- Design, synthesis, and molecular docking study of new piperazine derivative as potential antimicrobial agents
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Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis. All reported compounds were evaluated for their antibacterial and antifungal potential against five bacterial (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). The complete bacterial screening results are provided. As documented, piperazine derivative 3e performed the best against these bacteria. Additionally, data obtained during molecular docking studies are very encouraging with respect to potential utilization of these compounds to help overcome microbe resistance to pharmaceutical drugs, as explicitly noted in this manuscript.
- Patil, Mahadev,Noonikara Poyil, Anurag,Joshi, Shrinivas D.,Patil, Shivaputra A.,Patil, Siddappa A.,Bugarin, Alejandro
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supporting information
(2019/09/06)
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- Butyl methacrylate-co-ethylene glycol dimethacrylate monolith for online in-tube SPME-UHPLC-MS/MS to determine chlopromazine, clozapine, quetiapine, olanzapine, and their metabolites in plasma samples
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This manuscript describes a sensitive, selective, and online in-tube solid-phase microextraction coupled with an ultrahigh performance liquid chromatography-tandem mass spectrometry (in-tube SPME-UHPLC-MS/MS) method to determine chlopromazine, clozapine, quetiapine, olanzapine, and their metabolites in plasma samples from schizophrenic patients. Organic poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith was synthesized on the internal surface of a fused silica capillary (covalent bonds) for in-tube SPME. Analyte extraction and analysis was conducted by connecting the monolithic capillary to an UHPLC-MS/MS system. The monolith was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FTIR). The developed method presented adequate linearity for all the target antipsychotics: R2 was higher than 0.9975, lack-of-fit ranged from 0.115 to 0.955, precision had variation coefficients lower than 14.2%, and accuracy had relative standard error values ranging from ?13.5% to 14.6%, with the exception of the lower limit of quantification (LLOQ). The LLOQ values in plasma samples were 10 ng mL?1 for all analytes. The developed method was successfully applied to determine antipsychotics and their metabolites in plasma samples from schizophrenic patients.
- Beloti, Luiz G.M.,Miranda, Luis F.C.,Queiroz, Maria Eugênia C.
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- 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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p. 4140 - 4145
(2017/08/23)
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- Diversified synthesis of novel quinoline and dibenzo thiazepine derivatives using known active intermediates
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The novel drug development to control resisting infections in conventional drug therapy is a need of today. Few antiulcer relative derivatives developed by approaching convergent synthesis. The derivatives synthesized successfully are dibenzo thiazepine-pyridine (SLN11-SLN15) and benzimidazole-hydroquinoline based derivatives (SLN16-SLN20). It involved the coupling through microwave, sonication and conventional techniques at final step. The efficient technology identified as sonication technique basically time and yield. The reported compounds were structural characterized by elemental analysis and spectral studies such as 1H, 13C NMR and MS.
- Sharada,Satyanarayana Reddy,Sammaiah,Sumalatha
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p. 7959 - 7966
(2013/09/23)
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- DIBENZOTHIAZEPINE MODULATORS OF DOPAMINE, ALPHA ADRENERGIC, AND SEROTONIN RECEPTORS
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The present invention relates to new dibenzothiazepine modulators of D1 receptors, D2 receptors, alpha-1 adrenergic receptors, alpha-2 adrenergic receptors, H1 receptors, 5-HT1A receptors, and/or 5-HT2 receptors, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 26
(2010/04/23)
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- AMINO SUBSTITUTED DIARYL[A,D]CYCLOHEPTENE ANALOGS AS MUSCARINIC AGONISTS AND METHODS OF TREATMENT OF NEUROPSYCHIATRIC DISORDERS
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Disclosed herein are analogs of clozapine and pharmaceutically acceptable salts, esters, amides, or prodrugs thereof; methods of synthesizing the analogs; and methods of using the analogs for treating neuorpsychiatric disorders. In some embodiments, the analogs are amino substituted diaryl[a,d]cycloheptenes.
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Page/Page column 62
(2008/06/13)
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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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Page/Page column 13; 26-28
(2008/12/04)
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- DIBENZOTHIAZEPINE DERIVATIVES
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This invention relates to novel 11-[4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1- y1]dibenzo[b,f][1,4]thiazepine derivatives, their acceptable acid addition salts, solvates, hydrates and polymorphs thereof. The invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by antagonists of seratonergic 5HT1A and 5HT2 receptors, dopaminergic D1 and D2 receptor, histaminergic H1 receptors, and/or adrenergic αl and α2 receptors.
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Page/Page column 22
(2008/12/06)
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- Process for preparing quetiapine fumarate
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Provided is an improved synthesis of quetiapine and pharmaceutically acceptable salts.
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- SOLID FORMULATIONS
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The present invention is directed to solid formulations of the pharmaceutical compound 11-piperazin-l-yldibenzo[b,f][l,4]thiazepine as well as preparations, and pharmaceutical uses thereof
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Page/Page column 16-17
(2008/06/13)
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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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Page/Page column 13-14
(2008/06/13)
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- PROCESSES FOR THE PREPARATION OF THIAZEPINES
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The present invention relates to new processes for the preparation of thiazepines and of salts thereof. Specifically the present invention provides simple one-pot processes for the preparation of thiazepines. The invention further relates to the use of essentially the same inert solvent or of a mixture of inert solvents for the preparation of thiazepines and salts thereof, to the use of an about equimolar amount of a starting material and a halogenating agent for the preparation of thiazepines and to compositions useful in the process of the invention.
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Page/Page column 13-15
(2008/06/13)
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- A PROCESS FOR THE PREPARATION OF AN 11-(4-SUBSTITUTED-I-PIPERAZINYL)DIBENZO[b,f][1,4]THIAZEPINE DERIVATIVE
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A process for the preparation of an 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine derivative, of general Formula (I), where A is hydrogen or a -(CH2)2-OH group or a -(CH2)2-0-(CH2)2-OH group, or of a salt thereof, comprises a step in which 10H-dibenzo[b,f][1,4]thiazepin-11-one is reacted with a piperazine derivative in the presence of a titanium alkoxide of general formula Ti(OR)4, where R is a straight or branched alkyl group, having from one to eight carbon atoms to obtain said Formula I derivative or a salt thereof. Where A is -(CH2)2-0-(CH2)2-OH, then the piperazine derivative is 1-(2-(2-hydroxyethoxy)ethyl)piperazine and the 11-(4-substituted-1-piperazinyl)dibenzo[b,f][1,4]thiazepine is quetiapine, (11-(4-(2-(2-hydroxyethoxy)ethyl)-1-piperazinyl)dibenzo[b,f][1,4]thiazepine). The process may comprise an additional step of reacting the quetiapine with fumaric acid to obtain quetiapine hemifumarate.
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Page/Page column 16-17
(2008/06/13)
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- USE OF N-DESMETHYLCLOZAPINE AND RELATED COMPOUNDS AS DOPAMINE STABILIZING AGENTS
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Disclosed herein is the use of N-desmethylclozapine (NDMC) and related compounds to treat a variety of neuropsychiatric diseases including psychosis. It is shown that NDMC and related compounds are agonists or partial agonists at D2 and D3 dopamine receptors and thus may be effective as a dopamine stabilizing agent, allowing it to be used to treat or provide reduced incidence of Extrapyramidal symptoms (EPS) and/or tardive dyskinesias (TD). Also disclosed is administering NDMC and related compounds in combination with other anti-psychotic agents.
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Page/Page column 77-78
(2010/11/24)
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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 13
(2008/06/13)
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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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Page/Page column 10-11
(2008/06/13)
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- PROCESS FOR PRODUCING 11-[4-[2-(2-HYDROXYETHOXY)ETHYL]-1-PIPERAZINYL]DIBENZO[b,f][1,4]THIAZEPINE AND A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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A process for producing 11-[4-[2-(2-hydroxyethoxy)ethyl]-l-piperazinyl]dibenzo [b,f][1,4]thiazepine [I] and a pharmaceutically suitable acid addition salt is disclosed. Accordingly, thiosalicylic acid [XVI] is reacted with o-halonitrobenzene [XVII] using a phase transfer catalyst to obtain 2-nitro-2'-carboxydiphenylsulphide [XI]. It is hydrogenated in the presence of a noble metal catalyst to obtain 2-amino-2' carboxydiphenyl sulphide [X]. The 2-amino-2'-carboxydiphenylsulphide [X] is reacted with halide or oxyhalide of the phosphorous to obtain in situ iminohalide [VI], which further reacts as such with 1-hydroxyethoxyethylpiperazine or condenses with piperazine to obtain 11-piperazinyldi.benzo[b,f][1,4]thiazepine [XIX] which further reacts with 2- chloroethoxyethanol or reacts with 1-(2-hydroxyethyl)piperazine to give 11-[4-(2-hydroxyethyl)piperazine-1-yl]dibenzo[b,f][ 1,4]thiazepine [XXXI] which further converts to an intermediate 11-[4-(2-substitutedethyl)piperazin-1- yl)dibenzo[b,f][1,4]thiazepine wherein the substituent at the 2-position is selected from mesyloxy or tosyloxy or halo group [XXXII] followed by reaction with ethylene glycol to give quetiapine [1].
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Page/Page column 9; 16
(2008/06/13)
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- AMINO SUBSTITUTED DIARYL[A,D]CYCLOHEPTENE ANALOGS AS MUSCARINIC AGONISTS AND METHODS OF TREATMENT OF NEUROPSYCHIATRIC DISORDERS
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Disclosed herein are analogs of clozapine and pharmaceutically acceptable salts, esters, amides, or prodrugs thereof; methods of synthesizing the analogs; and methods of using the analogs for treating neuorpsychiatric disorders. In some embodiments, the analogs are amino substituted diaryl[a,d]cycloheptenes.
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Page/Page column 59-60
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF 11-(1-PIPERAZINYL)DIBENZO `B, F! `1 ,4!-THIAZEPINE, AN INTERMEDIATE IN THE SYNTHESIS OF THE ANTIPSYCHOTIC DRUG QUETIAPINE
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A process for the preparation of 11-(1-piperazinyl)dibenzo-[b, f ] [ 1, 4 ] thiazepine comprising reacting phenyl 2-(phenylthio) phenylcarbamate with piperazine and cyclizing the obtained N-[ (2 -phenylthio) phenyl ] -1 -piperazinylcarboxamide in a presence of cyclizing agent. 11-(1-piperazinyl)-dibenzo [b, f] [1, 4]thiazepine is itself, an intermediate in the synthesis of antipsychotic drug Quetiapine.
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Page/Page column 6-8; 12
(2008/06/13)
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- NOVEL DIBENZOTHIAZEPINE ANTIPSYCHOTIC
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11-[4-[2-(2-Hydroxyethoxy)ethyl]-1-piperazinyl]dibenzo[b,f][1, 4 ] thiazepine is disclosed as a neuroleptic with a much reduced incidence of side effects such as acute dystonia and dyskinesia and tardive diskinesia.
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- Process for the preparation of a thiazepine compound
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11-(4-[2-(2-Hydroxyethoxy)ethyl]-piperazinyl)-dibenzo[b,f][1,4]thiazepine and the salts thereof possess antiandropaninergic activity, especially antipyschotic activity, and are prepared by reacting 11-piperazinyldibenzo[b,f][1,4]thiazepine with a compound of the formula:-, X-CH2-CH2-O-CH2-CH2OH, (wherein X represent an atom or group removable as an anion and, where appropriate further reaction of the product obtained to yield the free base or salt as desired.
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