- Synthetic method for vilazodone intermediate ethyl 5-(1-piperazinyl)-2-benzofuran-2-carboxylate
-
The invention relates to a synthetic method for a vilazodone intermediate, i.e., ethyl 5-(1-piperazinyl)-2-benzofuran-2-carboxylate. The key vilazodone intermediate ethyl 5-(1-piperazinyl)-2-benzofuran-2-carboxylate as shown in a formula I is prepared with 6-nitrocoumarin as a starting raw material through addition, ring opening, intramolecular ring closure, nitro reduction, piperazine ring preparation, etc. The synthetic method is simple in synthetic route, high in the yield of target products and suitable for industrial scale-up production.
- -
-
Paragraph 0035-0037
(2018/03/01)
-
- [...] intermediate synthetic method (by machine translation)
-
The invention relates to a [...] intermediate synthesis method, in order to 6 - nitro coumarin as the starting the raw materials, through ring-opening, the ring in the molecule, esterification, reduction, paipai qin link other steps, to obtain key [...] middle style I compound 5 - (1 - piperazinyl) - 2 - benzofuran - 2 - carboxylic acid ethyl ester. The invention synthetic route is simple, the target product yield is relatively high, and is suitable for industrial scale production. (by machine translation)
- -
-
Paragraph 0041; 0042; 0043
(2018/04/01)
-
- Metal-free deoxygenation and reductive disilylation of nitroarenes by organosilicon reducing reagents
-
A metal-free deoxygenation and reductive disilylation of nitroarenes was achieved using N,N’-bis(trime-thylsilyl)-4,4’-bipyridinylidene (1) under mild and neutral reaction conditions, and a broad functional group tolerance was possible in this reaction. Mono-deoxygenation, giving a synthetically valuable N,O-bis(trimethylsilyl)phe-nylhydroxylamine (7a) as a readily available and safe phenylnitrene source from nitrobenzene, and double-deoxy-genation, giving N,N-bis(trimethylsilyl)anilines 8, were easily controlled by varying the amounts of 1 and reaction temperature as well as adding dibenzothiophene (DBTP). Reaction of 2-arylnitrobenzenes with 1 resulted in the formation of the corresponding carbazoles 14 via in situ-gen-erated phenylnitrene species derived by thermolysis of N,O-bis(trimethylsilyl)phenylhydroxylamines 7, followed by their subsequent intramolecular C H insertion. In addition, the intramolecular N N coupling reaction proceeded in the reduction of 2,2’-dinitrobiphenyl derivatives by 1, giving the corresponding benzo[c]cinnolines.
- Bhattacharjee, Argha,Hosoya, Hiromu,Ikeda, Hideaki,Nishi, Kohei,Tsurugi, Hayato,Mashima, Kazushi
-
supporting information
p. 11278 - 11282
(2018/10/20)
-
- PROCESS FOR THE PREPARATION OF VILAZODONE HYDROCHLORIDE AND ITS AMORPHOUS FORM
-
The present invention relates to an improved process for the preparation of vilazodone Hydrochloride and a process for preparation of novel pure amorphous form of vilazodone hydrochloride.
- -
-
Paragraph 0125
(2015/03/31)
-
- Mild and selective hydrogenation of nitro compounds using palladium nanoparticles supported on amino-functionalized mesocellular foam
-
We present the utilization of a heterogeneous catalyst comprised of Pd nanoparticles supported on aminopropyl-functionalized siliceous mesocellular foam (Pd0-AmP-MCF) for the selective hydrogenation of aromatic, aliphatic, and heterocyclic nitro compounds to the corresponding amines. In general, the catalytic protocol exclusively affords the desired amine products in excellent yields within short reaction times with the reactions performed at room temperature under ambient pressure of H2. Moreover, the reported Pd nanocatalyst displayed excellent structural integrity for this transformation as it could be recycled multiple times without any observable loss of activity or leaching of metal. In addition, the Pd nanocatalyst could be easily integrated into a continuous-flow device and used for the hydrogenation of 4-nitroanisole on a 2.5 g scale, where the product p-anisidine was obtained in 95% yield within 2 h with a Pd content of less than 1 ppm.
- Verho, Oscar,Gustafson, Karl P. J.,Nagendiran, Anuja,Tai, Cheuk-Wai,B?ckvall, Jan-E.
-
p. 3153 - 3159
(2015/02/03)
-
- PROCESS FOR THE PREPARATION OF VILAZODONE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
-
The present invention provides a novel intermediate of vilazodone and its process of preparation. The present invention further provides a process for preparing vilazodone or a pharmaceutically acceptable salt thereof using the novel intermediate.
- -
-
Page/Page column 14
(2014/05/07)
-
- An efficient synthesis and biological screening of benzofuran and benzo[d]isothiazole derivatives for Mycobacterium tuberculosis DNA GyrB inhibition
-
A series of twenty eight molecules of ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate and 3-(piperazin-1-yl)benzo[d]isothiazole were designed by molecular hybridization of thiazole aminopiperidine core and carbamide side chain in eight steps and were screened for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antitubercular activity, cytotoxicity and protein-inhibitor interaction assay through differential scanning fluorimetry. Also the orientation and the ligand-protein interactions of the top hit molecules with MS DNA gyrase B subunit active site were investigated applying extra precision mode (XP) of Glide. Among the compounds studied, 4-(benzo[d]isothiazol-3-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide (26) was found to be the most promising inhibitor with an MS GyrB IC50 of 1.77 ± 0.23 μM, 0.42 ± 0.23 against MTB DNA gyrase, MTB MIC of 3.64 μM, and was not cytotoxic in eukaryotic cells at 100 μM. Moreover the interaction of protein-ligand complex was stable and showed a positive shift of 3.5 °C in differential scanning fluorimetric evaluations.
- Reddy, Kummetha Indrasena,Srihari, Konduri,Renuka, Janupally,Sree, Komanduri Shruthi,Chuppala, Aruna,Jeankumar, Variam Ullas,Sridevi, Jonnalagadda Padma,Babu, Kondra Sudhakar,Yogeeswari, Perumal,Sriram, Dharmarajan
-
p. 6552 - 6563
(2015/02/18)
-
- Design, synthesis, biological evaluation of substituted benzofurans as DNA gyraseB inhibitors of Mycobacterium tuberculosis
-
DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase and is a well-established and validated target for the development of novel therapeutics. By adapting the medium throughput screening approach, we present the discovery and optimization of ethyl 5-(piperazin-1-yl) benzofuran-2- carboxylate series of mycobacterial DNA gyraseB inhibitors, selected from Birla Institute of Technology and Science (BITS) database chemical library of about 3000 molecules. These compounds were tested for their biological activity; the compound 22 emerged as the most active potent lead with an IC50 of 3.2 ± 0.15 μM against Mycobacterium smegmatis DNA gyraseB enzyme and 0.81 ± 0.24 μM in MTB supercoiling activity. Subsequently, the binding of the most active compound to the DNA gyraseB enzyme and its thermal stability was further characterized using differential scanning fluorimetry method.
- Renuka, Janupally,Reddy, Kummetha Indrasena,Srihari, Konduri,Jeankumar, Variam Ullas,Shravan, Morla,Sridevi, Jonnalagadda Padma,Yogeeswari, Perumal,Babu, Kondra Sudhakar,Sriram, Dharmarajan
-
p. 4924 - 4934
(2014/10/16)
-
- PROCESS FOR THE PREPARATION OF VILAZODONE HYDROCHLORIDE AND ITS AMORPHOUS FORM
-
The present invention relates to an improved process for the preparation of vilazodone Hydrochloride and a process for preparation of novel pure amorphous form of vilazodone hydrochloride.
- -
-
Page/Page column 23
(2013/11/05)
-
- Evaluation of radiolabeled (Hetero)aromatic analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for imaging and targeted radionuclide therapy of melanoma
-
Targeted radionuclide therapy using radioiodinated compounds with a specific affinity for melanoma tissue is a promising treatment for disseminated melanoma, but the candidate with the ideal kinetic profile remains to be discovered. Targeted radionuclide therapy concentrates the effects on tumor cells, thereby increasing the efficacy and decreasing the morbidity of radiotherapy. In this context, analogues of N-(2-diethylaminoethyl)-4- iodobenzamide (BZA) are of interest. Various (hetero)aromatic analogues 5 of BZA were synthesized and radioiodinated with 125I, and their biodistribution in melanoma-bearing mice was studied after i.v. administration. Most [125I]5-labeled compounds appeared to bind specifically and with moderate-to-high affinity to melanoma tumor. Two compounds, 5h and 5k, stood out with high specific and long-lasting uptake in the tumor, with a 7- and 16-fold higher value than BZA at 72 h, respectively, and kinetic profiles that makes them promising agents for internal targeted radionuclide therapy of melanoma.
- Chezal, Jean-Michel,Papon, Janine,Labarre, Pierre,Lartigue, Claire,Galmier, Marie-Josephe,Decombat, Caroline,Chavignon, Olivier,Maublant, Jean,Teulade, Jean-Claude,Madelmont, Jean-Claude,Moins, Nicole
-
experimental part
p. 3133 - 3144
(2009/04/07)
-
- GPCR AGONISTS
-
Compounds of formula (I): or pharmaceutically acceptable salts thereof, are GPCR agonists and are useful as for the treatment of obesity and diabetes.
- -
-
Page/Page column 25
(2008/06/13)
-
- BUILDING BLOCKS FOR DNA BINDING AGENTS
-
The invention provides an alkylator that is an analog of a compound based on 5-oxo-1a,2,3,5-tetrahydro-1H-3-aza-cyclopropa[c]indene-7-carboxylic acid, 9a-chloromethyl-4-oxo-2,4,9,9a-tetrahydro-1H-2-aza-cyclopropa[1,5]cyclopenta[1,2-a]naphthalene-7-carboxylic acid, or 4-oxo-1,2,4,5,8,8a-hexahydrocyclopropa[c]pyrrolo[3,2-e]indole-6-carboxylic acid and conjugates thereof.
- -
-
Page/Page column 5; 29
(2008/06/13)
-
- EP2 RECEPTOR AGONISTS
-
A compound of Formula (I) or a salt, solvate and chemically protected form thereof, wherein: R5 is an optionally substituted C5-20 aryl or C4-20 alkyl group; A is selected from the group consisting of Formulae (Ai), (Aii), (Aiii) D is selected from Formulae (Di), (Dii), (Diii), (Div), (Dv) B is selected from the group consisting of Formulae (Bi), (Bii), (Biii), (Biv) (Bv).
- -
-
Page/Page column 145
(2008/06/13)
-
- Synthesis and structure-activity relationship in a class of indolebutylpiperazines as dual 5-HT1A receptor agonists and serotonin reuptake inhibitors
-
Systematic structural modifications of indolealkylphenylpiperazines led to improved selectivity and affinity within this class of 5-HT1A receptor agonists. Introduction of electron-withdrawing groups in position 5 on the indole raises serotonin transporter affinity, and the cyano group proved to be the best substituent here. 5-Fluoro and 5-cyano substituted indoles show comparable results in in vitro and in vivo tests, and bioisosterism between these substituents was supported by calculation of the molecular electrostatic potentials and dipole moments. Compounds showing promising in vitro data were further examined in ex vivo (p-chloroamphetamine assay) and in vivo (ultrasonic vocalization) tests. Optimization of the arylpiperazine moiety indicated that the 5-benzofuranyl-2-carboxamide was best suited to increase 5-HT transporter and 5-HT1A receptor affinity and to suppress D2 receptor binding. 5-{4-[4-(5-Cyano-3-indolyl)butyl]-1-piperazinyl}benzofuran-2- carboxamide 29 (vilazodone, EMD 68843) was identified as a highly selective 5-HT1A receptor agonist [GTPγS, ED50 = 1.1 nM] with subnanomolar 5-HT1A affinity [IC50 = 0.2 nM] and as a subnanomolar 5-HT reuptake inhibitor [RUI = 0.5 nM] showing a great selectivity to other GPCRs (e.g., D2, IC50 = 666 nM).
- Heinrich, Timo,B?ttcher, Henning,Gericke, Rolf,Bartoszyk, Gerd D.,Anzali, Soheila,Seyfried, Christoph A.,Greiner, Hartmut E.,Van Amsterdam, Christoph
-
p. 4684 - 4692
(2007/10/03)
-
- Synthesis and antitumor activity of new benzoheterocyclic derivatives of distamycin A
-
The design, synthesis, and in vivo and in vitro antileukemic activity of a novel series of compounds (13-22 and 34), in which different benzoheterocyclic rings, bearing a nitrogen mustard or a benzoyl nitrogen mustard or an α-bromoacryloyl group as alkylating moieties, are tethered to a distamycin frame, are reported, and structure-activity relationships are discussed. The new derivatives were prepared by coupling nitrogen mustard- substituted, benzoyl nitrogen mustard-substituted, or α- bromoacryloyl-substituted benzoheterocyclic carboxylic acids 23- 32 with desformyldistamycin (33) or in one case with its two- pyrrole analogue 35. With very few exceptions, the activities of compounds bearing the same alkylating moiety are slightly affected by the kind of the heteroatom present on the benzoheterocyclic ring. All novel compounds, with one exception, showed in vitro activity against L1210 murine leukemia cell line comparable to or better than that of tallimustine. The compounds in which the nitrogen mustard and the α-bromoacryloyl moieties are directly linked to benzoheterocyclic ring showed potent cytotoxic activities (IC50 ranging from 2 to 14 nM), while benzoyl nitrogen mustard derivatives of benzoheterocycles showed reduced cytotoxic activities, and one compound (16) of this cluster was the sole derivative devoid of significant activity. Compound 18, a 5-nitrogen mustard N-methylindole derivative of distamycin, showed the best antileukemic activity in vivo, with a very long survival time (%T/C = 457), significantly increased in comparison to tallimustine (%T/C = 133), and was selected for further extensive evaluation. Arrested polymerase chain reaction and direct DNA fragmentation assays were performed for compound 18 and the structurally related compounds 13-17 and 19. The results obtained have shown that both alkylating groups and oligopeptide frames play a crucial role in the sequence selectivity of these compounds.
- Baraldi, Pier Giovanni,Romagnoli, Romeo,Beria, Italo,Cozzi, Paolo,Geroni, Cristina,Mongelli, Nicola,Bianchi, Nicoletta,Mischiati, Carlo,Gambari, Roberto
-
p. 2675 - 2684
(2007/10/03)
-