50-53-3 Usage
Description
This phenothiazine with sedative properties is used in
human medicines and has induced contact dermatitis
in nurses or in those working in the pharmaceutical
industry. It is also used in veterinary medicine to avoid
mortality of pigs during transportation. It is a sensitizer
and a photosensitizer.
Chemical Properties
Oily liquid; amine odor.
Uses
Different sources of media describe the Uses of 50-53-3 differently. You can refer to the following data:
1. In psychiatric practice, chlorpromazine is used in various conditions of psychomotor
excitement in patients with schizophrenia, chronic paranoid and also manic-depressive
conditions, neurosis, alcohol psychosis and neurosis accompanied by excitement, fear,
stress, and insomnia. In comparison with other neuroleptics, chlorpromazine is unique in
that it has an expressed sedative effect. It is sometimes used in anesthesiological practice
for potentiating narcosis. It also has moderate anticonvulsant action.
2. antiemetic, antipsychotic
3. Chlorpromazine is approved by FDA for use in humans for the
management of psychotic disorders (i.e., control of mania,
treatment of schizophrenia); control of nausea and vomiting;
relief of apprehension before surgery; acute intermittent
porphyria; adjunctive treatment of tetanus; intractable hiccups;
combativeness or explosive hyperexcitable behavior in children
aged 1–12 years; and short-term treatment of hyperactivity in
children with symptoms of impulsivity, difficulty sustaining
attention, aggressiveness, mood lability, and poor frustration
tolerance. Chlorpromazine is commonly used off-label for
treatment of behavioral symptoms associated with dementia in
the elderly and psychosis and agitation related to Alzheimer’s
dementia; however, it carries a boxed warning regarding increased risk of death in patients with dementia-related
psychosis. Chlorpromazine is also used off-label for managing
agitation in terminal cancer patients, autonomic dysreflexia,
cancer pain, adjunctive treatment of cholera, migraine headaches,
opioid withdrawal, ocular pain, paralytic ileus, and
phantom limb syndrome.
In veterinary medicine, the use of chlorpromazine has been
largely replaced by the phenothiazine acepromazine due to its
more favorable pharmacokinetic profile. Chlorpromazine may
be used as an antiemetic for small animals or for preoperative
sedation. Chlorpromazine may also be used for management
of hypertension in dogs and cats.
Definition
ChEBI: A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety.
Brand name
Thorazine (GlaxoSmithKline).
Hazard
Toxic by ingestion.
Contact allergens
This phenothiazine with sedative properties is used in
human medicine and induced contact dermatitis in nurses
or those working in the pharmaceutical industry. It is also
used in veterinary medicine to avoid mortality of pigs during
transportation. It is a sensitizer and a photosensitizer.
Synthesis
Chlorpromazine, 2-chloro-10-(3-dimethylaminopropyl)phenothiazine, is synthesized in an analogous manner, except by alkylation of 2-chlorophenothiazine with 3-dimethylaminopropylchloride.
Environmental Fate
Acute and chronic toxicity due to chlorpromazine generally
manifests as an extension of normal pharmacological activity.
The precise mechanism of action of chlorpromazine, and other
phenothiazines, is unknown; however, it is thought to primarily
involve antagonism of dopaminergic (D2) neurotransmission
at synaptic sites and blockade of postsynaptic dopamine
receptor sites at the subcortical levels of the reticular formation,
limbic system, and hypothalamus. This activity contributes to
chlorpromazine’s extrapyramidal reactions. Chlorpromazine
also has strong central and peripheral activity directed against
adrenergic receptors and weak activity against serotonergic,
histaminic (H1), and muscarinic receptors. Chlorpromazine
has slight ganglionic blocking action. Chlorpromazine is
known to depress vasomotor reflexes medicated by the hypothalamus
and/or brain stem; inhibit release of growth hormone;
antagonize secretion of prolactin release-inhibiting hormone;
and reduce secretion of corticotropin-regulatory hormone.
Chlorpromazine also has direct effects on cardiac myocytes;
it can induce early after-depolarizations, block depolarizing
sodium channels, and cause significant prolongation of the
QTc interval.
Chlorpromazine may be irritating to eyes, mucous
membranes, and skin. Contact and inhalation should be
avoided.
Metabolic pathway
The in vivo photodegradation of chlorpromazine in rat
skin exposed to UV-A results in the formation of
promazine and 2-hydroxypromazine in irradiated rats,
but not in the skin of rats kept in the dark.
Chlorpromazine sulfoxide is a major metabolite of
chlorpromazine, found in smaller quantity in the skin of
irradiated rats compared with those kept in the dark.
Chlorpromazine sulfoxide is not a photoproduct of
chlorpromazine under the experimental conditions.
Toxicity evaluation
Chlorpromazine exists as both a vapor and particulate at
ambient atmospheric conditions. Chlorpromazine vapor is
degraded by photochemically produced hydroxyl radicals
with an estimated half-life of 1.6 h. Chlorpromazine particulate
is removed by wet or dry deposition. Chlorpromazine is
likely to be immobile in soil (Koc 9900, pKa 9.3) and to
adsorb to sediment if released into water. It is not expected to
volatilize from soil or water. There is high potential for
bioconcentration.
Check Digit Verification of cas no
The CAS Registry Mumber 50-53-3 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 0 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 50-53:
(4*5)+(3*0)+(2*5)+(1*3)=33
33 % 10 = 3
So 50-53-3 is a valid CAS Registry Number.
InChI:InChI=1/C17H19ClN2S.ClH/c1-19(2)10-5-11-20-14-6-3-4-7-16(14)21-17-9-8-13(18)12-15(17)20;/h3-4,6-9,12H,5,10-11H2,1-2H3;1H
50-53-3Relevant articles and documents
Spatially Resolved Spectroelectrochemical Examination of the Oxidation of Dopamine by Chlorpromazine Cation Radical
Deputy, Andrew,Wu, Huan-Ping,McCreery, Richard L.
, p. 3620 - 3624 (1990)
Spatially resolved absorption measurements of electrogenerated chlorpromazine cation radical (CPZ.+) were used to monitor the kinetics of the homogeneous oxidation of dopamine (DA) in the solution near planar and cylindrical electrodes.Complete concentration vs distance profiles for CPZ.+ were obtained for both planar and convergent diffusion and were used to determine the reaction mechanism and rate constants.The oxidation of DA by CPZ.+ to dopamine orthoquinone involves successive one-electron transfers, and the results are inconsistent with disproportionation of the DA semiquinone.The observed kinetics and rate-limiting step were dependent on the position within the diffusion layer.Near the electrode surface the rate law is first order in CPZ.* and DA, and a second-order rate constant of 2.1 x 105 M-1s-1 was obtained.Further away from the electrode the reaction is second order in CPZ.+ due to the involvement of the second step, and several kinetic parameters for the second electron transfer were obtained.A change in diffusion geometry which occurs at a microwire electrode further perturbs local concentration distributions, and the reaction reaches equilibrium under certain conditions.In all cases, the observed rate laws were consistent with a general expression for the stepwise electron transfer.This report represents the first application of spatially resolved spectroelectrochemistry to a kinetic system and provides unprecedented detail about the CPZ.+/DA reaction.
One-Pot Tandem Access to Phenothiazine Derivatives from Acetanilide and 2-Bromothiophenol via Rhodium-Catalyzed C-H Thiolation and Copper-Catalyzed C-N Amination
Rui, Xiyan,Wang, Chao,Si, Dongjuan,Hui, Xuechao,Li, Keting,Wen, Hongmei,Li, Wei,Liu, Jian
, p. 6622 - 6632 (2021/05/29)
A one-pot and step economic reaction involving Rh(III)-catalyzed C-H thiolation and relay Cu(II)-catalyzed C-N amination of acetanilide and 2-bromothiophenol is reported here, with several valuable phenothiazine products obtained. This synthesis protocol proceeds from easily starting materials, demonstrating high atom economy, broad substrate scope, and good yield. Furthermore, the directing group can be easily eliminated, and chlorpromazine is provided in a large scale; thus this synthesis protocol could be utilized to construct phenothiazine scaffolds.
The design and synthesis of an antibacterial phenothiazine-siderophore conjugate
Tarapdar, Abed,Norris, James K.S.,Sampson, Oliver,Mukamolova, Galina,Hodgkinson, James T.
supporting information, p. 2646 - 2650 (2018/11/03)
Siderophore-antibiotic conjugates consist of an antibiotic covalently linked by a tether to a siderophore. Such conjugates can demonstrate enhanced uptake and internalisation to the bacterial cell resulting in significantly reduced MIC values and extended spectrum of activity. Phenothiazines are a class of small molecules that have been identified as a potential treatment for multidrug resistant tuberculosis and latent TB. Herein we report the design and synthesis of the first phenothiazine-siderophore conjugate. A convergent synthetic route was developed whereby the functionalised phenothiazine component was prepared in four steps and the siderophore component also prepared in four steps. In M. smegmatis the functionalised phenothiazine demonstrated an equipotent MIC value in direct comparison to the parent phenothiazine from which it was derived. The final conjugate was synthesised by amide bond formation between the two components and global deprotection of the PMB protecting groups to unmask the catechol iron chelating groups of the siderophore. The synthesis is readily amenable to the preparation of analogues whereby the siderophore component of the conjugate can be modified. The route will be used to prepare a library of siderophore-phenothiazine conjugates for full biological evaluation of much needed new antibacterial agents.
Assembly of substituted phenothiazines by a sequentially controlled CuI/L-proline-catalyzed cascade C-S and C-N bond formation
Dawei, Ma.,Geng, Qian,Zhang, Hui,Jiang, Yongwen
supporting information; experimental part, p. 1291 - 1294 (2010/05/17)
(Chemical equation presented) In the pro-line of fire: A general and efficient cascade reaction approach to substituted phenothiazines, which relies on controlled sequential Cul/L-prolinecatalyzed C-S and C-N bond formations, is described. DMSO = dimethylsulfoxide.
