- Synthesis and antibiofilm evaluation of 3-hydroxy-2,3-dihydroquinazolin-4(1H)-one derivatives against opportunistic pathogen Acinetobacter baumannii
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The emergence of multidrug resistant microorganisms has triggered the impending need for new aitimicrobial strategies. The antivirulence strategy with the benefite of alleviating the drug resistance becomes the focus of research. In this study, 22 quorum sensing inhibitors were synthesized by mimicking the structure of autoinducer and acinetobactin and up to 34% biofilm inhibition was observed with 5u. The biofilm inhibition effect was further demonstrated with extracellular polysaccharides inhibition and synergism with Gentamycin sulphate.
- Yang, Guo,Cheng, Cheng,Xu, Guo-Bo,Tang, Lei,Chua, Kim-Lee,Yang, Yuan-Yong
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- An Experimental and Computational Approach to Understanding the Reactions of Acyl Nitroso Compounds in [4 + 2] Cycloadditions
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Catalytic aerobic oxidation of phenyl hydroxycarbamate 1 and 1-hydroxy-3-phenylurea 2 using CuCl2 and 2-ethyl-2-oxazoline in methanol gave acyl nitroso species in situ, which were trapped in nitroso-Diels-Alder (NDA) reactions with various dienes to afford the corresponding cycloadducts in high yields (90-98%). Competing ene products were also present for dienes containing both alkene π-bonds and allylic σ-bonds, and the ene yields are higher with 1 than with 2. The use of the chiral hydroxamic acid, (R)-1-hydroxy-3-(1-phenylethylurea) 3 (same conditions) gave NDA cycloadducts in high yields (97-99%) with no ene product from 2,3-dimethyl-1,3-butadiene. NDA cycloadducts were not obtained from other hydroxamic acid analogues [RCONHOH (R = PhCH2 4; Ph(CH2)2 5; Ph(CH2)3 6; Ph(CH2)4 7; Ph 8; 2-pyridyl 9; 3-pyridyl 10] with various dienes using copper-oxidation but rather were obtained using sodium periodate, resulting in variable NDA yields (13-51%) from hydroxamic acids 1-10 with cyclohexa-1,3-diene and 2,3-dimethyl-1,3-butadiene (several cycloadducts characterized by X-ray crystallography). The NDA and nitroso-ene reaction pathways of nitroso intermediates with dienes were mapped by DFT computations (B3LYP/6-31G), which showed that the acyl nitroso species are super-reactive and that activation energies in the NDA processes are lower than the isomerization barriers between some cis- and trans-butadienes.
- Chaiyaveij, Duangduan,Batsanov, Andrei S.,Fox, Mark A.,Marder, Todd B.,Whiting, Andrew
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p. 9518 - 9534
(2015/10/12)
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- Synthesis and anticancer activity of new hydroxamic acid containing 1,4-benzodiazepines
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By employing an intramolecular Pd(0)-mediated ring opening of an acylnitroso-derived cycloadduct, new hydroxamic acid containing benzodiazepines have been synthesized and have demonstrated biological activity in MCF-7 and PC-3 tumor cell lines. Subsequent
- Tardibono Jr., Lawrence P.,Miller, Marvin J.
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scheme or table
p. 1575 - 1578
(2009/09/06)
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- Synthesis and application of N-hydroxylamine derivatives as potential replacements for HOBt
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Several heterocycles containing N-hydroxylamine were prepared and tested as coupling additives to replace the use of N-hydroxybenzolriazole (HOBt.) derivatives. On the basis of our results on coupling yield and racemization-suppressing properties, we propose N-hydroxyindolin-2-one and 6- cfiloro-N-hydroxy-2-phenylbenzimidazole as suitable substitutes for HOBt. Wiley-VCH Verlag GmbH & Co. KGaA.
- El-Faham, Ayman,Albericio, Fernando
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supporting information; experimental part
p. 1499 - 1501
(2009/07/11)
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- Monohydroxamic acids and bridging dihydroxamic acids as chelators to ruthenium(iii) and as nitric oxide donors: Syntheses, speciation studies and nitric oxide releasing investigation
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The synthesis and spectroscopic characterisation of novel mononuclear RuIII(edta)(hydroxamato) complexes of general formula [Ru(H 2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-Cl and 3-Me-phenylhydroxamato), as well as the first example of a Ru III-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)] ·H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear RuIII complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(μ-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with RuIII, are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru III involves initial formation of RuIII-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of RuIII-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids. The Royal Society of Chemistry.
- Griffith, Darren,Krot, Krystyna,Comiskey, Jedd,Nolan, Kevin B.,Marmion, Celine J.
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p. 137 - 147
(2008/04/13)
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- Parallel synthesis and in vitro activity of novel anthranilic hydroxamate-based inhibitors of the prostaglandin H2 synthase peroxidase activity
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Currently available non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin are directed at the cyclooxygenase (COX) site, but not the peroxidase (POX) activity of prostaglandin H2 synthase (PGHS). They are thus unable to inhibit the free-radical induced tissue injury associated with PGHS peroxidase activity, which can occur independently of the COX site. A lead compound, anthranilic hydroxamic acid (AHA) was found to have significant PGHS-POX inhibitory activity (IC50 = 72 μM). To define the critical parameters for PGHS-POX inhibition, we investigated 29 AHA derivatives, synthesised from their acid precursors, using solid phase synthesis. In vitro analysis demonstrated a ten-fold improvement in inhibition with 3,5-diiodoanthranilic hydroxamic acid (IC50 = 7 μM). The Royal Society of Chemistry 2005.
- Lee, Jean,Chubb, Anthony J.,Moman, Edelmiro,McLoughlin, Brian M.,Sharkey, Caroline T.,Kelly, John G.,Nolan, Kevin B.,Devocelle, Marc,Fitzgerald, Desmond J.
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p. 3678 - 3685
(2007/10/03)
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- 3-HYDROXY-4-OXO-1,2,3-TRIAZINES AND DERIVATIVES THEREOF FOR AMIDE AND ESTER BOND FORMATION
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The present invention relates to the use of a compound of formula I as a coupling reagent in forming amide or ester bonds from a reaction between a carboxylic acid and an amine or an alcohol, respectively. The compounds of formula I are especially useful as coupling reagents in the preparation of peptide bonds during peptide synthesis. In particular, the compounds of formula I are useful in promoting the formation of reactive reaction intermediates, inhibiting side reactions and in suppression of racemization. In addition, the present invention provides novel compounds of Formula I, and salts of N-oxides thereof.
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- Hydroxamic acid and its derivatives as inhibitors of melanocyte tyrosinase for topical skin lighteners
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Methods, compounds, and formulations are provided to reduce pigmentation in mammalian skin, comprising hydroxamic acid and its derivatives, and especially benzohydroxamic acid and its derivatives. The compounds preferably inhibit pigment synthesis in melanocytes through inhibition of melanocyte tyrosinase. The methods can be used for lightening skin, and for treating uneven skin complexions, which result from hyperpigmentation-related medical conditions such as melasma, age spots, freckles, ochronosis, and lentigo. The compounds can be used medically or cosmetically, and preferably as topical formulations.
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- Novel 1,4-benzodiazepines from acylnitroso-derived hetero-Diels-Alder cycloadducts
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(matrix presented) N4-Hydroxy-1,4-benzodiazepines were synthesized in a single step from synthetically versatile acylnitroso-derived hetero-Diels-Alder cycloadducts. The efficiency of this transformation was found to be dependent on the NH pKa Of the cycloadduct sulfonamide.
- Surman, Matthew D.,Mulvihill, Mark J.,Miller, Marvin J.
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p. 139 - 141
(2007/10/03)
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- Therapeutic compounds for the treatment of asthma and allergy, and methods of use thereof
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The present invention relates to compounds capable of inhibiting leukotriene activity and histamine activity, and their use in treating asthma and allergic conditions such as hay fever, dermatitus, and urticaria. Inhibition of both pathways permits more effective treatment of conditions with fewer side effects than can be achieved using most available antihistamines alone.
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- A 15N NMR investigation of a series of benzotriazinones and related antitumour heterocycles
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A series of 3-substituted 1,2,3-benzotriazin-4-ones, 1 and 2, were synthesized by standard methods and the 15N NMR spectra were recorded. All spectra were obtained using the natural abundance of the nitrogen-15 isotope. The chemical shifts appear in the normal range for N-1, N-2 and N-3 of the triazine ring, and also correlate with the chemical shifts in the spectra of the imidazolotriazinone, 4, and the imidazolotetrazinone, 5. Significantly, the spectra of 1a, 2 and 4, recorded with full NOE, show inversion of the singlet assigned to N-3, demonstrating that these compounds exist in the tautomeric form shown. The structure of the 4-iminobenzotriazinone (3) was confirmed by this 15N NMR analysis. The spectrum shows a signal for the NH-bearing imino-nitrogen atom, which is an inverted singlet in the NOE spectrum, whereas the signal from the N-3 atom of 3 is not inverted in the NOE spectrum. Copyright
- Vaughan, Keith,Wilman, Derry E. V.,Wheelhouse, Richard T.,Stevens, Malcolm F. G.
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p. 300 - 302
(2007/10/03)
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- Compositions containing N-amino- and N-hydroxy-quinazolinones and methods for preparing libraries thereof
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The present invention is directed to certain N-amino- and N-hydroxy-quinazolinone compounds and synthetic methods for synthesis thereof, which compounds may find use in combinatorial libraries. More specifically, the invention is directed to the synthesis of 3-hydroxy- and 3-amino-4(1H)-quinazolinones via the reaction of an appropriate 2-aminobenzamide compound with a carboxylic acid or acyl halide at ambient temperature performed on a solid support or in solution.
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- Methods for synthesizing libraries of dihydro-quinazolinones
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Synthetic methods for solution and solid-phase synthesis of combinatorial libraries of dihydro-quinazolinones, including synthesis of 2,3-dihydro-3-alkoxy-4(1H)-quinazolinones or 2,3-dihydro-3-hydroxy-4(1H)-quinazolinones via the Lewis-acid catalyzed reaction of an appropriate 2-aminobenzamide with an aldehyde at ambient temperature performed on a solid support or in solution.
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- Copper(II) complexes of isomeric aminophenylhydroxamic acids. A novel 'clam-like' dimeric metallacrown and polymeric helical structure containing interlinked unique copper(II) sites
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The reaction of 3-aminophenylhydroxamic acid with CuSO4·5H2O in aqueous solution gives the novel helical polymer [Cu3(3-Apha)4(H2O)SO4] n·8H2O 1 the structure of which contains interlinked repeating units having three unique neutral, anionic and cationic copper(II) sites. In this complex the copper(II) sites are magnetically non-interacting. A similar reaction with 2-aminophenylhydroxamic acid gives the novel dimeric 'metallacrown' [Cu5(2-AphaH-1)4(μ-SO4)(H 2O)2]2·10H2O 2 which has a 'clam-like' structure showing strong antiferromagnetic behaviour. In contrast to the above ligands, 4-aminophenylhydroxamic acid gives the monomeric square planar complex Cu(4-Apha)2·H2O 3 which exhibits paramagnetic behaviour. Crystal structures of all three complexes are reported.
- Gaynor,Starikova,Haase,Nolan
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p. 1578 - 1581
(2007/10/03)
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- Hydroxamic acid and pharmaceutical preparations containing the same
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Hydroxamic acids, pharmaceutical preparations containing the same, new ω(2''-naphthoxy)-alkylhydroxamic acids as well as a process for their production are disclosed. The new compounds display antiasthmatic and further pharmacologically valuable characteristics. They are prepared by reacting the corresponding carboxylic acid ester or amide with hydroxylamine or its salt under the described conditions into compounds of Formula I,R--CO--NH--OH.The compounds of Formula I are useful in human and veterinary medicine as medicaments the active principal of which is the inhibition of lipoxygenase, thus as antiasthmatic, antianaphylactic, antiphlogistic, antirheumatic and antithrombotic preparations.
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- Facile Synthesis of Benzimidazol-2-one Derivatives by Modified Lossen Rearrangement
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A "formamide modification" has been applied to the Lossen rearrangement of several biologically important anthranilohydroxamic acids, some of them prepared for the first time.It has been found that a short heating at temperatures in the range 130-140 deg C converts these compounds into corresponding benzimidazol-2-ones with excellent yields.
- Eckstein, Zygmunt,Jadach, Tadeusz,Lipczynska-Kochany, Ewa
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p. 279 - 281
(2007/10/02)
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- Synthesis of hydroxy- and amino-substituted benzohydroxamic acids: Inhibition of ribonucleotide reductase and antitumor activity
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Benzohydroxamic acids inhibit mammalian ribonucleotide reductase and exhibit antineoplastic activity in L1210 leukemic mice. Five new hydroxy- and amino-substituted benzohydroxamic acids (3,4- and 3,5-OH,3,4-NH2, 2,3,4-, and 3,4,5-OH) were prepared and tested along with 12 previously reported benzohydroxamic acids (BHA) for enzyme inhibition and antitumor activity. The most potent enzyme inhibitor in this series was 2,3,4-OH-BHA (ID50=3.5 μM), which is 140 times more potent than hydroxyurea, but its toxicity limited the antitumor activity to a 30% increase in life span of L1210 bearing mice at 125 (mg/kg) day ip for 8 days. The most effective antitumor agent in this series was 3,4-OH-BHA which prolonged the life span of L1210 bearing mice 103% at 600 (mg/kg)/day ip for 8 days.
- van't Riet,Wampler,Elford
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p. 589 - 592
(2007/10/05)
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