- Efficient total synthesis of lissodendrin b, 2-aminoimidazole marine alkaloids isolated from lissodendoryx (acanthodoryx) fibrosa
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Lissodendrin B is a 2-aminoimidazole alkaloid bearing a (p-hydroxyphenyl) glyoxal moiety that was isolated from the Indonesian sponge Lissodendoryx (Acanthodoryx) fibrosa. We reported the first efficient total synthesis of Lissodendrin B. The precursor 4,5-disubstituted imidazole was obtained through Suzuki coupling and Sonogashira coupling reactions from 4-iodoimidazole. C2-azidation and reduction of the azide then provided the core structures of Lissodendrin B. Subsequent triple-bond oxidation, demethylation, and deacetylation gave the final product. The synthesis approach consists of ten steps with an overall yield of 1.1% under mild reaction conditions, and it can be applied for future analog synthesis and biological studies.
- Wei, Xianfeng,Hu, Xuelong,Yu, Rilei,Wan, Shengbiao,Jiang, Tao
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Read Online
- Novel synthesis of N-unsubstituted imidazoles via the cycloaddition of N-(tert-butylsulfinyl)imines and TosMIC
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A facile and efficient method was developed for the synthesis of N-unsubstituted imidazoles via the cycloaddition of N-sulfinyl imines and p-toluenesulfonylmethyl isocyanide (TosMIC). This methodology is operationally simple and useful for the preparation of various aromatic and heteroaromatic imidazoles in good to excellent yields.
- Babu Shubha, Priya,Prasad, Hari,Ramaiah, Manjunatha M.,Shivananju, Nanjunda Swamy
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supporting information
(2020/02/15)
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- Preparation of Imidazole Derivatives via Bisfunctionalization of Alkynes Catalyzed by Ruthenium Carbonyl
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A one-step, oxidative bisfunctionalization of alkynes to generate cis -enediol diacetates catalyzed by ruthenium carbonyl (triruthenium dodecacarbonyl) is presented. The reaction was performed using the alkyne, (diacetoxyiodo)benzene, Ru 3 (CO) 12 as the catalyst, and toluene as the solvent at 100 °C to give the cis -enediol diacetates in up to 82percent yields. This method overcomes the shortcomings of existing methods, such as tedious reaction steps, substrate limitations, and the use of toxic reagents. Furthermore, the reaction of module cis -enediol diacetates with ammonium carbonate [(NH 4) 2 CO 3 ] in an alcohol solvent gave imidazole derivatives in 37-84percent yields, thus providing a simple and mild new method for the synthesis of imidazole compounds.
- Chen, Yue-Peng,Gu, Ling-Hui,He, Ling,Luo, Yang,Ruan, Yi-Tong,Yang, Ze
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supporting information
p. 3520 - 3528
(2019/09/07)
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- Identification and Profiling of Hydantoins - A Novel Class of Potent Antimycobacterial DprE1 Inhibitors
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Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-β-d-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.
- Rogacki, Maciej K.,Pitta, Eleni,Balabon, Olga,Huss, Sophie,Lopez-Roman, Eva Maria,Argyrou, Argyrides,Blanco-Ruano, Delia,Cacho, Monica,Vande Velde, Christophe M. L.,Augustyns, Koen,Ballell, Lluis,Barros, David,Bates, Robert H.,Cunningham, Fraser,Van Der Veken, Pieter
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supporting information
p. 11221 - 11249
(2019/01/08)
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- Synthesis and biological activity of 5-(4-methoxyphenyl)-oxazole derivatives
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5-(4′-Methoxyphenyl)-oxazole (MPO), originally reported as a synthetic compound, was isolated from fungal culture broth as an inhibitor of hatch and growth of Caenorhabditis elegans. Nineteen MPO derivatives were chemically synthesized, but showed no effect on C. elegans hatch and growth. These findings strongly suggested that the whole structure of MPO is essential for anti-C. elegans activity.
- Yamamuro, Daisuke,Uchida, Ryuji,Ohtawa, Masaki,Arima, Shiho,Futamura, Yushi,Katane, Masumi,Homma, Hiroshi,Nagamitsu, Tohru,Osada, Hiroyuki,Tomoda, Hiroshi
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supporting information
p. 313 - 316
(2015/04/13)
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- Imidazole analogues of resveratrol: Synthesis and cancer cell growth evaluation
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Novel trans-restricted analogues of resveratrol in which the C-C double bond of the natural derivative has been replaced by diaryl substituted imidazole analogues have been designed. The syntheses of 1,4-, 2,4-, and 2,5-diarylimidazoles, in which the two
- Bellina, Fabio,Guazzelli, Nicola,Lessi, Marco,Manzini, Chiara
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p. 2298 - 2305
(2015/03/30)
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- UREA COMPOUNDS AND THEIR USE AS FAAH ENZYME INHIBITORS
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There is provided a compound having Formula I:(I) wherein: R1 is aryl which is optionally substituted with one or more groups selected from hydroxyl, halogen and C1-4 alkoxy, or R1 is aryl which is substituted with a second aryl group or an aryloxy group, wherein the second aryl group or the aryloxy group is optionally substituted with one or more groups selected from hydroxyl, halogen and C1-4 alkoxy; R2 is C1-4 alkyl; R3 is selected from hydroxyl and OSO2CH3; R4 and R5 are independently selected from hydrogen, hydroxyl and halogen; and n is 0 or 1; or a pharmaceutically acceptable salt thereof; wherein when R3 is hydroxyl and R4 and R5 are not hydroxyl, the optionally substituted aryl group, second aryl group or aryloxy group of R1 is substituted with one or more hydroxyl groups or C1-4 alkoxy groups, or wherein when R3 is hydroxyl, one of R4 and R5 is hydroxyl, provided that the compound is not N-(1-benzylpiperidin-4-yl)-4-(3,4-dihydroxyphenyl)-N-methyl-1H-imidazole-1-carboxamide hydrobromide. The compound may be used as an inhibitor of fatty acid amide hydrolase.
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Page/Page column 30
(2015/02/25)
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- UREA COMPOUNDS AND THEIR USE AS FAAH ENZYME INHIBITORS
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A compound having Formula (I): wherein: R1 is selected from hydrogen, halogen, hydroxyl and C1-4 alkoxy; R2 is selected from hydrogen, halogen, hydroxyl and C1-4 alkoxy; R3 is C1-4 alkyl; R4 is aryl which is substituted with a group selected from OSO2NH2, NHCONH2, NHSO2NH2, NHSO2C1-4 alkyl and CONH2; and n is 0 or 1; or a pharmaceutically acceptable salt thereof; provided that the compound is not N-(1-benzylpiperidin-4-yl)-N-methyl-4-(4-(sulfamoylamino)phenyl)-1H-imidazole-1-carboxamide or N-(1-benzylpiperidin-4-yl)-N-methyl-4-(3-(methylsulfonamido)phenyl)-1H-imidazole-1-carboxamide. The compound may be used as an inhibitor of fatty acid amide hydrolase.
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Page/Page column 24
(2015/02/25)
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- One-pot synthesis of 2-alkyl-4(5)-aryl-1H-imidazoles from 1-aryl-2-bromoethanones, ammonium carbonate and aliphatic carboxylic acids
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A simple and efficient protocol for the preparation of 2-alkyl-4(5)-aryl- 1H-imidazoles starting from α-bromo aryl methyl ketones and aliphatic carboxylic acids in the presence of ammonium carbonate has been developed.
- Liu, Cong,Nie, Yijiao,Yao, Guowei,Dai, Rongji,Deng, Yulin
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p. 208 - 210
(2014/05/06)
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- PIPERAZINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLU5 RECEPTORS
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This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurologic
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Page/Page column 32
(2013/07/05)
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- NOVEL COMPOUNDS
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This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurologic
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Paragraph 0145; 0146
(2013/06/28)
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- Highly selective synthesis of 4(5)-aryl-, 2,4(5)-diaryl-, and 4,5-diaryl-1H-imidazoles via Pd-catalyzed direct C-5 arylation of 1-benzyl-1H-imidazole
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Highly selective, practical, and efficient protocols for the preparation of 4(5)-aryl-1H-imidazoles 2, 2,4(5)-diaryl-1H-imidazoles 3, and 4,5-diaryl-1H-imidazoles 1 are described. A key step of these protocols is the regioselective synthesis of 5-aryl-1-benzyl-1H-imidazoles 9 by Pd-catalyzed direct C-5 arylation of commercially available 1-benzyl-1H-imidazole (8) with aryl halides. The three-step synthesis of compounds 3 from 8 also involves the Pd-catalyzed and Cu-mediated direct C-2 arylation of imidazoles 9 with aryl halides under base-free and ligandless conditions. On the other hand, the four-step synthesis of imidazoles 1 from 8 also involves the regioselective bromination of compounds 9 and a Suzuki reaction of the resulting 5-aryl-1-benzyl-4-bromo-1H-imidazoles 11 with arylboronic acids 5 under phase-transfer conditions, followed by N-debenzylation.
- Bellina, Fabio,Cauteruccio, Silvia,Di Fiore, Annarita,Marchetti, Chiara,Rossi, Renzo
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p. 6060 - 6072
(2008/12/20)
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- A new boronic-acid based strategy to synthesize 4(5)-(het)aryl-1H-imidazoles
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This paper describes the synthesis of a new N-THP protected 5-(1H)-imidazolyl boronic acid pinacol ester and its use in Suzuki cross-coupling reactions with a wide range of (het)aryl halides to provide 4(5)-(het)aryl-1H-imidazoles.
- Primas, Nicolas,Mahatsekake, Clément,Bouillon, Alexandre,Lancelot, Jean-Charles,Oliveira Santos, Jana Sopkovà-de,Lohier, Jean-Fran?ois,Rault, Sylvain
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p. 4596 - 4601
(2008/09/20)
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- Efficient and practical synthesis of 4(5)-aryl-1H-imidazoles and 2,4(5)-diaryl-1H-imidazoles via highly selective palladium-catalyzed arylation reactions
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(Chemical Equation Presented) 4(5)-Aryl-1H-imidazoles can be efficiently and selectively prepared by PdCl2(dppf)-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-1H-imidazole with arylboronic acids under phase-transfer conditions. On the other hand, N-unprotected 4(5)-aryl-1H-imidazoles can undergo highly selective Pd(OAc)2- catalyzed and CuI-mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-1H-imidazoles in modest to good yields. No N-arylation byproducts are observed under the experimental conditions used to prepare 2,4(5)-diaryl-1H-imidazoles.
- Bellina, Fabio,Cauteruccio, Silvia,Rossi, Renzo
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p. 8543 - 8546
(2008/03/11)
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- NOVEL HETEROARYL DERIVATIVE
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A heteroaryl derivative of the formula (1): (wherein Ring Z is an optionally substituted heteroaryl, R1 is a carboxyl group or an alkoxycarbonyl group, etc., W1 and W2 are an optionally substituted lower alkylene, Ar1 is an optionally substituted arylene or an optionally substituted heteroarylene, W3 is a single bond, a lower alkylene, a lower alkenylene, etc., W4 is a single bond, -NR10-, etc., Ar2 is an optionally substituted aryl or an optionally substituted heteroaryl), or a prodrug thereof, or a pharmaceutically acceptable salt thereof.
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Page/Page column 35
(2008/06/13)
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- Imidazolylpyrimidine based CXCR2 chemokine receptor antagonists
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An imidazolylpyrimidine was identified in a CXCR2 chemokine receptor antagonist screen and was optimized for potency, in vitro metabolic stability, and oral bioavailability. It was found that subtle structural modification within the series affected the o
- Ho, Koc-Kan,Auld, Douglas S.,Bohnstedt, Adolph C.,Conti, Paolo,Dokter, Wim,Erickson, Shawn,Feng, Daming,Inglese, Jim,Kingsbury, Celia,Kultgen, Steven G.,Liu, Rong-Qiang,Masterson, Christopher M.,Ohlmeyer, Michael,Rong, Yajing,Rooseboom, Martijn,Roughton, Andrew,Samama, Philippe,Smit, Martin-Jan,Son, Ellen,van der Louw, Jaap,Vogel, Gerard,Webb, Maria,Wijkmans, Jac,You, Ming
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p. 2724 - 2728
(2007/10/03)
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- 1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI)
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1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI.
- Heerding, Dirk A.,Chan, George,DeWolf Jr., Walter E.,Fosberry, Andrew P.,Janson, Cheryl A.,Jaworski, Deborah D.,McManus, Edward,Miller, William H.,Moore, Terrance D.,Payne, David J.,Qiu, Xiayang,Rittenhouse, Stephen F.,Slater-Radosti, Courtney,Smith, Ward,Takata, Dennis T.,Vaidya, Kalindi S.,Yuan, Catherine C.K.,Huffman, William F.
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p. 2061 - 2065
(2007/10/03)
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- Synthesis of polycarpine, a cytotoxic sulfur-containing alkaloid from the ascidian Polycarpa Aurata, and related compounds
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Polycarpine 1, a highly cytotoxic marine natural product, has been synthesized in three steps from p-methoxyphenacyl bromide 4 in 57% overall yield. The key reaction for construction of the symmetrically substituted disulfide linkage of polycarpine is the treatment of 2-amino-4-(4-methoxyphenyl)-1-methylimidazole 17 with S2Cl2 in acetic acid. In a similar way ten related compounds, including three thiazole analogues, have been prepared. Most of them exhibit high cytotoxic activities against an array of human cancer cell lines.
- Radchenko, Oleg S.,Novikov, Vyacheslav L.,Willis, Richard H.,Murphy, Peter T.,Elyakov, George B.
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p. 3581 - 3584
(2007/10/03)
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- A Two-Step Synthesis of Imidazoles from Aldehydes via 4-Tosyloxazolines
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Imidazoles with substituents in the 4- and 4,5-positions were prepared by heating 4-tosyloxazolines in saturated methanolic ammonia.Similar treatment of these oxazolines with monoalkylamines regioselectively affords 1,4-disubstituted imidazoles.When oxazolines bearing an ethyl group at the 4-position were heated with alkylamines, however, a regioisomeric mixture of di- or trisubstituted imidazoles was produced.These reactions proceed via an intermolecular condensation of α-amino ketones and amidines or intramolecular cyclization of α-amidino ketone intermediates, respectively.
- Horne, David A.,Yakushijin, Kenichi,Buechi, George
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p. 139 - 154
(2007/10/02)
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- CARBENIC REACTIONS OF 4-DIAZO-4H-IMIDAZOLE WITH BENZENE DERIVATIVES
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The electrophilic behavior of 4H-imidazolylidene is greatly modified by coordinating groups in benzene derivatives undergoing substitution.
- Amick, T. J.,Shechter, H.
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p. 901 - 904
(2007/10/02)
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