bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mehrcyclische Azine mit Heteroatomen in 1‐ und 3‐Stellung. 41. Mitt. Synthese heterocyclischer Immunmodulatoren. 3. Mitt.: Darstellung von N‐1‐substituierten 3‐(2‐Mercaptoethyl)chinazolin‐2,4(1H,3H)‐dionen über Bis[2‐(2‐amino‐benzoylamino)ethyl]disulfane und Prüfung auf immunstimulatorische Wirksamkeit
Authors: Gütchow Michael , Drößler Karl , Leistner Siegfried 
Published: October 2006

AbstractZur Darstellung von substituierten 3‐(2‐Mercaptoethyl)chinazolin‐2,4(1H,3H)‐dionen 4 wurde eine 3‐Stufen‐Synthese, ausgehend von substituierten Isatosäureanhydriden 1 beschritten. Die Reaktion von 1 mit Cystamin liefert Bis[2‐(2‐aminobenzoylamino)ethyl]disulfane 2. Umsetzung von 2 mit Chlorameisensäureethylester und nachfolgende Reduktion der heterocyclischen Disulfane 3 gibt die Mercaptoethylchinazolin‐2,4‐dione 4a–f. Die am N‐1 methyl‐ bzw. benzylsubstituierten Derivate 4b und 4c zeigten immunstimulatorische Wirksamkeit in verschiedenen Tests.
Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XXVI: Antiplatelet and Antithrombotic Effects of the Oligoamine RE 1492 in Combination with Standard and Future Antithrombotic Drugs
Authors: Rehse Klaus , Ciborski Thomas 
Published: October 2006

AbstractThe combined effects of the oligoamine RE 1492 with the NO‐donor RE 2047 or ASA, ticlopidine, pentoxifylline and BM 14515 were determined in vitro (Born‐test and in vivo (rat thrombosis model). The effects in vitro were supra additive but over independent. In vivo all combinations showed over additive and over independent inhibition of thrombus formation. The best results were obtained with a combination of 10 mg/kg RE 1492C and 10 mg/kg RE 2047. It inhibited thrombus formation in arterioles (A) by 79 % and 36 % in venoles (V). The combined effect of RE 1492C and pentoxifylline 10 mg/kg each was 62% (A) or 32% (V), respectively.
Preparation of 2‐Isotriurets by the Reaction between N,N‐Dialkyl‐O‐phenyl‐isoureas and Phenyl Isocyanate
Authors: Höppner Thomas , Schweim Harald G. 
Published: October 2006

AbstractDie Umsetzung von Phenylisocyanat (1a) mit N,N‐Diethyl‐O‐phenyl‐isoharnstoff (2a) führt bei Raumtemp. durch Übertragung eines HNCO‐Fragments zum 2‐Isotriuret 4a und N,N‐Dialkyl‐N,O‐diaryl‐isoharnstoff (5). Die Darstellung des erwarteten Additionsprodukts—des Carbamoylisoharnstoffs 3a — gelang bei Durchführung der Reaktion bei −60°C. Die Bildung von 2‐Isotriureten konnte nur bei N,N‐Diaryl‐O‐phenyl‐isoharnstoffen beobachtet werden. Für den Reaktionsablauf wird die Bildung einer cyclischen Zwischenstufe postuliert.Seit einiger Zeit befassen wir uns mit Additionsprodukten aus Isocyanaten 1 und Verbindungen mit festgelegter Iminopartialstruktur als potentielle Isocyanatpräcursoren1,2). In diesem Zusammenhang wurde von uns auch die Verbindungsklasse der Isoharnstoffe 2 als Additionskomponente untersucht.Carbamoylisoharnstoffe 3 sind seit Beginn dieses Jahrhunderts bekannt3,4). Durch Reaktion von Alkyl‐ und Arylisocyanaten mit substituierten Isoharnstoffen, die mindestens ein bewegliches H‐Atom aufweisen, sind die Carbamoylisoharnstoffe in großer Variationsbreite zugänglich. Aus Wirksamkeitsüberlegungen bei arylsubstituierten Derivaten2) interessierten uns die N,N‐dialkyl‐O‐phenyl‐substituierten Isoharnstoffe und deren Umsetzungsprodukte mit Isocyanaten.
Azines and Diazines as Potential Histamine H3‐Receptor Antagonists
Authors: Kieć‐Kononowicz Katarzyna , Ligneau Xavier , Stark Holger , Schwartz Jean‐Charles , Schunack Walter 
Published: October 2006

AbstractIn search of structure‐activity relationships among histamine H3‐receptor antagonists the imidazole ring of known H3‐receptor antagonists was replaced by different heteroaromatic ring systems. Thus, azines and diazines with ether (6–13) and carbamate (15–24) moieties as functional groups were synthesized. The obtained compounds did not show significant H3‐receptor antagonist activity in vitro (rat brain cortex) or in vivo (mice brain). The new compounds were also screened for H1‐receptor antagonist activity on the isolated guinea‐pig ileum and for H2‐receptor antagonist activity on the isolated spontaneously beating guinea‐pig right atrium. The substances showed only weak antagonistic activity at both histamine receptors, H1 and H2.
Untersuchungen an 1,4‐Naphthochinonen, 25. Mitt. Reaktion des Redox 5‐Lipoxygenase‐Inhibitors 2‐(3,5‐Di‐tert‐butyl‐4‐hydroxyphenyl)‐3‐hydroxy‐1,4‐naphthochinon mit O2•− und 3O2
Authors: Wurm Gotthard , Damerau Werner , Duchstein Hans‐Jürgen 
Published: October 2006

AbstractDer 5‐Lipoxygenase‐Inhibitor 2‐(3,5‐Di‐tert‐butyl‐4‐hydroxyphenyl)‐3‐hydroxy‐1,4‐naphthochinon (2), sein Deoxygenierungsprodukt 1 sowie die oxygenierte Spezies 3 sind O2•− ‐ Quencher unterschiedlicher Potenz in wäßriger Lösung. In alkoholischer Lösung ändert sich die antioxidative Aktivität von 1 nicht, 2 allerdings ist nur noch ein schwacher O2•− ‐ Quencher und 3 zeigt prooxidative Eigenschaften. Dieses Phänomen wurde in dem O2•− ‐generierenden Oxygenierungssystem (OS)DMSO‐CO32‐O2 mit präparativer Technik untersucht. Dabei konnte folgende Reaktionssequenz bewiesen werden: 3 ⇒ 2 ⇒ 4 (2,6‐Di‐tert‐butyl‐1,4‐benzochinon). Während der Schritt 3 ⇒ 2 |O2•− abhängig sein sollte, erfolgt der Übergang 2 ⇒ 4 in zwei Stufen. Die 1. Stufe ist eine Retro‐Michael reaktion unter Freisetzung von 2,6‐Di‐tert‐butylphenol (5), die 2. Stufe (5 ⇒ 4) beinhaltet die basenkatalysierte Oxygenierung mit 3O2. Das als Nebenprodukt anfallende Diphenochinon 6 kann – im Gegensatz zur Reaktion mit 1O2 – mit dem OS in beträchtlicher Ausbeute zu 4 gespalten werden.
Reduction of the Estrogenic Side Effects of the Mammary Tumor‐Inhibiting Drug [1,2‐Bis(2,6‐dichloro‐4‐hydroxyphenyl)‐ethylenediamine]dichloroplatinum(II) by Variation of Ring Substituents
Authors: Gust Ronald , Karl Johann , Faderl Michael , Schönenberger Helmut 
Published: October 2006

Abstract[1,2‐Bis(4‐methoxy/4‐hydroxyphenyl)ethylenediamine]dichloroplatinum‐(II) complexes with Cl‐, CH3‐, or OCH3‐substituents in the ortho‐positions of the aromatic rings (meso‐1‐PtCl2, D,L‐1‐PtCl2, meso‐2‐PtCl2, D,L‐2‐PtCl2, meso‐3‐PtCl2, meso‐4‐PtCl2, meso‐5‐PtCl2) were tested on the MDA‐MB 231 breast cancer cell line, the lymphocytic leukemia P388, and the estrogen receptor‐positive and ‐negative MXT mammary carcinoma of the mouse (MXT,ER(+)‐MC, MXT,ER(−)‐MC). The comparison of the effects of methoxy‐substituted complexes (meso‐1‐PtCl2, D,L‐1‐PtCl2, meso‐3‐PtCl2) with those of the respective hydroxy‐substituted ones (meso‐2‐PtCl2, D,L‐2‐PtCl2, meso‐4‐PtCl2) shows that a reduction of estrogenic effects as well as a total loss of the mammary tumor‐inhibiting activity takes place on methylation of the 4‐OH group. The exchange of the 2,6‐standing chlorine atoms by methyl groups in meso‐2‐PtCl2 led to the non‐estrogenic, but on the MXT,ER(+)‐MC highly effective derivative meso‐4‐PtCl2 which proved to be also cytotoxic on ER(−)‐tumors such as MXT,ER(−)‐MC, and the P 388 leukemia.
Synthesis of (±), (+), and (−)3β‐(1‐Phenylethylamino)cholest‐5,6‐enes
Authors: Anand Jasbir K. , Boyce Sam F. 
Published: October 2006

AbstractTwo diastereomeric derivatives of 3β‐(1‐phenylethylamino)cholest‐5,6‐enes, viz. R(+) 7b and S,(−) 7c have been synthesized by the reaction of racemic 1‐phenylethylamine 1a and cholesteryl p‐toluenesulfonate 2. The two isomers 7b and 7c separable by crystallization or by chromatography, were obtained in the ratio of 1:1.5 respectively, resulting in 20 % diastereomeric excess of product 7c. The authenticity of diastereomers 7b and 7c was established by obtaining them from the reactions of 2 with R(+) 1b and S(−) 1c enantiomers of 1‐phenylethylamine.Besides the steroidal amines (±) 7a, (+) 7b, and (±) 7c, optically enriched mixtures of 1,3‐diphenyl‐1‐butanone 4a were also obtained from these reactions.
Lipoxygenase‐Inhibitoren, 4. Mitt.: Synthese und Cyclisierungsreaktionen offenkettiger N1‐arylsubstituierter Amidrazone
Authors: Frohberg Petra , Kupfer Cornelia , Stenger Peter , Baumeister Ute , Nuhn Peter 
Published: October 2006

AbstractAusgehend von α‐Carbonylcarbonsäurearylhydrazonochloriden, die durch Japp‐Klingemann‐Spaltung erhalten werden, werden α‐Carbonylcarbonsäurearylhydrazonoamide,‐ester sowie ‐thioester synthetisiert, deren inhibitorische Wirkung gegenüber 15‐ bzw. 5‐Lipoxygenase beschrieben wird. Umsetzungen der Amidrazonderivate mit Formaldehyd führen zu Triazol‐,Triazolin‐ und in unerwarteter Weise zu Benzotriazepinderivaten.
Eine bequeme Synthese von 2‐Aryl‐2‐vinyl‐[1,3]‐dioxolanen und ‐dioxanen
Authors: Gutzmann Jörn , Messinger Paul 
Published: October 2006

AbstractCyclokondensation von γ‐Aryl‐γ‐oxosulfonen 1 mit 1,2‐ oder 1,3‐Diolen 2 und 3 führt zu 2‐Aryl‐2‐sulfonylethyl‐[1,3]‐dioxolanen 4 bzw. ‐dioxanen 5. Diese reagieren in Gegenwart von Kalium‐tert‐butylat unter Eliminierung von Sulfinsäure zu den Titelverbindungen 6 und 7.
The Structure—Activity Relationship of a New Anti‐Arrhythmic Agent 1‐[2‐Acetoxy‐3‐(4‐phenyl‐1‐piperazinyl)propyl]pyrrolidin‐2‐one
Authors: Malawska Barbara , Filipek Barbara , Stadnicka Katarzyna , Ciechanowicz‐Rutkowska Maria 
Published: October 2006

AbstractThis paper reports the synthesis of the new compound 1‐[2‐acetoxy‐3‐(4‐phenyl‐1‐piperazinyl)propyl]pyrrolidin‐2‐one (Ac‐MG‐1). Preliminary pharmacological assessment revealed that Ac‐MG‐1 possesses anti‐arrhythmic activity and a local anesthetic effect. The crystal structure of Ac‐MG‐1 was determined by X‐ray diffraction, and conformational analysis was performed both for Ac‐MG‐1 and for other derivatives of (arylpiperazinyl)propylpyrrolidin‐2‐one.
Antifungal Agents, Part 11: Biphenyl Analogues of Naftifine: Synthesis and Antifungal Activities
Authors: Porretta Giulio Cesare , Fioravanti Rossella , Biava Mariangela , Artico Marino , Villa Adelaide , Simonetti Nicola 
Published: October 2006

AbstractA series of naftifine analogues having the biphenyl instead of the naphthyl moiety have been synthesized in a search devoted to study bioanalogues of clinically efficacious antifungal agents. The new derivatives were tested against Candida albicans by the direct contact method. They were also assayed against Gram‐positive and Gram‐negative bacteria and against some isolates of plant pathogenic fungi. Derivatives 8a, 8c, and 9a were found to be active against Candida albicans, derivative 5a was active against E. coli, a very resistant species to antimycotic agents, and derivatives 8a and 8b inhibited the plant pathogenic Rhizoctonia solani.
4′,17‐Dioxo‐5′H‐estra‐1(10),4‐dieno[3,2‐b]furan: Synthesis, Binding Affinity to the Estrogen Receptor, Uterotrophic and Antiimplantation Activities
Authors: Omar A. Mohsen M. E. , Aboulwafa Omaima M. , Labouta Ibrahim M. , El‐tombary Alaa A. A. , El‐Mallah Ahmed I. 
Published: October 2006

Abstract4′,17‐Dioxo‐5′H‐estra‐1(10),4‐dieno[3,2‐b]furan (3) has been prepared by several routes starting from 2‐bromoacetylestrone (2). Performance of the reaction with thiourea at elevated temperature provided compound 3 in good yield. When other reagents such as thiosemicarbazide, morpholine, sodium hydroxide or sodium hydride were treated with 2‐bromoacetylestrone at room temperature, the furano derivative 3 was also obtained as the sole product. This new type of structural modification provided an estrogen nucleus deprived of the 3‐hydroxyl function which was previously thought to be an essential requisite for binding to the estrogen receptor (ER). When evaluated in vitro for binding to the ER and in vivo for uterotrophic and antifertility activities, the furano derivative 3 was capable of inhibiting[3H]E2 binding by 16% while still eliciting high uterotrophic (99%) and postcoital antimplantation (100%) activities relative to estradiol.
Analogues of Carbacholine: Synthesis and Relationship between Structure and Affinity for Muscarinic and Nicotinic Acetylcholine Receptors
Authors: Søkilde Birgitte , Mikkelsen Ivan , Stensbøl Tine B. , Andersen Birgit , Ebdrup Søren , Krogsgaard‐Larsen Povl , Falch Erik 
Published: October 2006

AbstractA series of acyclic and heterocyclic analogues of carbacholine (1) was synthesized using N‐methylcarbacholine (MCC, 2), N,N‐dimethylcarbacholine (DMCC, 3), and the corresponding tertiary amine (4) as leads. Whereas nicotinic acetylcholine receptor affinity was determined using [3H]nicotine as the radioactive ligand, [3H]oxotremorine‐M ([3H]Oxo‐M) and [3H]quinuclidinyl benzilate ([3H]QNB), in some cases supplemented with [3H]pirenzepine ([3H]PZ), were used as radioligands for muscarinic acetylcholine receptors on rat brain membranes. On the basis of receptor binding data, nicotinic/muscarinic (N/M) selectivity factors were determined, and muscarinic receptor efficacy (M agonist index) and M1 selectivity (M2/M1 index) estimated. In most cases, quaternized analogues showed higher affinity than the corresponding tertiary amines for muscarinic and, in particular, nicotinic receptor sites. Among the new compounds, N,N‐diethylcarbacholine (9e) (IC50 = 0.046 μM), (S)‐1‐methyl‐2‐(N,N‐diethyl‐aminocarbonyloxymethyl)pyrrolidine (17k) (IC50 = 0.068 μM), and the corresponding quaternized analogue, 18k (IC50 = 0.018 μM) showed the highest nicotinic receptor affinity. The tertiary amine, 17k showed much higher nicotinic receptor affinity than the acyclic analogue, 4 (IC50 = 5.7 μM), and the N/M selectivity factor determined for 17k (150) is an order of magnitude lower than that of nicotine (1400). The N/M selectivity factors for MCC (2) and DMCC (3), previously reported to be highly selective nicotinic receptor ligands, were shown to be 6.5 and 60, respectively, the latter value being comparable with that of 18k (89).
Proton NMR Conformational Analysis of Cyclic β‐Casomorphin Analogues of the Type Tyr‐cyclo[‐Nω‐D‐Orn‐Xaa‐Yaa‐Gly‐]
Authors: Mrestani‐Klaus Carmen , Brandt Wolfgang , Schmidt Ralf , Neubert Klaus , Schiller Peter W. 
Published: October 2006

AbstractA conformational study of the cyclic β‐casomorphin‐5 analogues H‐Tyr‐cyclo[‐D‐Orn‐2‐Nal‐Pro‐Gly‐] (1) (μ‐selective agonist; 2‐Nal = 2‐naphthylalanine), H‐Tyr‐cyclo[‐D‐Orn‐2‐Nal‐D‐Pro‐Gly‐] (2) (mixed μ agonist/δ antagonist) and H‐Tyr‐cyclo[‐D‐Orn‐Phe‐D‐Pro‐Gly‐] (3) (highly potent μ and δ agonist) has been carried out using 1H NMR spectroscopy. A complete assignment of the proton resonances of the three pentapeptides has been achieved. Compound 1 was shown to exist in two conformations, a major one (90%) characterized by a cis amide bond between 2‐Nal3 and Pro4, and a minor one (10%) showing cis amide bonds both between D‐Orn2 and 2‐Nal3 and between 2‐Nal3 and Pro4. Peptides 2 and 3 each showed only one conformer with all‐trans peptide bonds in both cases. Temperature dependence studies of the amide proton chemical shifts indicated the existence of several intramolecular hydrogen bonds in the case of compounds 2 and 3 but not in the case of peptide 1. The backbone conformations of 2 and 3 were found to be similar, both being characterized by two consecutive γ turns around the D‐Pro4 and D‐Orn2 residues, respectively, and by a D‐Orn2‐CO←HNδ‐D‐Orn2 hydrogen bond. Altogether, the overall backbone conformation and the preferred side chain conformation were found to be roughly similar for the three title peptides. For all three compounds a close proximity between the aromatic moiety of the 3‐position residue (2‐Nal or Phe) and the D(or L)‐Pro4 residue was established on the basis of ROESY experiments. The examination of low energy conformations obtained in molecular modelling studies by taking into account the various experimentally found NMR parameters (NOEs, vicinal H,H coupling constants, torsion angles, H‐bonds) led to proposals of the solution conformation for each peptide. These conformations are in close agreement with a pharmacophore model for μ opioid receptor binding compounds.
Comparative Conformational Analysis of CCK‐B Agonist Boc‐Trp‐Phg‐Asp‐(1‐Nal)‐NH2 and CCK‐B Antagonist Boc‐Trp‐Phg‐Asp‐(1‐Nal)‐N(Me)2 Using 1H NMR Spectroscopy and Restrained Molecular Dynamics
Authors: Goudreau Nathalie , Weng Juan Hui , Roques Bernard P. 
Published: October 2006

AbstractThe tetrapeptide Boc‐Trp‐Phg‐Asp‐(1‐Nal)‐NH2 is a potent CCK‐B agonist. Interestingly, bis‐methylation of the C‐terminal carboxamide group of this compound leads to Boc‐Trp‐Phg‐Asp‐(1‐Nal)‐N(Me)2 which behaves as a CCK‐B antagonist in electrophysiological studies on hippocampal neurones (Corringer et al., 1993). In order to ascertain whether bismethylation of the terminal carboxamide group has an influence on the conformational preferences of the peptide, we have undertaken a comparative conformational analysis of the two tetrapeptides by the combined use of 2D NMR spectroscopy and restrained molecular dynamics. The solution conformation of the two peptides was examined by 1H NMR in a d6‐DMSO/H2O (80:20) mixture. 1H‐1H distance constraints, derived from 2D NOESY and ROSEY experiments, were used as inputs for subsequent restrained molecular dynamics simulations. Comparison of the NMR and molecular modeling data indicates different conformational preferences for these two peptides. Interestingly, the aromatic side chains of the CCK‐B antagonist Boc‐Trp‐Phg‐Asp‐(1‐Nal)‐N(Me)2 in its preferential conformation, overlap their corresponding moieties in the two non peptide CCK‐B antagonists L‐362,260 and LY‐288,513. The differences in conformational behaviour of the studied tetrapeptides could, at least in part, account for their opposite agonist/antagonist profile, a findings which could serve for the design of new conformationally restricted CCK‐B analogs.
Hypolipidemic Activity of 3‐Amino‐1‐(2,3,4‐mononitro‐, mono‐, or dihalophenyl)propan‐1‐ones in Rodents
Authors: Huang Yunsheng , Hall Iris H. 
Published: October 2006

AbstractA series of 3‐amino‐1‐(2,3,4‐mononitro‐, mono‐, or dihalophenyl)propan‐1‐ones were synthesized and shown to be effective in lowering both serum cholesterol and triglyceride levels significantly in CF1 mice and Sprague‐Dawley rats. All analogs showed better activity than the standard drugs, lovastatin and clofibrate, in reducing the serum cholesterol and triglyceride levels in mice at 8 mg/kg/day intraperitoneally. The best active analogs, 3‐morpholino‐1‐(3‐nitrophenyl)propan‐1‐one (4) and 3‐piperidino‐1‐(3‐nitrophenyl)propan‐1‐one (5), exhibited 58% and 67% reduction of serum cholesterol levels, respectively, and 42% and 46% reduction of serum triglyceride levels, respectively, after 16 days of administration at 8 mg/kg/day intraperitoneally in CF1 mice. In Sprague‐Dawley rats at 8 mg/kg/day oral administration, both compounds (4 and 5) significantly decreased the serum cholesterol and triglyceride levels. Rat tissue lipid levels were reduced significantly by compound 4, while less effects resulted from compound 5. The cholesterol and triglyceride levels in chylomicrons, VLDL, and LDL fractions were reduced by both analogs while the HDL cholesterol levels were significantly increased. Compound 5 was also effective in lowering serum cholesterol and triglyceride levels in hyperlipidemic mice, at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day orally. Cholesterol and triglyceride lowering effects of the agents were correlated with inhibition of the activities of liver acetyl CoA synthetase, HMG CoA reductase, phosphatidylate phosphohydrolase, and lipoprotein lipase, and with elevation of the activity of cholesterol ester hydrolase.
Sulfogriseofulvin Derivatives. Synthesis by [4+2]Cycloaddition, Structure, Properties, Crystal Structure Analysis, and Antifungal Activity of Spiro[1,3‐benzoxathiole‐2,1′‐cyclohex‐2′‐en]‐4′‐one 3,3‐Dioxides
Authors: Friedrich Michael , Meichle Wilhelm , Bernhard Harald , Rihs Grety , Otto Hans‐Hartwig 
Published: October 2006

AbstractSyntheses of substituted, especially of fluoro substituted benzoxathiole 1,1‐dioxides, are described. These derivatives were transformed via the Peterson olefination into substituted 2‐alkylidene derivatives 27. Diels‐Alder reactions of 27 with 1,1‐dimethoxy‐ and 1‐methoxy‐3‐trimethylsiloxy‐1,3‐butadiene (30, 32) gave sulfone analogues 31 of griseofulvin (named sulfogriseofulvins). From Z‐27, a number of cis‐isomers with the relative stereochemistry of griseofulvin (cis‐31) was prepared, and from E‐isomers of 27, compounds (trans‐31) with relative stereochemistry of epigriseofulvin were obtained. Some related compounds (33, 38) are synthesized by slight modifications. The stereochemistry is established by spectroscopic methods and crystal structure analyses. The compounds 31 were tested against three species of dermatophytes. The biological activities were all significantly lower than that of griseofulvin.
Scavenging of Free Radicals by Tenoxicam: A Participating Mechanism in the Antirheumatic/Antiinflammatory Efficacy of the Drug
Authors: Facino Roberto Maffei , Carini Marina , Saibene Luisella 
Published: October 2006

AbstractThe radical scavenging activity of tenoxicam against hydroxyl (HO⋅), superoxide (O2⋅−), and peroxyl (LOO⋅) radicals, all of them involved in the inflammatory reactions, has been tested in different cell‐free systems and by different techniques. Tenoxicam is a good scavenger of both HO⋅ radicals (IC50 = 56.7 μM), as determined by Electron Spin Resonance (ESR) spectroscopy with the spin trapping (5,5‐dimethyl‐1‐pyrroline N‐oxide, DMPO) technique, and O2⋅− radicals generated by the phenazine methosulfate/reduced β‐nicotinamide adenine dinucleotide (PMS/NADH) system. The high reactivity of the drug towards HO⋅ was confirmed by the rate constant of reaction with HO⋅ (k ⋍ 1010 M−1s−1), determined by competition kinetic studies with N,N‐dimethyl‐4‐nitrosoaniline. In addition at a μM level (1–5 μM) it dose‐dependently prevents the phycoerythrin peroxidation induced by the water‐soluble azoinitiator 2,2‐azobis(2‐amidinopropane) dihydrochloride (ABAP), indicating a quenching effect on aqueous peroxyl radicals. The HO⋅‐entrapping capacity was confirmed in models more close to the in vivo situation: tenoxicam inhibits the HO⋅‐induced depolymerization of hyaluronic acid already at 15 μM and the HO⋅‐driven lipid peroxidation in phosphatidylcholine liposomes (PCL) with an IC50 of 10 μM. In this membrane model it delays at 1–10 μM level the decomposition of phosphatidylcholine hydroperoxides to short‐chain alkenals (markers: total carbonyl functions as 2,4‐dinitrophenylhydrazones and conjugated dienes). The high susceptibility of the drug of HO⋅ attack is also demonstrated by its extensive degradation (HPLC studies) when irradiated with HO⋅ radicals. The antioxidant component of tenoxicam evidenced in this study sheds some light on the hitherto undefined mechanism of the antiinflammatory action of the drug.
Synthesis of 6‐ and 9‐Ethylocatadecanoic Acids
Authors: Dragas Dario , Tanojo Hanafi , Brussee Johannes , Junginger Hans E. , Boddé Harry E. 
Published: October 2006

AbstractSpecific branched fatty acids are of great interest in the search of a new type of drug penetration enhancers across human skin for transdermal drug delivery and in gaining an understanding of structure‐activity relationships with skin lipids. A convenient synthesis has therefore been developed especially for ethyloctadecanoic acids. The successful syntheses of 6‐ and 9‐ethyloctadecanoic acids are reported here.
Synthesis and Antitumour Activity of New Derivatives of Flavone‐8‐acetic Acid (FAA). Part 1: 6‐Methyl Derivatives
Authors: Aitkena R. Alan , Bibby Michael C. , Double John A. , Phillips Roger M. , Sharma Shiv Kumar 
Published: October 2006

AbstractA range of 17 derivatives of flavone‐8‐acetic acid (FAA) with a 6‐methyl substituent have been prepared and their anti‐tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.