- Design, synthesis and anticancer activity of N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives
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Novel N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives were designed, synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR and Mass spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including K562, Colo-205 and MDA-MB 231 by MTT assay. The screening results showed that five compounds (16b, 16d, 16i, 16p and 16q) exhibited potent cytotoxic activities with IC50 values between 20 and 40 μM. Further in vitro studies revealed that inhibition of sirtuins could be the possible mechanism of action of these molecules.
- Gudisela, Mura Reddy,Srinivasu,Mulakayala, Chaitanya,Bommu, Praveen,Rao, M.V. Basaveswara,Mulakayala, Naveen
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- PROCESS FOR THE PREPARATION OF QUETIAPINE FUMARATE
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The present invention relates to an improved process for the preparation of quetiapine and pharmaceutically acceptable salts. It also relates to improved process for the preparation of intermediates of quetiapine.
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(2012/04/04)
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- PROCESS FOR THE PREPARATION OF QUETIAPINE FUMARATE
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The present invention relates to an improved process for the preparation of quetiapine and pharmaceutically acceptable salts. It also relates to improved process for the preparation of intermediates of quetiapine.
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(2010/09/18)
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- SYNTHESIS OF LL-(4-[2-(2-HYDROXYETHOXY)ETHYL]- PIPERAZINYL)DIBENZO[B,F][1,4]THIAZEPINE AND ITS FUMARATE SALT
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This invention broadly relates to a method for synthesizing ll-(4-[2-(2- hydroxyethoxy)ethyl]-piperazinyl)-dibenzo[b,f][l,4]thiazepine hemifumarate salt (Quetiapine hemifumarate) and the intermediate 11- piperazinyldibenzo[b,f][l,4]thiazepine dihydrochloride using phosphorous oxychloride in presence of non-aromatic solvent and condensing with piperazine.
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(2010/04/03)
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- An Improved and single pot process for the production of quetiapine hemifumarate substantially free from potential impurities
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An improved and single pot process for the preparation of Quetiapine hemifumarate (1), an antipsychotic drug, free from potential impurities is reported with an overall yield of 80%. The reported process for its preparation suffers from the drawback of producing potential impurities identified as 11-piperazin-1- yldibenzo[b,f][1,4]thiazepine (6), 2-(4-dibenzo[b,f][1,4] thiazepin-11- ylpiperazin-1-yl)ethanol (10), dimer (9), and N-methyl- Nphenyldibenzo[ b,f][1,4]thiazapine-11-amine (14). Elimination of these impurities in the process is achieved by chlorination of 3 followed by in situ condensation of obtained 4 with highly pure 8 and subsequently establishing the pH based workup to obtain free base 2, which is further converted to quetiapine hemifumarate salt free from all these impurities. In this report, different aspects of process development such as scheme selection, optimization of different process parameters, identification, synthesis, origin and control of impurities, and development of an accurate analytical method during the development of a scalable process for quetiapine hemifumarate are discussed.
- Niphade, Navnath C.,Mali, Anil C.,Pandit, Bhushan S.,Jagtap, Kunal M.,Jadhav, Sanjay A.,Jachak, Madhukar N.,Mathad, Vijayavitthal T.
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scheme or table
p. 792 - 797
(2010/04/22)
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- Identification, isolation, synthesis and characterization of impurities of quetiapine fumarate
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In the process for the preparation of quetiapine fumarate (1), six unknown impurities and one known impurity (intermediate) were identified ranging from 0.05-0.15% by reverse-phase HPLC. These impurities were isolated from crude samples using reverse-phase preparative HPLC. Based on the spectral data, the impurities were characterized as 2-[4-dibenzo[b,f][1,4]thiazepine-11-yl-1- piperazinyl]1-2-ethanol (impurity I, desethanol quetiapine), 11-[(N-formyl)-1-piperazinyl]-dibenzo[b,f][1,4]thiazepine (impurity II, N-formyl piperazinyl thiazepine), 2-(2-hydroxy ethoxy)ethyl-2-[2-[4-dibenzo[b,f][1,4] thiazepine-11-piperazinyl-1-carboxylate (impurity III, quetiapine carboxylate), 11-[4-ethyl-1-piperazinyl]dibenzo [b,f][1,4] thiazepine (impurity IV, ethylpiperazinyl thiazepine), 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1- piperazinyl)ethoxy]1-ethyl ethanol [impurity V, ethyl quetiapine), 1,4-bis[dibenzo[b,f][1,4]thiazepine-11-yl] piperazine [impurity VI, bis(dibenzo)piperazine]. The known impurity was an intermediate, 11-piperazinyl-dibenzo [b,f][1,4]thiazepine (piperazinyl thiazepine). The structures were established unambiguously by independent synthesis and co-injection in HPLC to confirm the retention times. To the best of our knowledge, these impurities have not been reported before. Structural elucidation of all impurities by spectral data (1H NMR, 13C NMR, MS and IR), synthesis and formation of these impurities are discussed in detail.
- Bharathi,Prabahar,Prasad,Srinivasa Rao,Trinadhachary,Handa,Dandala, Ramesh,Naidu
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- IMPROVED PROCESS FOR PREPARING QUETIAPINE FUMARATE
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Provided is an improved of quetiapine and pharmaceutically acceptable salts.
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(2008/12/04)
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- A PROCESS FOR THE PREPARATION OF 2-[2-(4-DIBENZO[b,f] [L,4] THIAZEPIN-11-yl-1- PIPERAZINYL)ETHOXY] ETHANOL FUMARATE
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A process for the preparation of 2-[2-(4-Dibenzo[b,f] [l,4] thiazepin-11-yl-1- ρiperazinyl)ethoxy] ethanol fumarate commonly known as Quetiapine hemifumarate. Dibenzo[b,f] [l,4] thiazepin-11-[10H]one is halogenated with a halogenating agent in the ratio of 1 : 0.5 to 3 w/v in an organic solvent in the presence of an organic base at reflux temperature followed by condensation of the reaction with piperazine without isolating the imino chloride. The piperazinyl-dibenzo[b,f] [l,4] thiazepine is converted to Quetiapine hemifumarate which is purified by crystallization with alcohol at reflux temperature and precipitated it by cooling the reaction mixture and recovered by filtration.
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(2010/11/25)
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- CRYSTALLINE FORMS
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The present invention is directed to a crystalline form the pharmaceutical compound 11-piperazin-1-yldibenzo[b,f][1,4]thiazepine as well as compositions, preparations, and pharmaceutical uses thereof.
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(2008/06/13)
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- PROCESS FOR THE PREPARATION OF 11-(4-[2-(2-HYDROXYETHOXY)ETHYL]-I-PIPERAZINYL)DIB ENZO[b,f][l,4]THIAZEPINE
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Disclosed is a process for the preparation of l l-(4-[2-(2-hydroxyethoxy)ethyl]-l- piperazinyl)-dibenzo[b,f][l,4]thiazepine. In the process, low-priced 2,2'-dithiosalicylic acid as starting material is subjected to bond formation reaction with l-chloro-2-
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(2010/02/15)
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- NEW USE OF 11-PIPERAZIN-1YLDIBENZO[B,F][1,4]THIAZEPINE OR ITS PHARMACEUTICALLY ACCEPTABLE SALT AND TO ORAL PHARMACEUTICAL COMPOSITIONS
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A method of treating at least one symptom or condition associated with but not limited to: 1) Substance-Related Disorders including but not limited to Substance Dependence, Substance Abuse, Substance Intoxication, Substance Withdrawal, Alcohol-Related Disorders, Amphetamine (or Amphetamine-Like)-Related Disorders, Caffeine-Related Disorders, Cannabis-Related Disorders, Cocaine-Related Disorders, Hallucinogen-Related Disorders, Inhalant-Related Disorders, Nicotine-Related Disorders, Opioid-Related Disorders, Phencyclidine (or Phencyclidine-Like)-Related Disorders, and Sedative-, Hypnotic-or Anxiolytic-Related Disorders. 2) Attention-Deficit and Disruptive Behavior Disorders. 3) Eating Disorders. 4) Personality Disorders including but not limited to Obsessive-Compulsive Personality Disorder. 5) Impulse-Control Disorders, comprising administering an effective amount of Formula I (I) or its pharmaceutically acceptable salt. In another aspect of the invention a pharmaceutical composition is provided comprising an effective amount of Formula I or its pharmaceutically acceptable salt and at least one pharmaceutically acceptable carrier or diluent.
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(2008/06/13)
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- SYNTHESIS OF 11-(4[-(2-HYDROXYETHOXY)ETHYL]-PIPERAZINYL)-DIBENZO[b,f][1,4]THIAZEPINE AND ITS FUMARATE SALT
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The invention is directed a method for synthesizing l l-(4-[2-(2- hydroxyethoxy)ethyl]-piperazinyl)-dibenzo[b,f] [l,4]thiazepine (quetiapine) and for recovering quetiapine as its fumarate salt in which dibenzo[b,f][l,4]thiazepine- l l(10H)one is chlorinated in the presence of a trialkyl amine base using a slight molar excess of phosphorous oxychloride to produce l l-chloro-dibenzo[b,f] [l,4]thiazepine which then is alkylated with piperazine to l l-piperazinyldibenzo[b,f] [l,4]thiazepine, which finally is alkylated with 2-(2-chloroethoxy)ethanol.
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Page/Page column 12
(2008/06/13)
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