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Lactams
Terms modified by Lactams Selected Abstracts1,6- and 1,7-naphthyridines.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2005A series of 8-hydroxy-1,6-naphthyridin-5(6H)-one-7-carboxamides 1 and the isomeric 5-hydroxy-1,7-naphthyridin-8(7H)-one-6-carboxamides 2 were synthesized. N -Lactam unsubstituted compounds 1a-c and 2a,b were obtained by alkoxide-induced rearrangement of the corresponding quinolinimidoacetamides 3. Compounds 1e,f and 2e,f were synthesized by heterocyclization of the corresponding quinolinamic esters 6 and 7. Spectroscopic properties (uv, ir, 1H and 13C nmr and ms) were analyzed and the proposed structures confirmed. [source] ChemInform Abstract: Copper Catalyzed Coupling of ,-Bromocarboxylate (III) with ,-Lactam (V).CHEMINFORM, Issue 23 2009Katerina Brychtova Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: Intramolecular Ene Reaction of a Chiral Bicyclic Lactam.CHEMINFORM, Issue 16 2009James E. Resek Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] A Facile Synthesis of 4-Gem-difluoromethylene ,-Lactam and Its Drivatives from BrCF2CF2Br.CHEMINFORM, Issue 4 2007Hui Wang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Improved Synthesis of 7,5-Fused Bicyclic Lactam for Use as Peptidomimetics.CHEMINFORM, Issue 36 2005Wesly Seide Abstract For Abstract see ChemInform Abstract in Full Text. [source] Simultaneous Assembly of the ,-Lactam and Thiazole Moiety by a New Multicomponent Reaction.CHEMINFORM, Issue 50 2002Juergen Kolb Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Controlling Factors in Chiral Bisoxazoline-Catalyzed Asymmetric Lithium Ester Enolate,Imine Condensation Producing a ,-Lactam.CHEMINFORM, Issue 11 2001Takeshi Kambara Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] CuI -Catalyzed Azide,Alkyne Intramolecular i -to-(i+4) Side-Chain-to-Side-Chain Cyclization Promotes the Formation of Helix-Like Secondary StructuresEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2010Mario Scrima Abstract A solid-phase assembly of model peptides derived from human parathyroid hormone-related protein (11,19) containing ,-azido- and ,-yl-,-amino acid residues in positions i and i+4 was cyclised in solution by an intramolecular CuI -catalyzed azide,alkyne 1,3-dipolar Huisgen cycloaddition. These series of heterodetic cyclo-nonapeptides varied in the size of the disubstituted 1,2,3-triazolyl-containing bridge, the location and the orientation of the 1,2,3-triazolyl moiety within the bridge. The 1,2,3-triazolyl moiety, presented at either 1,4- or 4,1-orientation, is flanked by side chains containing 1,4 CH2 groups that result in bridges comprised from 4,7 CH2 groups connecting residues 13 and 17. Comprehensive conformational analysis employing CD, NMR and molecular dynamics reveals the conformational propensities of these heterodetic cyclo-nonapeptides. Cyclo-nonapeptides containing either the 7 methylene bridge (VII and VIII) or the 4 methylene bridge (II) are unstructured in structure-promoting solvent. Cyclo-nonapeptide I in which the 1,4-disubstituted 1,2,3-triazolyl is flanked by 3 and 1 CH2 groups in proximity to the respective residues 13 and 17, is stabilized in a non-canonical structure. All the other heterodetic cyclo-nonapeptides (III,VI) in which the 1,2,3-triazolyl is flanked by a total of 5 or 6 CH2 groups nicely accommodate ,-helical structures and reproduce very closely the helical structure stabilized by the analogous cyclo-nonapeptide in which Lys13 and Asp17 are bridged by the isosteric lactam. These studies suggest that the bioorthogonal i -to-(i+4) side-chain-to-side-chain cyclization via the prototypic "click reaction" offers a new and powerful approach for generating stable helix mimetic structures. [source] Synthesis of 3- and 4-Hydroxy-2-aminocyclohexanecarboxylic Acids by IodocyclizationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2005Zsolt Szakonyi Abstract Starting from cis -7-azabicyclo[4.2.0]oct-4-en-8-one, novel routes have been developed for the synthesis of 2-amino-4-hydroxycyclohexanecarboxylic acid and its 3-hydroxy-substituted analog via iodooxazine, iodooxazoline or iodolactone intermediates. After CAL-B-catalyzed enzymatic transformation of the starting ,-lactam, the iodolactone method was applied to the synthesis of 3-hydroxy-substituted ,-amino acid enantiomers. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] The 15N-CPMAS spectra of simazine and its metabolites: measurements and quantum chemical calculationsEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 4 2007A. E. Berns Summary DFT calculations are a powerful tool to support NMR studies of xenobiotics such as decomposition studies in soil. They can help interpret spectra of bound residues, for example, by predicting shifts for possible model bonds. The described bound-residue models supported the hypothesis of a free amino side chain already suspected by comparison with the experimental data of the standards. No match was found between the calculated shifts of amide bondings of the amino side chains (free or substituted) and the experimental NMR shifts of a previous study. In the present paper, first-principles quantum chemical calculations were used to support and check the interpretation of the 15N cross polarization-magic angle spinning nuclear magnetic resonance (15N-CPMAS NMR) spectra of simazine and its metabolites. Density functional theory (DFT) calculations were performed using Gaussian 03 and the nuclear magnetic shielding tensors were calculated using the Gauge-Independent Atomic Orbital (GIAO) method and B3LYP/6,311+G(2d,p) model chemistry. Good agreement was reached between the calculated and measured chemical shifts of the core nitrogens and the lactam and lactim forms of the hydroxylated metabolites could be clearly distinguished. The calculated spectra showed that these metabolites exist preferentially in the lactam form, an important fact when considering the possible interactions of such hydroxylated metabolites with the soil matrix. Although the calculated bound-residue models in the present study only partly matched the experimental data, they were nevertheless useful in helping to interpret the experimental NMR results of a previous study. To get a better match between the calculated and the measured shifts of the side-chain nitrogens the calculations need to be further developed, taking into account the influence of neighbouring molecules in the solid state. Altogether, quantum chemical calculations are very helpful in the interpretation of NMR spectra. In the future, they can also be very useful for the prediction of NMR shifts, in particular when it is not possible to measure the metabolites due to a lack of material or in cases where practical experiments cannot be conducted. [source] Synthesis of 2-Azabicyclo[3.2.2]nonane-Derived Monosaccharide Mimics and Their Evaluation as Glycosidase InhibitorsHELVETICA CHIMICA ACTA, Issue 3 2006Stephan Buser Abstract The racemic 2-azabicyclo[3.2.2]nonanes 5 and 18 were synthesized and tested as , -glycosidase inhibitors. The intramolecular Diels,Alder reaction of the masked o -benzoquinone generated from 2-(allyloxy)phenol (6) gave the , -keto acetal 7 which was reduced with SmI2 to the hydroxy ketone 8. Dihydroxylation, isopropylidenation (,,12), and Beckmann rearrangement provided lactam 15. N -Benzylation of this lactam, reduction to the amine 17, and deprotection provided the amino triol 19 which was debenzylated to the secondary amine 5. Both 5 and 19 proved weak inhibitors of snail , -mannosidase (IC50,>,10,mM), Caldocellum saccharolyticum , -glucosidase (IC50,>,10,mM), sweet almond , -glucosidase (IC50,>,10,mM), yeast , -glucosidase (5: IC50,>,10,mM; 19: IC50,=,1.2,mM), and Jack bean , -mannosidase (no inhibition detected). [source] A Concise Route to Racemic Anatoxin a from Cycloocta-1,5-dieneHELVETICA CHIMICA ACTA, Issue 1 2006Tse-Lok Ho Abstract The synthesis of racemic anatoxin a (1a) from cycloocta-1,5-diene via its 1,:,1 cycloadduct with N -chlorosulfonyl isocyanate is described. The N -unsubstituted , -lactam 2b was converted to a , -amino ester 3 which was then submitted to a Pd-catalyzed cyclization to afford the conjugated ester 4a. The N -tosyl derivative 4b was then elaborated into N -tosylanatoxin a (1b) via a Weinreb amide. [source] Antimicrobial therapy in DermatologyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2006Cord Sunderkötter Antiseptika; Antibiotika; ,-Laktam-Resistenz; Weichteilinfektion Summary The extensive and sometimes indiscriminate use of antibiotics sometimes without strict indications has led to increases in both bacterial resistance and sensitization of patients. Systemic antibiotics in skin infections are indicated when a severe local infection occurs which spreads into the surrounding tissue or when there are signs of systemic infection. There are special indications in patients with peripheral arterial occlusive disease,diabetes or immunosuppression. Topical use of antibiotics should be abandoned and replaced by antiseptics. The ,-lactam antibiotics are the antibiotics of first choice for many skin infections. They are usually effective, have a well-defined profile of adverse events and most are affordable. Penicillin G or V are the first line treatment for erysipelas. Infections with Staphylococcus aureus are usually treated with isoxazolyl penicillins or second generation cephalosporins. In mixed infections in patients with diabetes or peripheral arterial occlusive disease,the treatment of choice is metronidazole plus ,-lactam-/,-lactamase inhibitor antibiotics, but quinolones or second generation cephalosporins can also be used, once again with metronidazole. The aim of this review is to define the indications for antibiotics in dermatology, to highlight their modes of action and adverse effects and to make suggestions for rational antibiotic therapy in cutaneous infections frequently encountered in the practice of dermatology. Zusammenfassung Der bisweilen unkritische Einsatz von Antibiotika hat die Resistenzentwicklung beschleunigt und die Sensibilisierungsrate bei Patienten erhöht. Systemische Antibiotika sind bei kutanen Superinfektionen in der Regel dann indiziert, wenn eine schwere lokale Infektion mit Ausbreitung in das umgebende Gewebe vorliegt oder wenn sich gleichzeitig Zeichen einer systemischen Infektion einstellen. Bei peripherer arterieller Verschlusskrankheit, Diabetes mellitus oder Immunsuppression kann die Indikation auch früher gestellt werden. Lokale Antibiotika sollten in der Regel gemieden und durch moderne Antiseptika ersetzt werden. ,-Laktam-Antibiotika stellen für viele bakterielle Infektionserkrankungen in der ambulanten und klinischen Dermatologie die Antibiotika der ersten Wahl dar. Sie sind häufig ausreichend wirksam, besitzen ein gut definiertes Nebenwir-kungsprofil und sind zumeist preisgünstig. So wird das klassische Streptokokken-Erysipel mit Penicillin G oder V therapiert, bei Infektionen durch S. aureus kommen primär Isoxazolyl-Penicilline oder Zweit-Generations-Cephalosporine zum Einsatz. Im Falle von Mischinfektionen bei Diabetes mellitus oder pAVK sind ,-Laktam/,-Laktamaseinhibitoren indiziert, alternativ auch Chinolone oder Zweitgenerations-Cephalosporine, jeweils in Kombination mit Metronidazol. Diese Übersicht möchte die Indikationen für Antibiotika in der Dermatologie aufzeigen, das Wichtigste zu deren Wirkungsweise und Nebenwirkungen aufzählen und Therapievorschläge für häufige Infektionen der Haut in der dermatologischen Praxis geben. [source] Antibiotic-resistant Gram-negative bacteria in a virtually closed water reticulation systemJOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2000S.G. Mulamattathil The effect of the effluent from a chicken meat-processing plant on the antibiotic-resistant bacterial profile was investigated in an almost closed water reticulation system. Of the 273 faecal coliform isolates 256 (93%) were resistant to one or more of the eight antibiotics tested. The most prevalent isolates were for the ,-lactam antibiotics ampicillin and cephalothin followed by the sulphonamides sulphatriad and cotrimoxazole. Eleven different resistance patterns were identified with a single pattern, comprising of ampicillin-, cephalothin-, streptomycin-, sulphatriad-, cotrimoxazole- and tetracyclin-resistant isolates, dominating the meat-processing effluent. An apparent correlation was observed between the specific use of certain antibiotics and the prevalence of the corresponding resistant bacterial isolates. The drugs used to treat the occasional infections, belonging to the ,-lactam and sulphonamide group of antibiotics, seemed to have a more pronounced effect on the antibiotic-resistant bacterial profile in the primary water source than those drugs used as feed additives, oxytetracyclin and the aminoglycoside flavomycin. [source] Full Characterization and some reactions of 1-(2-adamantyl)-3-(1-adamantyl)aziridin-2-oneJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2008István Lengyel We found that 1-(2-adamantyl)-3- tert -butylaziridin-2-one (5a) is unstable. It slowly decomposes at room temperature, although detectable by IR spectroscopy (1840 cm,1 band in CCl4). On the other hand, a closely related analogue, 1-(2-adamantyl)-3-(1-adamantyl)aziridin-2-one (5b), is very stable, in concurrence with an earlier report [1]. We fully characterized aziridinone 5b, identified its thermal decomposition products (7 and 8) and reacted it with two aprotic ionic (tBuO, and HO,) and one protic non-ionic nucleophile (benzylamine). All three products (9b, 10, and 11) result from exclusive cleavage of the lactam (1-2) bond. [source] A novel synthesis of cyclopropyl lactam and amide from cis -2-aryl-3-benzoyl-1,1-dicynocyclopropane with H2O2 in the presence of NaHCO3JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2007Zhongjiao Ren The process for preparation of cyclopropyl lactam and amide from cis -2-aryl-3-benzoyl-1,1-dicynocyclopropane with H2O2 in the Presence of NaHCO3 is described. The highly stereoselective conversion of monocyano group to amide has been carried out in the present method. [source] Cycloaddition reaction of schiff bases with ketenes generated by pyrolysis of 2-aryl-substituted 1,5,7-trioxaspiro[2.5]octane-4,8-dionesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2006Takashi Tsuno The ,-oxo ketenes 6 which are generated by the pyrolysis of the 2-aryl-substituted 1,5,7-trioxaspiro[2.5]octane-4,8-diones 1, were reacted with Schiff bases 2 to give spiro compounds constructed between the ,-lactam and 1,3-dioxolan-4-one; i.e., the 2,3,6-triaryl-2-aza-5,7-dioxaspiro[3.4]octane-1,8-diones 3 and 4. Hydrogenation of the mixture of 3a and 4a in the presence of catalytic amount of Pd-C produced the trans -2-benzyloxy-1,4-diphenyl-,-lactam-3-carboxylic acid 9. [source] Evaluation of N -hydroxymethylphthalimide in alkaline medium: Novel entry to the tricyclic [1,3]oxazepine core via an intramolecular , and O -cationic cyclizationJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2003Armelle Cul Fused isoindolo[1,3]benzo(or thieno)oxazepines 8a,b and one of their positional isomers aromatic tricyclic N,O -acetals 13b are reported to occur efficiently in a three-step sequence from N -hydroxy-methylphthalimide (6). The key step of this methodology is the intramolecular arylation of an endocyclic and/or exocyclic N -acyliminium cation. The mechanism leading to these species, in particular to a tricyclic lactam 13b, is discussed. [source] A flexible approach to the design of new potent substance P receptor ligandsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2001R. Millet The development of small-molecule antagonists of the substance-P-preferring tachykinin NK1 receptor offers an excellent opportunity to exploit these molecules as novel therapeutic agents in diverse pathologies such as depression, emesis or asthma. GR71251 has previously been identified as a potent and selective substance-P-receptor antagonist. We have therefore undertaken the synthesis of new pseudopeptidic analogues based on the C-terminal sequence of GR71251. The evaluation of binding affinities toward NK1 and NK2 receptors has enabled us to propose new selective NK1 ligands with high affinity. Structure-activity relationships showed that the Trp-OBzl(CF3)2 moiety is essential for NK1 affinity and that the introduction of building units such as spirolactam, lactam or proline, leading to a constrained peptide, increased selectivity for NK1 receptors. These compounds constitute a useful starting point for new substance P antagonists and represent an attractive lead series for further studies on the design of specific NK1 antagonists. [source] Amide and lactam hydrolysis of N -(2-hydroxyacetyl)-2-pyrrolidone: effective catalysis,JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2006Lisaedy García Borboa Abstract When N -(2-hydroxyacetyl)-2-pyrrolidone (open form) is dissolved in water at pH,>,8, irreversible cleavage of the exocyclic and endocyclic amide CN bond occurs. The latter rupture corresponds to the lactam opening yielding N -(4-hydroxyacetyl)butanoic acid (NBA). NBA is produced from the ester hydrolysis of the ester-amide macrocycle that is in equilibrium with the cyclol form of the open form. We have previously reported this latter equilibrium for N -(2-aminoacetyl)-2-lactams. 2-pyrrolidone (lactam) and glycolic acid are produced from direct hydrolysis of the open form by means of the amide exocyclic cleavage. The [NBA]/[lactam] ratio increases at higher pH since the NBA production is second order with respect to [OH,] while the corresponding lactam formation is only first order. The obtained kobs is hence the sum of the rate constants that yield lactam and NBA, respectively. This kobs is uncatalyzed and specific base catalyzed with unusually high rate constants of 2.1,×,10,6,s,1 and 0.025,M,1,s,1, respectively. The stability of the corresponding tetrahedral intermediate formed and the intramolecular alkoxy nucleophilic attack on the lactam carbonyl group combined with an effective protonation of the lactam nitrogen that promotes the CN cleavage, contribute to increase the reaction rates and lactam opening. Rate constants for the two parallel reactions are obtained from kobs and [NBA]/[lactam] versus pH plots. Copyright © 2006 John Wiley & Sons, Ltd. [source] The ,-lactam-sensitive d,d -carboxypeptidase activity of Pbp4 controls the l,d and d,d transpeptidation pathways in Corynebacterium jeikeiumMOLECULAR MICROBIOLOGY, Issue 3 2009Marie Lavollay Summary Corynebacterium jeikeium is an emerging nosocomial pathogen responsible for vascular catheters infections, prosthetic endocarditis and septicemia. The treatment of C. jeikeium infections is complicated by the multiresistance of clinical isolates to antibiotics, in particular to ,-lactams, the most broadly used class of antibiotics. To gain insight into the mechanism of ,-lactam resistance, we have determined the structure of the peptidoglycan and shown that C. jeikeium has the dual capacity to catalyse formation of cross-links generated by transpeptidases of the d,d and l,d specificities. Two ampicillin-insensitive cross-linking enzymes were identified, LdtCjk1, a member of the active site cysteine l,d -transpeptidase family, and Pbp2c, a low-affinity class B penicillin-binding protein (PBP). In the absence of ,-lactam, the PBPs and the l,d -transpeptidase contributed to the formation of 62% and 38% of the cross-links respectively. Although LdtCjk1 and Pbp2C were not inhibited by ampicillin, the participation of the l,d -transpeptidase to peptidoglycan cross-linking decreased in the presence of the drug. The specificity of LdtCjk1 for acyl donors containing a tetrapeptide stem accounts for this effect of ampicillin since the essential substrate of LdtCjk1 was produced by an ampicillin-sensitive d,d -carboxypeptidase (Pbp4Cjk). Acquisition and mutational alterations of pbp2C accounted for high-level ,-lactam resistance in C. jeikeium. [source] P450-catalyzed vs. electrochemical oxidation of haloperidol studied by ultra-performance liquid chromatography/electrospray ionization mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 9 2010Tove Johansson Mali'n The metabolites formed via the major metabolic pathways of haloperidol in liver microsomes, N -dealkylation and ring oxidation to the pyridinium species, were produced by electrochemical oxidation and characterized by ultra-performance liquid chromatography/electrospray ionization mass spectrometry (UPLC/ESI-MS). Liver microsomal incubations and electrochemical oxidation in the presence of potassium cyanide (KCN) resulted in two diastereomeric cyano adducts, proposed to be generated from trapping of the endocyclic iminium species of haloperidol. Electrochemical oxidation of haloperidol in the presence of KCN gave a third isomeric cyano adduct, resulting from trapping of the exocyclic iminium species of haloperidol. In the electrochemical experiments, addition of KCN almost completely blocked the formation of the major oxidation products, namely the N -dealkylated products, the pyridinium species and a putative lactam. This major shift in product formation by electrochemical oxidation was not observed for the liver microsomal incubations where the N -dealkylation and the pyridinium species were the major metabolites also in the presence of KCN. The previously not observed dihydropyridinium species of haloperidol was detected in the samples, both from electrochemical oxidation and the liver microsomal incubations, in the presence of KCN. The presence of the dihydropyridinium species and the absence of the corresponding cyano adduct lead to the speculation that an unstable cyano adduct was formed, but that cyanide was eliminated to regenerate the stable conjugated system. The formation of the exocyclic cyano adduct in the electrochemical experiments but not in the liver microsomal incubations suggests that the exocyclic iminium intermediate, obligatory in the electrochemically mediated N -dealkylation, may not be formed in the P450-catalyzed reaction. Copyright © 2010 John Wiley & Sons, Ltd. [source] Toward the development of new medicinal leads with selectivity for protein kinase C isozymesTHE CHEMICAL RECORD, Issue 4 2005Kazuhiro Irie Abstract Tumor promoters such as phorbol esters bind strongly to protein kinase C (PKC) isozymes to induce their activation. Since each PKC isozyme is involved in diverse biological events in addition to tumor promotion, the isozymes serve as promising therapeutic targets. Tumor promoters bind to the C1A and/or C1B domain of conventional (,, ,I, ,II, and ,) and novel PKC isozymes (,, ,, ,, and ,). As these C1 domains play differential roles in PKC activation and their translocation in cells, the development of agents with binding selectivity for individual C1 domains is a pressing need. For this purpose, we established a synthetic C1 peptide library of all PKC isozymes. The library enabled us to identify indolactam-V (1) as a promising lead compound. Our diverse structure,activity studies on 1 indicated that the position of the hydrophobic substituent on the indole ring dominates the PKC isozyme- and C1 domain-selective binding rather than conformation of the nine-membered lactam. Moreover, we suggested that the indole ring of 1 could be involved in the CH/, interaction with Pro-11 of the C1B domain of PKC,. This invaluable information will lead to the structural optimization of the PKC, ligand as exemplified by the design and synthesis of naphtholactam-V8 (21). © 2005 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 5: 185,195; 2005: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20044 [source] Sinus Tissue Pharmacokinetics After Oral Administration of Amoxicillin/Clavulanic AcidTHE LARYNGOSCOPE, Issue 6 2000Paulo Borges Dinis MD Abstract Objectives The in vitro synergy of the amoxicillin/clavulanic acid combination has not always translated in vivo into clinical superiority compared with amoxicillin alone. Specifically, conflicting reports have disputed the superiority of the combination in the treatment of both acute otitis media and acute sinusitis. One possible reason for this may have to do with inadequate target tissue pharmacokinetics. To explore this possibility in the sinuses, we undertook the present investigation. Study Design A randomized, open, single-dose, sinus tissue pharmacokinetic study with oral amoxicillin/clavulanic acid. Methods Twenty-three adult patients with chronic rhinosinusitis who had been selected for surgery were randomly allocated to receive a tablet of 875/125 mg amo-icillin/clavulanate 2 to 4 hours before surgery began. During the operation tissue samples were collected at specific sinonasal sites for determination of both amo-icillin and clavulanic acid concentration levels. Results Amoxicillin displayed adequate tissue levels throughout the sinuses, high enough to cover common susceptible pathogens. However, the presence of clavulanate was detected in only half of the sinonasal tissue samples. Conclusions The kinetics of oral clavulanic acid apparently fails to provide a widespread anti,,-lactamase activity capable of enhancing the activity of amoxicillin in all parts of the sinuses. Despite this, amoxicillin/clavulanic acid maintains a central role in the treatment of acute rhinosinusitis, because amoxicillin is still the most effective oral ,-lactam against Streptococcus pneumoniae, a particularly virulent and increasingly resistant upper respiratory tract pathogen. Also, as our data show, a concomitant anti,,-lactamase activity can be expected to occur, although in an unpredictable fashion. [source] Common Inhibition of Both ,-Glucosidases and ,-Mannosidases by Isofagomine Lactam Reflects Different Conformational Itineraries for Pyranoside HydrolysisCHEMBIOCHEM, Issue 11 2004Florence Vincent Dr. Glycosidase inhibition is a key process both in the pursuit of new therapeutic agents and in the drive to understand transition-state stabilisation by these remarkable enzymes. That isofagomine lactam (1) is an equally potent inhibitor of ,-glucosidases and ,-mannosidases (despite possessing a carbonyl group) adds to the emerging view that mannosidases and glucosidases harness distinct transition states; the B2,5 conformation for some retaining mannosidases and the 4H3 for glucosidases, both of which place O2 pseudo-equatorially. [source] Domino Metal-Free Allene-,-lactam-Based Access to Functionalized Pyrroles.CHEMINFORM, Issue 46 2006Benito Alcaide Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Base-Induced Sequential Cyclization,Rearrangement of Enantioenriched 3-Aminoalkanoates to Five- and Seven-Membered LactamsCHEMISTRY - AN ASIAN JOURNAL, Issue 8-9 2008Takeo Sakai Abstract By treatment with tBuLi, linear 3-aminoalkanoates (4) were converted stereoselectively into five- and seven-membered lactams (trans- 5 and cis- 6). Initial cyclization to azetidin-2-one with subsequent aza-[1,2] and [2,3] rearrangement is the probable mechanistic pathway from 4 to 5 and 6. Although enantioenriched 4 was converted into nearly racemic 5 and 6, a linear 3-amino-2-methylalkanoate (17) with 90,%,ee bearing chirality at the ester ,-position afforded an all- cis seven-membered lactam (18) bearing three asymmetric centers with 85,%,ee. [source] Oral challenges are needed in the diagnosis of ,-lactam hypersensitivityCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2008P. J. Bousquet Summary Background ,-lactams continue to remain the most commonly involved drug family in allergic drug reactions. They are often essential and there is a cost-effective and favourable risk-benefit ratio for the exploration of all suspicions of ,-lactam allergy. A firm diagnosis is always based on skin tests and sometimes on provocation tests. Recommendations have been published by allergy societies and distinguished scientists but they are not always concordant and can lead to some confusion for the practicing allergologist. The situation has even worsened since the world wide withdrawal of these penicillin determinants and since the predominance of amoxicillin and cephalosporin prescriptions in most countries. Objective , Method In a recent article, it was stated that patients with a penicillin allergy history and negative skin tests to major and minor penicillin determinants are at a low risk of relapse (0,5%) when receiving a ,-lactam. In this paper, our Drug Allergy and Hypersensitivity Database, a cohort database, was used to demonstrate that this statement is false. Standardized European Network for Drug Allergy questionnaires, skin test and challenge procedures were followed. Results One-thousand two-hundred and eighteen subjects, 69.8% of female, 51.7% of atopics, were included. 21.1% had a true ,-lactam allergy confirmed by skin tests (178, 69.3%) or by drug provocation (79, 30.7%). 17.4% of the patients with negative skin tests to major and minor penicillin determinants were positive for a ,-lactam. Conclusion In the diagnosis of ,-lactams allergy, if all skin tests are negative, skin tests with other determinants and provocation tests under strict surveillance are mandatory. [source] A Theoretical Study on the Reactivity of a Rhenium Hydroxo-Carbonyl Complex Towards ,-LactamsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 29 2008Violeta Yeguas Abstract The mechanism of the reaction between the complex [Re(OH)(CO)3(N2C2H4)] and azetidin-2-one or 3-formylamino- N -sulfonatoazetidin-2-one was investigated by using the B3LYP density functional theory methodology in conjunction with the PCM-UAHF model to take into account solvent effects. According to our calculations, the rate-determining energy barrier for the azetidin-2-one case of 38.8 kcal,mol,1, becomes 25.7 kcal,mol,1 in the case of the 3-formylamino- N -sulfonatoazetidin-2-one species. The presence of the sulfonato group is crucial for the cleavage of the ,-lactam N1,C2 bond by the Re complex thanks to the interaction of the sulfonato group with the hydroxy and bidentate ligands of the complex. This could be of interest for the synthesis of ,-amino acids and their derivatives from ,-lactams under mild conditions and in solvents of low polarity promoted by organometallic complexes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Facile Synthesis of Selenium-Containing Bicyclic ,-Lactams through Enyne MetathesisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 14 2010Deepali B. Bankar Abstract Novel selenium-containing bicyclic ,-lactams were obtained through stereoselective insertion of (but-3-enyl)seleno and propargylseleno moieties at the C(4) positions of azetidinones with subsequent ring-closing enyne metathesis. [source] | ||||||||||||||||||||||||||||||||||