Efficieant synthesis of 1, 5 benzothiazepine derivatives using benzyl tri ethyl ammonium chloride in ethonol l. The first molecule of 1, 5 benzothiazepine used clinically was diltiazem 6, followed by clentiazem 7, for their cardiovascular action. Synthesis of some novel 1, 5benzothiazepine derivatives. Claisenschmidt condensation of h ydroxyacetophenone with di erent substituted aldehydes and oaminothiopheno. Selective peripheraltype benzodiazepine receptor pbr ligands, such as pk 11195 and ro 54864, have recently been found to possess low but significant inhibitory activity of ltype calcium channels, and this property is implicated in the. To control tachycardia, diltiazem is also given after antithyroid therapy in such patient where. Pdf synthesis and biological evaluation of 5hindolo 3. In this paper, we have presented results of 2d, and 3d docking poses studies of a series of 300 three series molecules containing 1, 5 benzothiazepine pharmacophore as anticonvulsant agents. A mouse model of atypical antipsychoticassociated adverse effects was used to compare the liability to induce weight gain, food intake, and metabolic alterations after chronic olanzapine ol. Both the benzothiazepines and chalcones were evaluated as dpph free.
The newly synthesized compounds 4ag were screened for in vivo antiinflammatory activity at a dose of 10 mgkg bw. The synthesis and cardiovascular characterization of a series of novel pyrrolo2,1d1,5benzothiazepine derivatives 54. Improved method for the synthesis of new 1, 5 benzothiazepine derivatives as analogues of anticancer drugs by anoop k. R 1 r 1 r 1 r 2 r 2 ch 3 ch 3 nh 2 nh 2 solid phase synthesis of 3 hydroxy2,3dihydro 1, 5 benzothiazepines 9a p hmeoh, ring b ring b s. Improved method for the synthesis of new 1, 5 benzothiazepine derivatives as analogues of anticancer drugs. Reg1117 reg1117a 800ma and 1a low dropout positive. Improved method for the synthesis of new 1,5benzothiazepine. M, respectively named compound a in this study figure 1 27. A key intermediate of diltiazem synthesis, 2s,3s2,3dihydro3hydroxy24methoxyphenyl 1, 5 benzothiazepin45hone 2s,3s 1, has been efficiently synthesized by an asymmetric reduction of the prochiral ketone, 24methoxyphenyl 1, 5 benzothiazepine 3,42h,5hdione 3, with nabh4 and chiral. It belongs to the benzothiazepine group of calcium channel blockers. Syntheses of some new 1, 5 benzothiazepine derivatives and their ribofuranosides as antimicrobial agents.
Ir spectra are recorded using kbr discs on 8400s ftir shimadzu. Benzothiazepine c9h7ns cid 17929084 structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities. Asian journal of pharmaceutical analysis and medicinal. Synthesis and antimicrobial screening of new chalcones and 1, 5 benzothiazepines containing quinoline nucleus. Thiazepines are substituted thiepins, with a nitrogen replacing a carbon in the sevenmembered heterocyclic compound. Specifically 1, 5 substituted benzothiazepine 19 are well known compounds for diverse therapeutically properties like antimicrobial 20, antihypertensive 21, calcium channel blocker 22, blood platelet aggregation inhibitory. Synthesis of various 1,5benzothiazepine derivatives from.
Novel 1, 5benzothiazepine derivatives were synthesized and characterized by spectral studies. Substituted chalcones 1 were reacted with 2aminothiophenol 2 to give 1, 5 benzothiazepine derivatives 3aj. Novel 1, 5 benzothiazepine derivatives were synthesized and characterized by spectral studies. Jntuk, kakinada 5330032department of pharmaceutical.
Synthesis of 1,5benzothiazepine derivatives bearing 2. We present the binding data for 1, 5 benzothiazepine derivatives with g6ps in this report. Synthesis of halogensubstituted 1,5benzothiazepine. The fragmentation pattern of 18 may be represented as in scheme 1169.
From dual pbr affinity and calcium antagonist activity to novel and selective calcium entry blockers. Journal of chemical and pharmaceutical research, 2016, 81. The availability of several cocrystallized structures for both ches with different. A series of 1, 5 benzothiazepine derivatives were synthesized by the reaction of 1, 5 benzothiazepine containing 2phenoxyquinoline with benzohydroximinoyl chlorides and hydrazonoyl chlorides at room temperature. With this in mind, some new 1, 5 benzothiazepine derivatives have been synthesized in search of better therapeutic agents, by a convenient single pot method. Derivatives of 1, 5 benzothiazepines are of particular. Over the years the portable document format has evolved enormously. Quetiapine,19 possess 1, 5 benzothiazepine skeletons. Because of their interesting biological properties, functionalized 1, 5 benzothiazepin45hones represent an important class of heterocyclic compounds. Synthesis of various 1, 5 benzothiazepine derivatives from 1 44methyl piperazinyldiazenylphenyl3substitutedphenylprop2en 1 one and studies of their antimicrobial activity shailesh j. Syntheses and biological activities of chalcone and 1,5.
Introduction the 1, 5 benzothiazepine is one of the three possible benzocondensed derivatives, viz. G6ps is a known target for antibacterial and antifungal infections. Recently, synthesis and a biological evaluation of thiazepine from. The parent 1,5benzothiazepine, 1, itself has not hitherto been described in the literature for its pharmacological properties. Diltiazem is extensively used as antianginal and antiarrhythmic drug. Docking analysis was utilized to predict the mechanism of action of the designed derivatives for anticonvulsant potential. Cardiovascular characterization of pyrrolo2, 1 d 1, 5 benzothiazepine derivatives binding selectively to the peripheraltype benzodiazepine receptor pbr. The various reported methodologies involve the use of inorganic solid supports such as alumina, silica gel and clay under microwave irradiation, acetic acid or trifluoroacetic acid, hydrochloric. This data should be further evaluated using in vitro and in vivo studies for safety, activity, efficacy and toxicity. The 1 1 hydroxynaphthalene2ylethanone obtained is then heated with aromatic aldehyde using ethanol as a solvent and 40% koh which on condensation gave 1. This page lists all the major releases, starting from pdf 1.
Certain pdf documents may only be viewed in newer versions of acrobat. The first molecule of 1, 5 benzothiazepine used clinically was. In silico modeling of the specific inhibitory potential of. Research open access in silico modeling of the specific. Synthesis of novel coumarin derivatives and its biological.
Synthesis, antimicrobial and antifungal study of 2,4. Apr 25, 2011 modulation of constitutive androstane receptor car and pregnane x receptor pxr by 6arylpyrrolo2, 1 d 1, 5 benzothiazepine derivatives, ligands of peripheral benzodiazepine receptor pbr linnea e. Benzothiazepines constitute valuable structural units in the field of pharmaceutical research. Inspired with the biological profile of 1, 5 benzothiazepine and benzofuran derivatives, in continuation of our work on biologically active heterocycles 3245, and in order to know the combined effect of both 1, 5 benzothiazepine and benzofuran on biological activity, it was considered worth. The 1, 5 benzothiazepine derivatives are of particular interest for lead discovery because they have been found active against different families of targets 1424. Synthesis of various 1,5benzothiazepine derivatives from 1. Synthesis and biological study of novel methylenebis.
Depending on the location of the nitrogen, one distinguishes 1,3thiazepine and 1,4thiazepine benzothiazepines have a single benzene attached to the ring, while dibenzothiazepines have two. We have been interested in 1, 5 benzothiazepine derivatives and have prepared and evaluated its central nervous actions in experimental animals. As 1, 5 benzothiazepine plays an important role in the pharmacological and medicinal field, various researchers are interested in its synthesis 12 and characteristics, 14. To control tachycardia, diltiazem is also given after antithyroid therapy in such patient where beta blockers are. October december 176 have been found active against different families of targets 1924.
A pharmacophore model of the benzodiazepine binding site on the gaba a receptor. The parent 1, 5 benzothiazepine, 1, itself has not hitherto been described in the literature for its pharmacological properties. Examples of 1, 5 benzothiazepine derivatives with interesting biological properties. Efficieant synthesis of 1, 5 benzothiazepine derivatives. Diltiazem general description diltiazem is less potent calcium channel blockers than verapamil and dihydrpyridines. Process for the preparation of derivatives of 1, 5 benzothiazepin4one of general formula in which each of r, r1, r2 and r3, which are identical or different, denotes a c1c4 alkyl radical and y denotes a c1c4 alkylene radical and their pharmaceutically acceptable salts, comprising the stages of.
Newer applications of 1,5benzothiazepines and their. Jun 16, 2010 moreover, a benzothiazepine from the same set of compounds having a 2thiophene moiety as ring b was found to be the most potent inhibitor of both ache and bche, with ic 50 values of 5. Asian journal of pharmaceutical analysis and medicinal chemistry. Full text pdf 953k abstracts citedby29 reaction of 2aminothiophenols and phenylglicidic esters gave 2hydroxy3 2aminophenylthio 3phenylpropionic esters vi and 2phenyl3hydroxy2, 3dihydro 1, 5 benzothiazepin4 5h ones vii. However, its derivatives belong to the most frequently studied moieties. The structures of these novel compounds were confirmed by spectrum, elemental, and xray crystallographic analysis. Benzothiazepines 5 play a unique role in drug discovery programs. For example, if you send a pdf package to a client using acrobat 6, they will be prompted to download the latest version of the free adobe reader to view it. Prakash department of chemistry, university of rajasthan, jaipur 302 004 india. Synthesis and in vitro study of novel methylenebisphenyl 1, 5 benzothiazepine s and methylenebisbenzofuryl 1, 5 benzothiazepine s as antimicrobial agents. The common strategy for the construction of the 1, 5 benzothiazepine moiety is the reaction of 1,3diarylprop2enones with oaminothiophenol or 1,3difunctional threecarbon building blocks.
Process for preparing 1,5benzothiazepine derivatives. Modulation of constitutive androstane receptor car and. Moreover, a benzothiazepine from the same set of compounds having a 2thiophene moiety as ring b was found to be the most potent inhibitor of both ache and bche, with ic 50 values of 5. The major approaches, for synthesis of 1, 5 benzothiazepinones are cyclization and ring expansion. Synthesis and biological evaluation of 5hindolo 3,2b 1, 5 benzothiazepine derivatives, designed as conformationally constrained analogues of the human immunodeficiency virus type 1 reverse. Molecular docking based screening of g6ps with 1, 5 benzothiazepine derivates for a potential inhibitor maruthi malya prasada rao chennu, 1, rahaman shaik abdul, 2 and rajendra prasad yejella 3 1 department of pharmaceutical chemistry, qis college of pharmacy. Asymmetric reduction of a 1,5benzothiazepine derivative. Molecular docking based screening of g6ps with 1, 5 benzothiazepine derivates for a potential inhibitor maruthi malya prasada rao chennu 1, rahaman shaik abdul2, rajendra prasad yejella3 1department of pharmaceutical chemistry, qis college of pharmacy. Authors would like to thank innovative informatica technologies for providing the necessary training and facilities.
Bioactivity and targets 1, 5 benzothiazepine nucleus is present in a number of clinically used drugs such as diltiazem, clentiazem, thiazesim, quetiapine, and clothiapine. The aim of the present work was to design and synthesize some new 1, 5 benzothiazepine derivatives carrying biologically active thiazepine moieties that were expected to have antibreast cancer activity. Organic chemistry department, alazhar university, nasr city, cairo, 11884, egypt. Synthesis of 2,4substituted 1, 5 substituted benzothiazepine was first carried out by the acetylation of substituted. Synthesis and antimicrobial screening of new chalcones and. The mechanism of the increasing action of ta993, a new 1. Pdf syntheses of some new 1,5benzothiazepine derivatives. They display a wide spectrum of biological activities such as anti anxiety, anti depressant and anticataleptic e. M, respectively named compound a in this study figure 1. Physicochemical and spectroscopical characterization of all the 1, 5 benzothiazepine is confirmed by checking of ir spectra. Synthesis and in vitro antibreast cancer activity of some. Molecular docking based screening of g6ps with 1, 5.
Optically active 1, 5 benzothiazepines belong to the well known benzothiazepine type substances. General procedure for the optimizationremovedof thebysynthesis of 2,3dihydro 1, 5 benzothiazepine 4a to a stirred solution of chalcone 1a 26 mg, 0. The parent 1, 5 benzothiazepine, itself, has not hitherto been described in the literature for its pharmacological properties. International journal of scientific and research publications, volume 4, issue 12, december 2014 1 issn 22503153. Synthesis and evaluation of novel 1, 5 benzothiazepine. Examples of 1,5benzothiazepine derivatives with interesting biological properties. Ly170053, 2methyl44methyl 1 piperazinyl10hthieno2,3b 1, 5 benzodiazepine and st2472 st. A process for preparing 1, 5 benzothiazepine derivatives of the formula.