58-40-2

Usage

Uses

Used in Psychiatric Practice:
Promazine is used as an antipsychotic and tranquilizer for minor cases of psychomotor excitement in schizophrenics, paranoid and manic-depressive conditions, neurosis, alcoholic psychosis, and other psychiatric conditions.
Used in Anesthesiological Practice:
Promazine is sometimes utilized in anesthesiological practice, where its antipsychotic and tranquilizing properties can be beneficial.

Synthesis

Promazine, 10-(3-dimethylaminopropyl)phenothiazine (6.1.1), is prepared by the alkylation of phenothiazine with 3-dimethylaminopropylchloride in the presence of sodium amide [1–3].

InChI:InChI=1/C17H20N2S/c1-18(2)12-7-13-19-14-8-3-5-10-16(14)20-17-11-6-4-9-15(17)19/h3-6,8-11H,7,12-13H2,1-2H3

Upstream product

• 39743-22-1 p-toluenesulfonic acid 3-dimethylamino-n-propyl ester 
• 92-84-2 10H-phenothiazine 
• 109-54-6 3-(Dimethylamino)propyl chloride 
• 50-00-0 formaldehyd 
• 2095-21-8 3-(10H-phenothiazin-10-yl)propan-1-amine 
• 5909-59-1 10-(3-chloropropyl)-10H-phenothiazine 
• 124-40-3 dimethyl amine 
• 69-09-0 chlorpromazine hydrochloride 
• 72331-95-4 Phenothiazine-10-carboxylic acid 3-dimethylamino-propyl ester 
• 18956-87-1 10H-phenothiazine-10-carbonyl chloride 
• 583-55-1 1-Bromo-2-iodobenzene 
• 6320-02-1 o-bromothiophenol 
• 109-55-7 1-amino-3-(dimethylamino)propane 
• 583-53-9 2,3-dibromobenzene 

Downstream Products

• 581-30-6 3H-Phenothiazin-3-one 
• 1207-71-2 sulfoxyde de phenothiazine 
• 146-21-4 promazine sulfoxide 
• 50-00-0 formaldehyd 
• 38076-67-4 10H-phenothiazine-10-carbaldehyde 
• 92-84-2 10H-phenothiazine 
• 2095-20-7 Norpromazine 
• 68-12-2 N,N-dimethyl-formamide 
• 17140-12-4 N-methyl-10H-phenothiazine-10-propanamine hydrochloride 
• 22541-69-1 plutonium (5+) 
• 103757-58-0 N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methyl-3-phenothiazin-10-ylpropan-1-amine 

Relevant academic research and scientific papers

A visible-light-photocatalytic water-splitting strategy for sustainable hydrogenation/deuteration of aryl chlorides

Hydrogenation/deuteration of carbon chloride (C?Cl) bonds is of high significance but remains a remarkable challenge in synthetic chemistry, especially using safe and inexpensive hydrogen donors. In this article, a visible-light-photocatalytic watersplitting hydrogenation technology (WSHT) is proposed to in-situ generate active H-species (i.e., Had) for controllable hydrogenation of aryl chlorides instead of using flammable H2. When applying heavy water-splitting systems, we could selectively install deuterium at the C?Cl position of aryl chlorides under mild conditions for the sustainable synthesis of high-valued added deuterated chemicals. Sub-micrometer Pd nanosheets (Pd NSs) decorated crystallined polymeric carbon nitrides (CPCN) is developed as the bifunctional photocatalyst, whereas Pd NSs not only serve as a cocatalyst of CPCN to generate and stabilize H (D)-species but also play a significant role in the sequential activation and hydrogenation/deuteration of C?Cl bonds. This article highlights a photocatalytic-WSHT for controllable hydrogenation/deuteration of low-cost aryl chlorides, providing a promising way for the photosynthesis of high-valued added chemicals instead of the hydrogen evolution.

A Focused Library of Psychotropic Analogues with Neuroprotective and Neuroregenerative Potential

Overcoming the lack of effective treatments and the continuous clinical trial failures in neurodegenerative drug discovery might require a shift from the prevailing paradigm targeting pathogenesis to the one targeting simultaneously neuroprotection and neuroregeneration. In the studies reported herein, we sought to identify small molecules that might exert neuroprotective and neuroregenerative potential as tools against neurodegenerative diseases. In doing so, we started from the reported neuroprotective/neuroregenerative mechanisms of psychotropic drugs featuring a tricyclic alkylamine scaffold. Thus, we designed a focused-chemical library of 36 entries aimed at exploring the structural requirements for efficient neuroprotective/neuroregenerative cellular activity, without the manifestation of toxicity. To this aim, we developed a synthetic protocol, which overcame the limited applicability of previously reported procedures. Next, we evaluated the synthesized compounds through a phenotypic screening pipeline, based on primary neuronal systems. Phenothiazine 2Bc showed improved neuroregenerative and neuroprotective properties with respect to reference drug desipramine (2Aa). Importantly, we have also shown that 2Bc outperformed currently available drugs in cell models of Alzheimer's and Parkinson's diseases and attenuates microglial activation by reducing iNOS expression.

NB 06: From a simple lysosomotropic aSMase inhibitor to tools for elucidating the role of lysosomes in signaling apoptosis and LPS-induced inflammation

Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli-induced increase of C16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis. Compounds like NB 06 thus offer highly interesting fields of application besides prevention of apoptosis of macrophages in atherosclerotic plaques in vessel walls. Most importantly, they can be used for blocking pH-dependent lysosomal processes and enzymes in general as well as for analyzing lysosomal dependent cellular signaling. Modulation of gene expression of several prominent inflammatory messengers IL1B, IL6, IL23A, CCL4 and CCL20 further indicate potentially beneficial effects in the field of (systemic) infections involving bacterial endotoxins like LPS or infections with influenza A virus.

Preparation and electrochemical behavior of N-substituted phenothiazine oxide

The chemical properties of promazine oxide (Prom-O) and promazine (Prom) were compared. Cyclic voltammetry (CV) experiments showed a higher oxidation potential of Prom-O compared to that of Prom. The results of CV measurements also suggested the potential applicability of Prom-O as an n-type semiconductor.

A mechanistic study on the disproportionation and oxidative degradation of phenothiazine derivatives by manganese(III) complexes in phosphate acidic media

The oxidative degradation of phenothiazine derivatives (PTZ) by manganese(III) was studied in the presence of a large excess of manganese(III)-pyrophosphate (P2O7 2-), phosphate (PO4 3-), and H+ ions using UV-vis. spectroscopy. The first irreversible step is a fast reaction between phenothiazine and manganese pyrophosphate leading to the complete conversion to a stable phenothiazine radical. In the second step, the cation radical is oxidized by manganese to a dication, which subsequently hydrolyzes to phenothiazine 5-oxide. The reaction rate is controlled by the coordination and stability of manganese(III) ion influenced by the reduction potential of these ions and their strong ability to oxidize many reducing agents. The cation radical might also be transformed to the final product in another competing reaction. The final product, phenothiazine 5-oxide, is also formed via a disproportionation reaction. The kinetics of the second step of the oxidative degradation could be studied in acidic phosphate media due to the large difference in the rates of the first and further processes. Linear dependences of the pseudo-first-order rate constants (k obs) on [Mn III] with a significant non-zero intercept were established for the degradation of phenothiazine radicals. The rate is dependent on [H+] and independent of [PTZ] within the excess concentration range of the manganese(III) complexes used in the isolation method. The kinetics of the disproportionation of the phenothiazine radical have been studied independently from the further oxidative degradation process in acidic sulphate media. The rate is inversely dependent on [PTZ+.], dependent on [H+], and increases slightly with decreasing H+ concentration. Mechanistic consequences of all these results are discussed.

Photodegradation of 2-chloro substituted phenothiazines in alcohols

The mechanisms that trigger the phototoxic response to 2- chlorophenothiazine derivatives are still unknown. To better understand the relationship between the molecular structure of halogenated phenothiazines and their phototoxic activity, their photophysics and photochemistry were studied in several alcohols. The photodestruction quantum yields were determined under anaerobic conditions using monochromatic light (313 nm). Absorption- and emission-spectroscopy, 1H- and 13C-NMR and GC-MS were used to characterize the photoproducts and reference compounds. An electron transfer mechanism had been previously proposed by Bunce et al. (J. Med. Chem. 22, 202-204) to explain the large difference between the photodestruction quantum yield of 2-chlorpromazine (φ = 0.46) and 2-chlorphenothiazine (φ = 0.20). According to these authors, the alkylamino chain transfers an electron to the phenothiazine moiety. Our results demonstrate that this mechanism is incorrect, because the photodestruction quantum yields of all chlorinated derivatives of this study are the same under the same conditions of solvent and irradiation wavelength. The quantum yield has no dependence on the 10-substituent, but it depends on the solvent. The percentage of each photoproduct, on the other hand, strongly depends on that substituent, but not very much on the solvent. Finally, it is demonstrated that the phototoxic effect of chlorinated phenothiazines is not related to the photodechlorination, although both processes share the same transient.

Palladium-catalyzed three-component approach to promazine with formation of one carbon-sulfur and two carbon-nitrogen bonds

(Chemical Presented) Zip it up! The use of a Pd/dppf catalyst gives access to the tricyclic phenothiazine scaffold starting from 1-bromo-2-iodobenzenes, aliphatic or aromatic amines, and 2-bromothiophenols in a single reaction flask (see scheme; dppf=1,1′-bis(diphenylphosphanyl) ferrocene; dba=dibenzylidineacetone). This transformation involves thioether formation and subsequent intermolecular and intramolecular aryl amination reactions. The reaction occurs in good overall yield and selectivity.

Pd/C-Et3N-mediated catalytic hydrodechlorination of aromatic chlorides under mild conditions

A mild and efficient one-pot procedure for the hydrodechlorination of aromatic chlorides using a Pd/C-Et3N system was developed. A variety of aromatic chlorides could be dechlorinated at room temperature and under ambient hydrogen pressure. Et3N activates the catalysis and is likely to work as a single electron donor in this system.

Photochemistry in Micelles as a Model for the in vivo Phototoxicity of Chlorpromazine

The photochemical reactivity of chlorpromazine has been studied in an oxygenated solution containing micelles.The photochemical dehalogenation reaction which had previously only been observed in oxygen-free solutions was found to predominate.The relevance of this photoreaction and the micelle as a model for the in vivo phototoxicity of chlorpromazine is discussed.