- Phenothiazine compound as well as preparation method and application thereof
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The invention discloses a phenothiazine compound which has the advantages of novel structural general formula and framework, high efficiency, low toxicity and better inhibitory activity on LSD1. The invention also discloses a preparation method of the compound. The preparation method has the characteristics of mild reaction conditions, simplicity in operation and high reaction yield. According to the invention, phenothiazine is taken as a raw material, active groups are respectively introduced to a parent of phenothiazine, and new phenothiazine pharmacophores are synthesized; and phenothiazine compounds are designed and synthesized by modification with piperazine, morpholine, piperidine and other groups. The compound retains the activity of phenothiazine and also has the characteristics of modification groups, so that the biological activity of original molecules is improved, and the anti-tumor activity of target molecules is improved. The invention also discloses an application of the compound in preparation of LSD1-targeted antitumor drugs, and the compound shows good inhibitory activity on LSD1 and shows good development potential.
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Paragraph 0041-0042; 0045-0046; 0047-0050
(2021/08/19)
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- Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
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The neuroleptic drug thioridazine has been recently repositioned as possible anti-tubercular drug. Thioridazine showed anti-tubercular activity against drug resistant mycobacteria but it is endowed with adverse side effects. A small library of thioridazine derivatives has been designed through the replacement of the piperidine and phenothiazine moieties, with the aim to improve the anti-tubercular activity and to reduce the cytotoxic effects. Among the resulting compounds, the indole derivative 12e showed an antimycobacterial activity significantly better than thioridazine and a cytotoxicity 15-fold lower.
- Scalacci, Nicolò,Brown, Alistair K.,Pavan, Fernando R.,Ribeiro, Camila M.,Manetti, Fabrizio,Bhakta, Sanjib,Maitra, Arundhati,Smith, Darren L.,Petricci, Elena,Castagnolo, Daniele
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p. 147 - 158
(2016/12/30)
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- Synthesis and biochemical characterization of new phenothiazines and related drugs as MDR reversal agents
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Chemotherapy is one of the most important methods in the treatment of cancer. However, development of drug resistance during chemotherapy is the leading cause of treatment failure and decreased survival in cancer patients. Multidrug resistance (MDR) is one of the extensively studied forms of drug resistance for more than 30 years. The members of ATP-binding cassette protein family are responsible for multidrug resistance with P-glycoprotein as most representative transporter. To overcome multidrug resistance, pharmacological modulation of the transporters by efflux pump inhibitors seem to be the first choice, but preclinical studies did not lead to clinical applications. Therefore, a systematical research for pharmacophor structures is a promising strategy to increase the efficacy of those drugs still influencing multidrug resistance. In this study a range of phenothiazine derivatives was synthesizied with systematical variation of three molecule domains. The biochemical determination of multidrug resistance reversal activity was achieved with the crystalviolet assay on LLC-PK1/MDR1 cells. The results will be discussed considering of hypotheses in the literature directed to new structure-acitivity relationships to overcome drug resistance in the future.
- Schmidt, Matthias,Teitge, Marlen,Castillo, Marianela E.,Brandt, Tobias,Dobner, Bodo,Langner, Andreas
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experimental part
p. 624 - 638
(2009/04/06)
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- Synthesis of phenothiazine derivatives as potential inhibitors of phospholipase C
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In order to study the structure-activity relationships of phenothiazine derivatives inhibiting phosphatidylinositol-specific phospholipase C (PI-PLC), the synthesis of some phenothiazine amide, amine and ester derivatives was performed mainly by reacting 10H-phenothiazine-10-propanoyl chloride with some amines and alcohols; the resulting amides were reduced with borane to yield the corresponding amines. Starting from 2-chloro and 2-trifuoromethyl-10H-phenothiazine-10-propanoyl chloride two amides were synthesized. The inhibiting activity on PI-PLC from human platelets is reported.
- Brufani,Cesta,Filocamo,Lappa,Marta,Pomponi,Meroni,Pagella
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p. 585 - 597
(2007/10/02)
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- Synthesis of Perazine
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A novel synthesis of perazine (10-(4-methylpiperazinyl-3-propyl)phenothiazine), likely to be applicable to 10-dialkylaminopropyl phenothiazines generally, is described.
- Owen, Terence C.
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p. 265 - 266
(2007/10/02)
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