- Design of benzimidazole- and benzoxazole-2-thione derivatives as inhibitors of bacterial hyaluronan lyase
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Bacterial hyaluronan lyases (Hyal) degrade hyaluronan, an important component of the extracellular matrix, and are involved in microbial spread. Hyal inhibitors may serve as tools to study the role of the enzyme, its substrates and products in the course of bacterial infections. Moreover, such enzyme inhibitors are potential candidates for antibacterial combination therapy. Based on crystal structures of Streptococcus pneumoniae Hyal in complex with a hexasaccharide substrate and with different inhibitors, 1-acylated benzimidazole-2-thiones and benzoxazole-2-thiones were derived as new leads for the inhibition of Streptococcus agalactiae strain 4755 Hyal. Structure-based optimization led to N-(3-phenylpropionyl)benzoxazole-2-thione, one of the most potent compounds known to date (IC50 values: 24 μM at pH 7.4, 15 μM at pH 5). Among the 27 new derivatives, other N-acylated benzimidazoles and benzoxazoles are just as active at pH 7.4, but not at pH 5. The results support a binding mode characterized by interactions with residues in the catalytic site and with a hydrophobic patch.
- Braun, Stephan,Botzki, Alexander,Salmen, Sunnhild,Textor, Christian,Bernhardt, Günther,Dove, Stefan,Buschauer, Armin
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experimental part
p. 4419 - 4429
(2011/11/06)
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- Design and synthesis of 3-acyl-2(3H)-benzoxazolone and 3-acyl-2(3H)- benzothiazolone derivatives
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A simpler and efficient "green" method using solid sodium hydroxide in a solvent mixture of acetone/water was found to catalyze N-acylation of 2(3H)-benzoxazolones and 2(3H)-benzothiazolones for facile and rapid synthesis of N-acyl derivatives in excellent yields. This method was applied to the synthesis of a series of 132 compounds employing a variety of acyl chlorides. Graphical abstract: [Figure not available: see fulltext.]
- Guenadil, Faouzi,Aichaoui, Hocine,Kapanda, Coco N.,Lambert, Didier M.,McCurdy, Christopher R.,Poupaert, Jacques H.
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experimental part
p. 67 - 80
(2011/09/20)
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- Synthesis of benz[d]oxazolones involving concomitant acetyl migration from oxygen to nitrogen
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Heating of o-acetoxybenzoyl azides 6-10 in toluene leads to the Curtius reaction, which, when followed by closure of oxazolone ring with concomitant migration of acetyl group from oxygen to nitrogen, produces 3-acetoxybenz[d] oxazol-2(3H)-ones 11-15, which undergo hydrolysis with hot dilute hydrochloric acid to furnish benz[d]oxazol-2(3H)-ones 17-21. Thermal reaction of 2-hydroxy-5-nitrobenzoyl azide (22) in toluene finally yields a mixture of 5-nitrobenz[d]oxazol-2(3H)-one (20) and 5-nitrobenz[d]isoxazol-3(2H)-one (23). Copyright Taylor & Francis Group, LLC.
- Ray, Sibdas,Ghosh, Sukla
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experimental part
p. 2377 - 2388
(2010/09/07)
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- Electrogenerated N-heterocyclic carbenes: N-functionalization of benzoxazolones
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A simple electrochemical procedure for the N-acylation and N-alkylation of benzoxazol-2(3H)-ones has been set up via electrolysis of an ionic liquid containing a benzoxazolone followed by addition of saturated or unsaturated anhydrides or alkyl halides. The electrochemically induced N-functionalization of benzoxazol-2(3H)-ones works very well in all tested ionic liquids, avoiding the use of volatile organic solvents. The N-acyl and N-alkyl derivatives of benzoxazol-2(3H)-ones were isolated in good to excellent yields; moreover, the ionic liquid has been reused fivefold maintaining the high yield of the products.
- Chiarotto,Feroci,Orsini,Sotgiu,Inesi
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experimental part
p. 3704 - 3710
(2009/09/05)
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- Efficient and selective deprotection method for N-protected 2(3H)-benzoxazolones and 2(3H)-benzothiazolones
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Cyclic carbamate flanked with heterocyclic or aliphatic moieties are frequently used in medicinal chemistry. The synthesis of derivatives bearing a free NH often requires the use of a protection method. A literature search reveals very few protection/deprotection methods for cyclic carbamates. In this paper, we described different methods applicable to 2(3H)-benzoxazolone and 2(3H)-benzothiazolone. Graphical abstract
- Carato, Pascal,Yous, Sa?d,Sellier, Didier,Poupaert, Jacques H.,Lebegue, Nicolas,Berthelot, Pascal
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p. 10321 - 10324
(2007/10/03)
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- Sixteen-membered macrolide compounds
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The present invention provides novel sixteen-membered macrolide compounds that are useful as anti-infective agents or as intermediates thereto. The present invention also provides methods for the preparation of these compounds, and methods and formulations for their use. In one aspect of the present invention, sixteen-membered macrolide possessing a side chain Z are provided where Z is aliphatic, aryl, alkylaryl, halide, ═NOR3, ═NNHR3, or —W—R3 where W is O, S, NC(═O)R4, NC(═O)OR4, NC(═O)NHR4 or NR4 where R3 and R4 are each independently hydrogen, aliphatic, aryl or alkylaryl. In another aspect of the present invention, bicyclic compounds are provided where one of the cyclic-components is a sixteen-membered macrolide and the other is a cyclic moiety whose cyclic structure is formed by between 3 and 10 atoms. In another aspect of the present invention, sixteen-membered macrolide compounds that bind to the domain II region of the 23S RNA are provided.
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- 'Fries like' rearrangement: A novel and efficient method for the synthesis of 6-acyl-2(3H)-benzoxazolones and 6-acyl-2(3H)-benzothiazolones
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6-Acyl-2(3H)-benzoxazolone and 6-acyl-2(3H)-benzothiazolone derivatives have particularly interesting anti-inflammatory, antiepileptic, analgesic and antiviral properties. In this study, we report an original method of acylation on the 6-position of 2(3H)-banzoxazolone and 2(3H)benzothiazolone which consists in a two-step procedure involving migration of the acyl group from the N-position to the 6-position of the hetexocycle, at 165 °C and catalyzed by AlCl3. This new procedure was found to be more efficient with regard to the consumption of AICI3 and the yield (76-90%) than other acylation methods previously described.
- Ucar, Huseyin,Van Derpoorten, Kim,Depovere, Paul,Lesieur, Daniel,Isa, Majed,Masereel, Bernard,Delarge, Jacques,Poupaert, Jacques H.
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p. 1763 - 1772
(2007/10/03)
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- Synthesis and anticonvulsant activity of 2(3H)-benzoxazolone and 2(3H)- benzothiazolone derivatives
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A series of 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives were synthesized and evaluated for anticonvulsant activity. The compounds were assayed, intraperitoneally in mice and per os in rats, against seizures induced by maximal electroshock (MES) and pentylene-tetrazole (scMet). Neurologic deficity was evaluated by the rotarod test. The compounds were prepared to determine the relationship between the 2(3H)-benzoxazolone and 2(3H)-benzothiazolone derivatives' structures and anticonvulsant activity. Several of these compounds showed significant anticonvulsant activity. Compounds 43 and 45 were the most active of the series against MES-induced seizures with ED50 values of 8.7 and 7.6 mg/kg, respectively. Compound 45 displayed good protection against MES-induced seizures and low toxicity in rats with an oral ED50 of 18.6 mg/kg and a protective index (PI = TD50/ED50) of 1 receptors with nanomolar affinities.
- Ucar, Huseyin,Van Derpoorten, Kim,Cacciaguerra, Silvia,Spampinato, Santi,Stables, James P.,Depovere, Paul,Isa, Majed,Masereel, Bernard,Delarge, Jacques,Poupaert, Jacques H.
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p. 1138 - 1145
(2007/10/03)
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- ACYLATION OF 2,3-DIHYDROBENZOXAZOL-2-ONE IN A TWO STEPS METHOD INVOLVING AN ACYL MIGRATION
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A new method of acylation of 2,3-dihydrobenzoxazol-2-one 1 is proposed in a two-steps procedure involving an acyl migration.
- Cotelle, Nicole,Cotelle, Philippe,Lesieur, Daniel
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p. 3259 - 3266
(2007/10/02)
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