16189-69-8

Usage

Uses

Used in Pharmaceutical Industry:
2-Chloro-10-(chloroacetyl)-10H-phenothiazine is used as an intermediate in the synthesis of various pharmaceuticals and organic compounds. Its unique structure with two chlorine atoms and a chloroacetyl group allows for the development of new drugs with potential therapeutic benefits.
Used in Research and Development:
2-Chloro-10-(chloroacetyl)-10H-phenothiazine is also used in research and development for exploring its potential biological and pharmacological activities. As its specific uses and applications are still being investigated, it serves as a valuable compound for scientists to study and understand its properties and possible applications in medicine and other fields.

InChI:InChI=1/C14H9Cl2NOS/c15-8-14(18)17-10-3-1-2-4-12(10)19-13-6-5-9(16)7-11(13)17/h1-7H,8H2

Upstream product

• 92-39-7 2-chlorophenothiazine 
• 79-04-9 chloroacetyl chloride 
• 101-17-7 3-chlorodiphenylamine 

Downstream Products

• 96761-99-8 2-chloro-10-[(2,4,6-trioxo-5-phenyl-hexahydro-pyrimidin-5-yl)-acetyl]-10H-phenothiazine 
• 1204531-55-4 1-[2-(2-chloro-10H-phenothiazin-10-yl)-2-oxoethyl]-1H-pyrrole-2,5-dione 
• 1204531-52-1 1-[2-(2-chloro-10H-phenothiazin-10-yl)-2-oxoethyl]pyrrolidine-2,5-dione 
• 17210-75-2 2-chloro-10-(2'-chloroethyl)-10H-phenothiazine 
• 1423077-61-5 4-trifluoromethoxy-N-(2-(2-chloro-10H-phenothiazin-10-yl)ethyl)benzenesulfonamide 
• 86224-76-2 8-Chlorbutaperazin 
• 86224-77-3 8-Chlorbutaperazinoxalat 
• 86209-69-0 <8-3H>Butaperazin 
• 904317-69-7 1-(2-chloro-phenothiazin-10-yl)-2-(6,7-dimethoxy-1-methyl-3,4-dihydro-1H-isoquinolin-2-yl)ethanone 

Relevant academic research and scientific papers

An Inhibitor of the Interaction of Survivin with Smac in Mitochondria Promotes Apoptosis

Herein we report the first small molecule that disrupts the survivin-Smac interaction taking place in mitochondria. The inhibitor, PZ-6-QN, was identified by initially screening a phenothiazine library using a fluorescence anisotropy assay and then conducting a structure–activity relationship study. Mutagenesis and molecular docking studies suggest that PZ-6-QN binds to survivin similarly to the known Smac peptide, AVPI. The results of the effort also show that PZ-6-QN exhibits good anticancer activity against various cancer cells. Moreover, cell-based mechanistic studies provide evidence for the proposal that PZ-6-QN enters mitochondria to inhibit the survivin-Smac interaction and promotes release of Smac and cytochrome c from mitochondria into the cytosol, a process that induces apoptosis in cancer cells. Overall, the present study suggests that PZ-6-QN can serve as a novel chemical probe for study of processes associated with the mitochondrial survivin-Smac interaction and it will aid the discovery of novel anticancer agents.

Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase

A number of phenothiazine-, phenoxazine- and related tricyclics-derived chloroacetamides were synthesized and evaluated in vitro for antiprotozoal activities against Leishmania major (L. major) promastigotes. Several analogs were remarkably potent inhibitors, with antileishmanial activities being comparable or superior to those of the reference antiprotozoal drugs. Furthermore, we explored the structure-activity relationships of N-10 haloacetamides that influence the potency of such analogs toward inhibition of L. major promastigote growth in vitro. With respect to the mechanism of action, selected compounds were evaluated for time-dependent inactivation of Trypanosoma brucei trypanothione reductase. Our results are indicative of a covalent interaction which could account for potent antiprotozoal activities.

Phenothiazines nitric oxide donor, its preparation and use

The invention discloses a kind of phenothiazine-containing nitric oxide donor compounds with the structure of a formula I. In the formula I, n is equal to 0, 1 or 2, R1 is hydrogen, halogens, C1-C4 branched or linear alkyl, or halogenated C1-C4 branched or linear alkyl, and R2 is hydrogen or C1-C4 branched or linear alkyl. The invention also discloses a preparation method of the compounds, and discloses a pharmaceutical composition taking the compounds as an active composition, and application of the compounds as anti-tumor medicines, especially to prepare medicines for treating breast cancer, lung cancer and stomach cancer.

Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents

A new library of phenothiazine and 1,3,4-thiadiazole hybrid derivatives (5a-u) was designed based on the molecular hybridization approach and the molecules were synthesized in excellent yields using a facile single-step chloro-amine coupling reaction between 2-chloro-1-(10H-phenothiazin-10-yl)ethanones and 2-amino-5-subsituted-1,3,4-thiadiazoles. The compounds were evaluated for their in vitro inhibition activity against Mycobacterium tuberculosis H37Rv (MTB). Compounds 5g and 5n were emerged as the most active compounds of the series with MIC of 0.8 μg/mL (～1.9 μM). Also, compounds 5a, 5b, 5c, 5e, 5l and 5m (MIC = 1.6 μg/mL), and compounds 5j, 5k and 5o (MIC = 3.125 μg/mL) showed significant inhibition activity. The structure-activity relationship demonstrated that an alkyl (methyl/npropyl) or substituted (4-methyl/4-Cl/4-F) phenyl groups on the 1,3,4-thiadiazole ring enhance the inhibition activity of the compounds. The cytotoxicity study revealed that none of the active molecules are toxic to a normal Vero cell line thus proving the lack of general cellular toxicity. Further, the active molecules were subjected to molecular docking studies with target enzymes InhA and CYP121.

Reengineered tricyclic anti-cancer agents

The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling.

TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS

Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of phenothiazine, dibenzoazepine and annulene and similar genera.

New farnesyltransferase inhibitors in the phenothiazine series

The biological screening of the chemical library of our Organic Chemistry Department, carried out on an automated fluorescence-based FTase assay, allowed us to discover that a phenothiazine derivative (1d) was an inhibitor of farnesyltransferase. Three new series of human farnesyltransferase inhibitors, based on a phenothiazine scaffold, were synthesized with protein farnesyltransferase inhibition potencies in the low micromolar range. Ester derivative 9d was the most active compound in these series. Four synthesized compounds were evaluated for their antiproliferative activity on a NCI-60 cancer cell line panel. The modest results obtained in this preliminary investigation showed that mixing the phenothiazine and the 1,2,3-triazole motif in the structure of a single compound can lead to new scaffolds in the field of farnesyltransferase inhibitors.

Synthesis and antimicrobial activity of some new N-acyl substituted phenothiazines

A series of 2-substituted N-acylphenothiazines were synthesized by using imides, N-carboxymethyl imides and the structures of these newly synthesized compounds were confirmed by spectral and elemental analyses. All new compounds were tested for their antibacterial and antifungal activities. Some compounds showed promising antibacterial and antifungal activities.

N-Homolupinanoyl and N-(ω-lupinylthio)alkanoyl derivatives of some tricyclic systems as ligands for muscarinic M1 and M2 receptor subtypes

A set of N-homolupinanoyl- and N-(ω-lupinylthio)alkanoyl derivatives of tricyclic systems (as phenothiazine, iminodibenzyl and dihydropyridobenzodiazepinone) has been prepared and tested for affinity for rat muscarinic M1 and M2 receptor subtypes labeled with [3H]pirenzepine and [3H]AF-DX 384. Good affinity for both M1 and M2 subtypes was displayed by most compounds, often with nanomolar Ki values, which for lupinylthiopropionyl- and lupinylthiobutyryl-phenothiazines (13-16) were comparable to those of pirenzepine and methoctramine, respectively. However, only moderate selectivity for one or the other subtype was seen.