for the treatment of psychotic disorders (e.g. schizophrenia) and acute mania occurring as part of bipolar disorders. As in the case of other numerous drugs used in the
