- Synthesis of substituted phenanthrene-9-benzimidazole conjugates: Cytotoxicity evaluation and apoptosis inducing studies
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A series of new phenanthrene-9-benzimidazole conjugates has been synthesized by condensing phenanthrene aldehydes with various substituted o-phenylenediamines. The title compounds were evaluated for their in vitro cytotoxic potential against various human
- Kumar, Niggula Praveen,Sharma, Pankaj,Kumari, S. Sujana,Brahma, Umarani,Nekkanti, Shalini,Shankaraiah, Nagula,Kamal, Ahmed
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- Novel benzimidazole-triazole hybrids as apoptosis inducing agents in lung cancer: Design, synthesis, 18F-radiolabeling & galectin-1 inhibition studies
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In this study, we have synthesized a new series of benzimidazole-triazole hybrids as galectin-1 (gal-1) mediated apoptosis-inducing agents, and evaluated for their potential anticancer activity against a panel of human cancer cell lines viz. breast cancer
- Sridhar Goud, Nerella,Pooladanda, Venkatesh,Muni Chandra,Lakshmi Soukya,Alvala, Ravi,Kumar, Pardeep,Nagaraj, Chandana,Dawn Bharath, Rose,Qureshi, Insaf A.,Godugu, Chandraiah,Alvala, Mallika
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- Regioselective Nitration of N-Alkyl Anilines using tert-Butyl Nitrite under Mild Condition
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Regioselective ring nitration of N-alkyl anilines is reported using tert-butyl nitrite. The reactions proceed efficiently with a wide range of substrates providing synthetically useful N-nitroso N-alkyl nitroanilines in excellent yields which can be easily converted into N-alkyl phenylenediamines and N-alkyl nitroanilines using Zn-AcOH and HCl/MeOH, respectively.
- Chaudhary, Priyanka,Gupta, Surabhi,Muniyappan, Nalluchamy,Sabiah, Shahulhameed,Kandasamy, Jeyakumar
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p. 104 - 119
(2019/01/08)
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- Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents
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In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo[d]imidazol
- Goud, Nerella Sridhar,Ghouse, S. Mahammad,Vishnu, Jatoth,Komal,Talla, Venu,Alvala, Ravi,Pranay, Jakkula,Kumar, Janish,Qureshi, Insaf A.,Alvala, Mallika
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- Construction of Druglike 2-Amido Benzo[ d]imidazole Analogues via Desulfurative Cyclization of Thiourea Intermediate Resin on Solid-Phase
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A 2-amido benzo[d]imidazole library has been constructed by solid-phase synthesis. The key step of this solid-phase synthesis involves the preparation of polymer-bound 2-amino benzo[d]imidazole resin through desulfurative cyclization of thiourea resin using 2-chloro-1,3-dimethylimidazolinium chloride and N,N-diisopropylethylamine in dichloromethane (DCM), and the resin is then functionalized by acylation at the 2-amine position to afford 2-amidobenzo[d]imidazole resin. In the case of 2-amidobenzo[d]imidazole resin having a p-I or m-NO2, the resin was further functionalized by Suzuki/Sonogashira-coupling (p-I) and reduction to the primary amine (m-NO2) followed by acylation. Finally, the functionalized 2-amido-benzo[d]imidazole resin was cleaved from the polymer support by treatment with a cocktail of trifluoroacetic acid and DCM. As a result, we obtained 2-amidobenzo[d]imidazole analogues in high yield and good purities.
- Ryu, Hyun-Jeong,Yang, Seung-Ju,Lee, Gee-Hyung,Gong, Young-Dae
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supporting information
p. 282 - 291
(2018/05/24)
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- Phenylquinoxalinone CFTR activator as potential prosecretory therapy for constipation
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Constipation is a common condition for which current treatments can have limited efficacy. By high-throughput screening, we recently identified a phenylquinoxalinone activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride chan
- Cil, Onur,Phuan, Puay-Wah,Son, Jung-Ho,Zhu, Jie S.,Ku, Colton K.,Tabib, Niloufar Akhavan,Teuthorn, Andrew P.,Ferrera, Loretta,Zachos, Nicholas C.,Lin, Ruxian,Galietta, Luis J.V.,Donowitz, Mark,Kurth, Mark J.,Verkman, Alan S.
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p. 14 - 4,26
(2017/03/22)
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- "All-water" one-pot diverse synthesis of 1,2-disubstituted benzimidazoles: Hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' by water
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A new "all-water" tandem arylaminoarylation/arylaminoalkylation- reduction-cyclisation route is reported for one-pot diversity oriented synthesis of regiodefined 1,2-disubstituted benzimidazoles. Water plays a crucial and indispensable role through hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' in the formation of N-mono-aryl/aryl alkyl/alkyl/cycloalkyl o-nitroanilines under metal and base-free conditions to replace the transition metal-based C-N bond formation (aryl amination) chemistry and underlines the origin of regiodefined installation of the diverse selection of aryl, aryl alkyl, and alkyl/cycloalkyl groups as substituents on the benzimidazole scaffold to form the 1,2-disubstituted benzimidazoles. The influence of the hydrogen bond effect of water in promoting the arylaminoarylation reaction under base and metal-free conditions has been realized through observation of inferior yields in D2O compared to that obtained in water during the reaction of o-fluoronitrobenzene with aniline separately performed in water and D2O under similar experimental conditions. Water also provides assistance in promoting the subsequent nitro reduction and in the final cyclocondensation steps. The role of water in promoting the cyclocondensation reaction through hydrogen bonds is realized by the differential product yields during the reaction of mono-N-phenyl-o- phenylenediamine with benzaldehyde performed separately in water and D 2O. The better hydrogen bond donor and hydrogen bond acceptor abilities of water compared to those of the organic solvents are the contributing/deciding factors for making the new water-assisted tandem arylaminoarylation/arylaminoalkylation-reduction-cyclisation strategy for the diversified synthesis of the regiodefined 1,2-disubstituted benzimidazoles effective in an aqueous medium, making it represent a true "all-water chemistry."
- Kommi, Damodara N.,Jadhavar, Pradeep S.,Kumar, Dinesh,Chakraborti, Asit K.
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p. 798 - 810
(2013/04/24)
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- Identification of novel benzimidazole derivatives as inhibitors of leukotriene biosynthesis by virtual screening targeting 5-lipoxygenase- activating protein (FLAP)
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Pharmacological suppression of leukotriene biosynthesis by 5-lipoxygenase (5-LO)-activating protein (FLAP) inhibitors is a promising strategy to intervene with inflammatory, allergic and cardiovascular diseases. Virtual screening targeting FLAP based on a combined ligand- and structure-based pharmacophore model led to the identification of 1-(2-chlorobenzyl)-2-(1-(4-isobutylphenyl) ethyl)-1H-benzimidazole (7) as developable candidate. Compound 7 potently suppressed leukotriene formation in intact neutrophils (IC50 = 0.31 μM) but essentially failed to directly inhibit 5-LO suggesting that interaction with FLAP causes inhibition of leukotriene synthesis. For structural optimization, a series of 46 benzimidazole-based derivatives of 7 were synthesized leading to more potent analogues (70-72, 82) with IC50 = 0.12-0.19 μM in intact neutrophils. Together, our results disclose the benzimidazole scaffold bearing an ibuprofen fingerprint as a new chemotype for further development of anti-leukotriene agents.
- Banoglu, Erden,Caliskan, Burcu,Luderer, Susann,Eren, Goekcen,Oezkan, Yagmur,Altenhofen, Wolfram,Weinigel, Christina,Barz, Dagmar,Gerstmeier, Jana,Pergola, Carlo,Werz, Oliver
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supporting information; experimental part
p. 3728 - 3741
(2012/08/28)
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- "All-water" chemistry of tandem N-alkylation-reduction- condensation for synthesis of N-arylmethyl-2-substituted benzimidazoles
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A water-assisted tandem N-alkylation-reduction-condensation process has been devised as a new synthetic route for the one-pot synthesis of N-arylmethyl-2-substituted benzimidazoles. Water plays the crucial and indispensable role through hydrogen bond mediated 'electrophile-nucleophile dual activation' in promoting selective N-monobenzylation of o-nitroanilines as an alternative to the transition metal-based chemistry for C-N bond formation (amination) and forms the basis of disposing the substituents on the benzimidazole moiety in regiodefined manner. Water also exerts a beneficial effect in the condensation of N-monobenzylated o-phenylenediamines with aldehydes. The water-assisted C-N bond formation chemistry led to metal/base-free synthesis of N-monobenzylated o-nitroanilines and N-monobenzylated o-phenylenediamines. The indispensable/advantageous role of water in the various stage of the N-alkylation-reduction-condensation process exemplifies an 'all-water' chemistry for the synthesis of N-arylmethyl-2- substituted benzimidazoles.
- Kommi, Damodara N.,Kumar, Dinesh,Bansal, Rohit,Chebolu, Rajesh,Chakraborti, Asit K.
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p. 3329 - 3335
(2013/01/16)
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- Novel benzo[d]imidazole-2(3H)-thiones as potent inhibitors of the α-melanocyte stimulating hormone induced melanogenesis in melanoma B16 cells
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In order to determine the optimum size of heterocycle of lead compound 1 (6-methyl-3-phenethyl-3,4-dihydro-1H-quinoline-2-thione; IC50=0.8 μM) for inhibition of melanogenesis, we have synthesized and evaluated some benzimdazole-2(3H)-thiones 5a
- Lee, Jee-Hyun,Thanigaimalai, Pillaiyar,Lee, Ki-Cheul,Bang, Seong-Cheol,Kim, Min-Seok,Sharma, Vinay Kumar,Yun, Cheong-Yong,Roh, Eunmiri,Kim, Youngsoo,Jung, Sang-Hun
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experimental part
p. 918 - 921
(2010/09/04)
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- Applicability aspects of transition metal-catalyzed aromatic amination protocols in medicinal chemistry
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The application of palladium- and coppercatalyzed reactions for the aromatic amination of pharmacologically relevant scaffolds is investigated. The focus is set on the scope of several protocols for the introduction of amines of broad structural diversity, allowing for the synthesis of numerous derivatives of one biological hit structure for screening in biological assay systems. Thus, attaining optimized yields and TONs had not a major priority, most important were practical aspects, that is no further purification and drying of reagents and solvents had to be envisaged, ideally only a few transition metalbased protocols had to be applied for synthesizing structurally diverse compounds in sufficient amounts (several milligrams) for screening without any finetuning of conditions and catalytic systems.
- Tasler, Stefan,Mies, Jan,Lang, Martin
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p. 2286 - 2300
(2008/09/19)
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- Specific features of nucleophilic substitution in 1-chloro-3,4- dinitrobenzene
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Effects of the solvent, temperature, and nucleophile nature on the selectivity of nucleophilic substitution in 1-chloro-3,4-dinitrobenzene were studied, and optimal conditions were found for the synthesis and isolation of particular products.
- Zotova,Kushakova,Kuznetsov,Rodin,Garabadzhiu
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p. 1473 - 1476
(2007/10/03)
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- Synthesis of N-Benzylated Anilines from the Reaction of Anilines and Benzyl Chloroformate
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Reactions of benzyl chloroformate with a series of substituted anilines produced N-carbobenzyloxy "CBZ" products along with the unexpected N-benzylated "Bn" compounds. Reaction of aniline, 1a, gave the CBZ, or 2a, and Bn, or 3a, products in 29% and 14% yi
- Pati, Hari,Weisbruch, Paul,Lemon, Adrienne,Lee, Moses
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p. 933 - 940
(2007/10/03)
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- New 2-piperazinylbenzimidazole derivatives as 5-HT3 antagonists. Synthesis and pharmacological evaluation
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A series of 2-piperazinylbenzimidazole derivatives were prepared and evaluated as 5-HT3 receptor antagonists. Their 5-HT3 receptor affinities were evaluated by radioligand binding assays, and their abilities to inhibit the 5-HT-induced Bezold-Jarisch reflex in anesthetized rats were determined. Compound 7e (lerisetron, pK(i) = 9.2) exhibited higher affinity for the 5- HT3 receptor than did tropisetron and granisetron, while compound 7q (pK(i) = 7.5) had very low affinity for this receptor, showing that substitution on the N1 atom of the benzimidazole ring is essential for affinity and activity. The effect of substitution on the aromatic ring of benzimidazole by several substituents in different positions is also discussed. A strong correlation between the 5-HT3 antagonistic activity of the studied compounds and the position of substitution on the aromatic ring was established. Thus, while the 4-methoxy derivative 7m showed weak affinity for the 5-HT3 receptor (pK(i) = 6.7), the 7-methoxy derivative 7n exhibited the highest affinity (pK(i) = 9.4). Compounds 7e and 7n are now under further investigation as drugs for the treatment of nausea and emesis evoked by cancer chemotherapy and radiation.
- Orjales, Aurelio,Mosquera, Ramón,Labeaga, Luis,Rodes, Rosa
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p. 586 - 593
(2007/10/03)
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- A 'one-pot' phase transfer alkylation/hydrolysis of o-nitrotrifluoroacetanilides. A convenient route to N-alkyl o-phenylenediamines
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A variety of o-nitrotrifluoroacetanilides undergo a one-pot alkylation/hydrolysis to give N-alkyl o-nitroanilines in 40-94% yield. Dimethylsulfate, benzyl bromide and 1-bromo-propane were used as the electrophiles.
- Brown, Samuel A.,Rizzo, Carmelo J.
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p. 4065 - 4080
(2007/10/03)
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- Synthesis of 1-Alkoxy-2-Alkyl-Benzimidazoles from 2-Nitroanilines via Tandem N-Alkylation-Cyclization-O-Alkylation
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Substituted 2-nitroanilines react with benzylic, allyl and alkyl halides to give 2-aryl-1-benzyloxy-, 1-allyloxy-2-vinyl- and 1-alkoxy-2-alkyl-benzimidazoles, in a one-pot cascade process involving 1-alkylation-cyclization-O-alkylation. 2-Aryl-1-benzyloxy- and 1-allyloxy-2-vinyl- derivatives are obtained in high yields (79-98percent), while with simple alkyl halides, yields of the benzimidazoles are substrate dependent.An X-ray crystal structure of 2,4-dimethyl-1-ethoxybenzimidazole is presented.
- Gardiner, John M.,Loyns, Colin R.,Schwalbe, Carl H.,Barrett, Garry C.,Lowe, Philip R.
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p. 4101 - 4110
(2007/10/02)
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