bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentiell ZNS‐Wirksame, tricyclische Verbindungen mit verbrücktem Mittelring, 5. Mitt.1): Synthese von 9‐substituierten 9,10‐Epithio‐9,10‐dihydroanthracenen
Authors: Linde Hermann F. G. , Krämer Norbert H.
Published: October 2006

Es werden zwei Synthesewege vorgestellt, die ausgehend von Benzo[c]thiophen‐1‐carbonsäuremethylester (1) zu 9‐substituierten 9,10‐Epithioanthracenderivaten führen:

Diels‐Alder‐Reaktion von 1 mit 1,4‐Benzochinon gibt das mit Schwefel überbrückte Ringsysteme 2.

Wird in Benzo[c]thiophenderivate überführt, die eine stickstoffhaltige Seitenkette besitzen, z.B. 11, 12. Anellierung eines weiteren Ringes mit 1,4‐Benzochinon führt unter H2S‐Eliminierung zu den 1,4‐Dioxoanthracenderivaten 13a und 13b. Die 9,10‐Epithio‐9,10‐dihydroanthracenverbindung 14 wird nur als Nebenprodukt isoliert. Als Ursache der Instabilität der Diels‐Alder‐Produkte sehen wir ihre Oxidationsempfindlichkeit gegenüber 1,4‐Benzochinon an.
Antineoplastika, 17. Mitt.1): Darstellung mono‐ und disubstituierter 2,4‐Dichlor‐6‐diethylamino‐1,3,5‐triazine
Authors: Kreutzberger Alfred , Langner Peter , Stratmann Jörg
Published: October 2006

Die Umsetzung von 2,4‐Dichlor‐6‐diethylamino‐1,3,5‐triazin (1) mit den sekundären Aminen 2a‐g führt zu den Diamino‐1,3,5‐triazinen 3a‐g und den Melaminen 4a und 4b. Die Struktur der Endprodukte wird durch die IR‐, 1H‐NMR‐ und Massenspektren charakterisiert.
5‐Acyloxydioxolanone als Prodrugs nichtsteroidaler Antirheumatika, 1. Mitt.
Authors: Schwenker Gerhard , Stiefvater Karlheinz
Published: October 2006

Die Derivatisierung verschiedener saurer nichtsteroidaler Antirheumatika zu 5‐Acyloxy‐1,3‐dioxolan‐4‐onen wird beschrieben. Die Synthese der Titelverbindungen gelingt durch Umsetzung von 5‐Brom‐1,3‐dioxolan‐4‐onen mit den Carbonsäuresalzen.
Substituierende Ringspaltung von 2‐Phenyl‐3,5,6,7,8,8a‐hexahydro‐imidazo[1,2a]pyridin‐1‐oxid
Authors: Möhrle Hans , Gehlen Michael
Published: October 2006

Das cyclische α‐Aminonitron 2 ergibt bei Umsetzung mit Grignard‐Reagenzien nicht, wie früher vermutet, substituierte Hydroxylamine vom Typ 4, sondern unter Ringspaltung 2‐substituierte Piperidinoxime 7 und 8, deren Struktur durch unabhängige Synthese bewiesen wurde. Durch HPLC‐Analyse konnte gesichert werden, daß die Ringöffnung unter Konfigurationserhalt der Nitronstruktur zum E‐Oxim verläuft.
Sukzessive Ringmethylierung von α‐Piperidino‐oximen durch wiederholte Zwei‐Stufen‐Reaktion
Authors: Möhrle Hans , Gehlen Michael
Published: October 2006

Durch Dehydrierung von α‐Piperidino‐acetophenonoximen mit Hg(II)‐ED‐TA und konsekutive Grignard‐Reaktion gelingt die stufenweise Ringmethylierung des Piperidin‐Cyclus unter Konfigurationserhalt sowohl bei den E‐als auch den Z‐konfigurierten Isomeren. Die Ringverknüpfung der bicyclischen Oxidationsprodukte läßt sich anhand der 13C‐NMR‐Daten ermitteln.
Further Characterization of the Solid Forms of Iopanoic Acid and its Enantiomers
Authors: Pitrè Davide , Amici Marco De , Colombo Mario , Gualberto Gallo Gian , Nebuloni Marino
Published: October 2006

The enantiomers of iopanoic acid were purified by crystallization and characterized by optical rotation, DSC, IR spectra, X‐ray powder diffraction, and chiral HPLC. (‐R)‐enantiomer: [α]20D = −6.1°, mp. = 165.4°C; (+S)‐enantiomer: [α]20D = + 6.2°, mp. = 165.6°C. The IR spectra and X‐ray patterns are fingerprints. Chiral HPLC (isocratic method, mobile phase: ethanol/n‐hexane, 2/98 with 0.5% acetic acid) gave a resolution = 0.98 and a 99.6% recovery.

From X‐ray and thermal analyses the racemate Form I, mp. = 153.8°C, resulted to be a racemic compound. The binary phase diagram between the enantiomers and the racemic compound was constructed from the phase transition temp. obtained by DSC heating curves of appropriate mixtures. At a given enantiomer ratio (71/29) a eutectic compound, mp. = 144.7°C, is formed. In the range 88–100% a solid solution between the components is observed.
Synthese von 1,2‐Thiazinen und 1,2‐Thiazepinen durch Ringerweiterung
Authors: Stachel Hans‐Dietrich , Poschenrie Hermann , Lomitzky Viktor
Published: October 2006

Die β‐Ketosultame 3 und 11 werden durch Aldolkondensation zu den entspr. Alkylidenderivaten 4, 5 bzw. 12 umgesetzt. Epoxidation von 5 und 12 führt zu den Epoxyketonen 6 und 13, die mit Bortrifluorid‐Etherat zum 1,2‐Thiazin 7 bzw. zum 1,2‐Thiazepin 14 isomerisieren.
Synthesis and Antiprotozoal Properties of 1,2,6‐Thiadiazine 1,1‐Dioxide Derivatives
Authors: Herrero Angela , Ochoa Carmen , Atienza Juan , Escario J. Antonio , Gómez‐Barrio Alicia , Mart Femández Antonio R. Índez
Published: October 2006

The synthesis and spectroscopical data of 1,2,6‐thiadiazine 1,1‐dioxides, designed as antiprotozoal agents, are reported. The in vitro trichomonacidal and trypanocidal activities of new compounds and their precursors were evaluated against Trichomonas vaginalis and Trypanosoma cruzi. The chemoprophylactic activity on mice treated with blood infected with T. cruzi and their mortality percentage were tested. Compounds 2 and 8b show a higher chemoprophylactic activity and lower mortality percentage than Nifurtimox used as reference drug.
Synthese enantiomerenreiner 6,10‐Epoxybenzocycloocten‐7‐amine mit ZNS‐Aktivität
Authors: Wünsch Bernhard , Zott Matthias , Höfner Georg
Published: October 2006

In einer oxa‐analogen Pictet‐Spengler‐Reaktion kondensiert der (S)‐Phenylmilchsäureester 6 mit Methyllävulinat (7a) zu den 2‐Benzopyranen cis‐8a und trans‐8a, die sich mit CH3I zu den Dimethylethern cis‐9a und trans‐9a alkylieren lassen. Durch Mitteldruck‐Flüssigchromatographie lassen sich die Diastereomeren cis‐9a und trans‐9a trennen. Bei der anschließenden Dieckmann‐Cyclisierung liefert cis‐9a direkt den linksdrehenden β‐Ketoester (‐)‐10a, während trans‐9a erst nach Epimerisierung an C‐3 zum rechtsdrehenden Enantiomer (+)‐10a cyclisieren kann. Die Enantiomerenreinheit des Ketons (‐)‐11, das durch Verseifen und Decarboxylieren des β‐Ketoester (‐)‐10a zugänglich ist, wird mit Eu(hfc)3 überprüft. Durch reduktive Aminierung von (‐)‐11 lassen sich die Amine (‐)‐12a und (‐)‐12b gewinnen, die nach i. p. Applikation bei Mäusen Symptome hervorrufen, die für zentrale Dämpfung sprechen. Im Writhing‐Test der Maus wird für (‐)‐12a HCl ein ED50‐Wert (7.0 mg/kg) gefunden, der in der Größenordnung des ED50‐Wertes von Tramadol liegt.
Thion‐ und Dithioester, 52. Mitt.: Zur Reaktion von Dithionmalonestern mit N,N‐Dimethylformamidacetalen
Authors: Hartke Klaus , Kraska Andreas
Published: October 2006

Bei der Reaktion der Dithionmalonester 1 mit den Formamidacetalen 2 entsteht ein Gemisch der 2‐(Dialkylaminomethylen)dithionmalonester 4 und der Thionacrylester 6. Die Kondensation von 4 mit Hydrazinen liefert die Pyrazole 7 und 8, mit Hydroxylaminsulfonsäure die Isothiazole 10 und mit Amidinen die Pyrimidine 11‐13.
Benzomorphan‐Analoga mit Doxpicomin Partialstruktur: Synthese und psychopharmakologische Untersuchung von 5‐Aminomethyl und 5‐(α‐Aminobenzyl) substituierten 2,6‐Epoxy‐3‐benzoxocinen
Authors: Wünsch Bernhard , Bauschke Gerd
Published: October 2006

Addition des β‐Alanin‐Derivats 6 an das Homophthalaldehydmonoacetal 5 und anschließende LiAlH4‐Reduktion führten zu dem Dihydroxyacetal 8, das sich mit Säure zu den 5‐Aminomethyl‐2,6‐epoxy‐3‐benzoxocinen 2a und 2b cyclisieren ließ. Die Umsetzung von 5 mit dem Anion des β‐Lactams 9 lieferte zwei trennbare Diastereomere: 10a mit u,l‐Konfiguration und 10b mit 1,1‐Konfiguration. Das β‐Lactam‐Addukt 10a (10b) wurde über das 2‐Benzopyran 11a (11b), den Aminoalkohol 12a (12b) und das sekundäre Amin 13a (13b) in das 5‐(α‐Dimethylaminobenzyl)‐2,6‐epoxy‐3‐benzoxocin 3d (3b) überführt. Die relativen Konfigurationen aller Produkte dieser „β‐Lactam‐Route”︁ (10‐13, 3d und 3b) wurden durch Auswertung der 1H‐NMR‐Spektren aufgeklärt. Versuche, die noch fehlenden Diastereomere 3a und 3c durch Epimerisierung der β‐Lactame 11a und 11b oder durch reduktive Aminierung der Benzoyl‐Derivate 17a und 17b zu gewinnen, mißlangen. 3a und 3c wurden schließlich durch Phenylmagnesiumbromid‐Addition an die Nitrile 21a und 21b, gefolgt von LiAlH4‐Reduktion, Formaldehyd/NaBH3CN‐Methylierung und chromatographischer Trennung erhalten. ‐ Im Irwin‐Screen (Maus) zeigten nur 2a · HCl, 3b und 3d bei einer Dosis von 100 mg/kg Körpergewicht schwache ZNS‐Effekte.
Mammary Tumor Inhibiting [1,2‐Bis(2,6‐dihalo‐3‐hydroxyphenyl)ethylenediamine]platinum(II) Complexes, III: Relationship between Structure and Estrogenic Activity of the Diamine Ligands, their Sulfatoplatinum (II) and Diiodoplatinum(II) Complexes
Authors: Gust Ronald , Schönenberger Helmut
Published: October 2006

1,2‐Bis(2,6‐dihalo‐3‐hydroxyphenyl)ethylenediamines with 2,6‐Cl2, 2‐F,6‐Cl, 2‐Cl,6‐F, and 2,6‐F2 substituents (meso‐1 to meso‐4, D.L‐1 and D.L‐4) and their sulfatoplatinum(II) complexes were tested in the immature mouse uterine weight test. The only complex with marked estrogenic properties proved to be meso‐1‐PtSO4. Surprisingly its diamine ligand meso‐1 was only marginally active. 1H‐NMR spectroscopic studies on the 1,2‐diphenylethylenediamine ligand reveal that the 2,6‐standing Cl‐atoms in meso‐1 (antiperiplanar phenyl residues) hinder the rotation of the aromatic rings, which results in very stable conformers with different O‐O distances owing to the unsymmetric arrangement of the ring substituents. On transformation into the Pt(II) complex the conformations of meso‐1 change (synclinal phenyl residues) and a δ and λ interconversion takes place already at physiological temp. (37°C). This process is accompanied by a rotation of phenyl rings, which is supposed to allow an optimal fit for the formation of hydrogen bridges to the estrogen receptor, resulting in a marked estrogenic activity. The other ligands and complexes are inactive presumably due to a diminished hydrophobic interaction with the estrogen receptor, resulting from their R,R/S,S‐configuration or the reduced number of Cl‐atoms.
Synthesis and Chemotactic Activity of the fMLP Analog HCO‐Hmb‐Leu‐Phe‐OMe
Authors: Zecchini Giampiero Pagani , Paradisi Mario Paglialunga , Torrini Ines , Lucente Gino , Traniello Serena , Spisani Susanna
Published: October 2006

The new fMLP analog HCO‐Hmb‐Leu‐Phe‐OMe (1), containing (S)‐2‐hydroxy‐4‐(methylthio)butyric acid (Hmb) in place of L‐methionine at the N‐terminal position, has been synthesized and fully characterized. The peptide 1 has been designed in order to improve the understanding of the role exerted by the formamido group in the binding interaction with the formylpeptide chemotactic receptors. Chemotaxis, superoxide anion production, and lysozyme release have been measured for both 1 and its deformylated analog Hmb‐Leu‐Phe‐OMe 2. Results indicate that a strong hydrogen bond of the OH·…OC type may complement a weak H‐bonding interaction involving the formylic proton as H‐bond donor.
Phenytoin‐Lipid Conjugates as Potential Prodrugs of Phenytoin
Authors: Scriba Gerhard K. E.
Published: October 2006

Phenytoin‐1‐triglycerides and phenytoin‐2‐triglycerides were synthesized as potential prodrugs of phenytoin by covalent binding of 3‐hydroxymethylphenytoin by succinic acid to the positions 1 and 2 of diglycerides, respectively. The corresponding 1‐ and 2‐monoglycerides were prepared. In addition, replacement of glycerol by 3‐hydroxy‐2‐hydroxymethylpropionic acid furnished lipids that allowed direct coupling of 3‐hydroxyme‐thylphenytoin. The lipid conjugates proved to be substrates for pancreatic lipase in vitro.
New NO‐Donors with Antithrombotic and Vasodilating Activities, I: 3‐Arylalkyl‐N‐nitroso‐5‐sydnone Imines
Authors: Rehse Klaus , Kämpfe Michael , Schleifer Klaus‐Jürgen
Published: October 2006

Nine nitrosimino title compounds were prepared. They inhibit the aggregation of human platelets induced by collagen with an IC50 = 0.7 ‐ 33 μmol/L. The most active substance is the 3‐phenylethyl derivative 6b. The in vitro effect is mediated by an active metabolite which is formed by a photochemical reaction in the aggregometer. As the corresponding and so far unknown sydnone‐5‐cyanimines have no effect on platelets the metabolite is most certainly a NO‐species. The activity of the sydnone‐5‐nitrimine 5b is in the same order of magnitude (IC50 = 7.5 μmol/L) as in the nitrosimines of type 6. The most active compound 6b was investigated for antithrombotic properties in a thrombosis model, where the thrombus formation was induced by a laserbeam. 2 h after oral administration of 60 mg/kg of 6b to rats in venoles a 28% inhibition of thrombin formation was found. In arterioles this effect is more evident and a 48% inhibition is seen (the thrombus formation index is 2.6 and 3.9, respectively). These results suggest that the active metabolite is formed as well in vivo.
Indole, 9. Mitt.: 4‐Arylierte Tetrahydro‐β‐carboline ‐ Synthesewege und erste pharmakologische Daten
Authors: Lehmann Jochen , Jiang Naicai , Behncke Andreas
Published: October 2006

Zwei verschiedenen Wege führen zu den 4‐arylierten Tetrahydro‐β‐carbolinen 5, 11 und 12. Der eine beinhaltet einen Pictet‐Spengler‐Ringschluß der Tryptamine 9, der andere folgt unserem „Lactonweg”︁2), beginnend mit 1 über 2‐4. In ersten pharmakologischen Tests der Zielverbindungen wurde signifikante Affinität am 5‐HT2‐Rezeptor, dagegen keine oder nur geringe Affinität zu verschiedenen anderen Bindungsstellen gefunden.
Synthese homochiraler 5,9‐Epoxybenzocyclooctene mit Aminsubstituenten: Zusammenhang zwischen Struktur und ZNS‐Aktivität
Authors: Wünsch Bernhard , Zott Matthias , Höfner Georg
Published: October 2006

Wir berichten über Synthese und psychopharmakologische Eigenschaften von Variationen der sedierend und analgetisch wirksamen tricyclischen Amine 3a und 3b: Ausgehend von dem homochiralen Keton 4 werden die Amine 5 (primäre Aminogruppe in äquatorialer Position), 7 (axial angeordnete Dimethylaminogruppe), 9 (zusätzlicher Phenylring in 7‐Stellung), 13b und 14b (äquatorial bzw. axial stehende Dimethylaminomethylgruppe) und 23 und 24 (in 9‐Position verschobene, axial ständige Aminogruppe) dargestellt. BBr3 spaltet die beiden Phenolether des sekundären Amins (±)‐3a zu dem Aminodiphenol (±)‐10. Die Beobachtung von Mäusen auf Verhaltensanomalien (Irwin‐Screen) und analgetische Wirksamkeit (Writhing Test) zeigt, daß die Amine 5, 7, 9, (±)‐10, 13b, 14b und 23 die sedativen und analgetischen Effekte der von uns bereits beschriebenen Amine 3a und 3b nicht erreichen.
Synthesis of Potential Impurities of Cefalexin and Cefradine
Authors: Hendrix Christel , Roets Eugène , Bervoets Valère , Thomas Josiane , Pijcke Martine , Busson Roger , Janssen Gerard , Hoogmartens Jos
Published: October 2006

The synthesis of some impurities of the cephalosporin antibiotics cefalexin and cefradine is described. These impurities which may be present in commercial samples are formed during the semi‐synthetic preparation of these antibiotics or upon their degradation. The preparation of these compounds enables the validation of selective quantitative analytical methods, such as column liquid chromatography and thin layer chromatography.
1,5‐Benzodiazepine, 2. Mitt.: Entgegengesetzte zentralnervöse Wirkungen der Enantiomere von zwei 3,3‐Dialkyl‐1,5‐benzodiazepin‐2,4‐dionen
Authors: Knabe Joachim , Büch Horst Paul , Bender Susanne
Published: October 2006

Nach i.p.‐Applikation (50–200 mg) an Ratten zeigten rac. 1, S(+)‐1 und R(−)‐1 nur eine schwach ausgeprägte dosisunabhängige Verlängerung der Hexobarbitalschlafzeit ohne enantioselektive Wirkungsunterschiede. Rac. 3 verlängerte die Hexobarbitalschlafzeit überhaupt nicht. Die Untersuchung der Gewebeverteilung und der Konzentration im Serum ergab, daß 1 und 3 nach i.p.‐Applikation im Serum und Gehirn zwar nachweisbar, aber nicht quantifizierbar waren. Nach i.v. Applikation erwiesen sich die S(+)‐Enantiomere von 1 und 3 überraschenderweise als konvulsiv wirksam. Sie sind in der Wirkungsintensität dem Pentetrazol um den Faktor 2.5‐5 überlegen. R(−)‐1 und R(−)‐3 verlängerten dagegen nach i.v. Gabe die Hexobarbitalschlafzeit, und zwar R(−)‐1 dosisabhängig. Die durch S(+)‐1 ausgelösten Krämpfe wurden durch Vorbehandlung mit Diazepam unterdrückt, nicht aber durch Flumazenil. Die Enantiomere R(−)‐1 und R(−)‐3 sind schwache Agonisten, S(+)‐1 undS(+)‐3 offensichtlich starke inverse Agonisten. Enantioselektive Unterschiede traten auch bei der Bindung der 1‐Enantiomere an Humanserumalbumin auf: R(−)‐1 wurde stärker gebunden als S(+)‐1.
α‐Thiotetronsäuren, 1. Mitt.: Synthese und Eigenschaften von γ‐Alkyliden‐α‐thiotetronsäuren
Authors: Stachel Hans‐Dietrich , Zeitler Klaus
Published: October 2006

Es wird über die Synthese der Alkyliden‐α‐thiotetronsäuren 11 und 12a und mehrere ihrer Derivate berichtet. Ausgangsverbindungen sind das 2,3‐Dimethoxybernsteinsäure‐thioanhydrid (4) sowie Thioacetondicarbonsäureester. Bei der Rhodium(II)‐katalysierten Zersetzung des Diazoketons 26 entsteht das Redukton 12p und das Aminoredukton 12r. Eines der Nebenprodukte ist das Thietanon 27.
Synthesis and Biological Investigations of Some New Thiazolylbenzimidazoles and Benzimidazolylthiazolo[3,2‐a]pyridines
Authors: Rida S. M. , Habib N. S. , Badawey E. A. M. , Fahmy H. T. Y. , Ghozlan H. A.
Published: October 2006

2‐[(4‐Oxo‐4,5‐dihydrothiazol‐2‐yl)methyl]‐1H‐benzimidazole (2) was prepared through the reaction of 2‐cyanomethyl‐1H‐benzimidazole (1) with thioglycolic acid. The syntheses of its arylidene 3 and diazo‐coupled compounds 5 and the cyclization of the aforementioned thiazolylbenzimidazole to benzimidazolylthiazolo[3,2‐a]pyridines 8 were also performed. The prepared compounds were screened for their in‐vitro antibacterial, antifungal, anti‐HIV, and anticancer activities: they show promising antifungal activity.
Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XXIX: Influence of the Antithrombotic Oligoamine RE 1492 on the Storage of Red Blood Cells, Morphology, their Potassium and ATP Content, Hemolysis and Viability
Authors: Rehse Klaus , Müller Susann
Published: October 2006

The influence of RE 1492 on the storage of red blood cells (RBCs) was investigated. RE 1492 (c ⩾ 50 μmol/L) induces the formation of cup cells and hence delays the appearance of echinocytes and crenated spheres in the blood. A concentration of 50 μmol/L RE 1492 drops hemolysis by 50 %. At this concentration after 6 h of storage the potassium efflux was enhanced significantly. The ATP concentration was decreased between 12 h and 24 h of storage. During the first 6 h these alterations have no effect on the in vivo viability of RBCs. After 12 h of storage a significant reduction in viability is observed. We suppose that the changes observed are due to the intercalation of RE 1492 in the phospholipid matrix of the RBC membrane, followed by an accelerated substrate turnover in the RBCs.
Preparation and In Vitro Pharmacology of 5‐HT4 Receptor Ligands. Partial Agonism and Antagonism of Metoclopramide Analogous Benzoic Esters
Authors: Elz Sigurd , Keller Andreas
Published: October 2006

Alicyclic ester analogues of the gastroprokinetic benzamide metoclopramide (1) and its ester congener SDZ 205557 (2), a 5‐HT4 receptor antagonist, were prepared by O‐alkylation of 4‐amino‐5‐chloro‐2‐methoxybenzoate with N‐(2‐chloroethyl) substituted alicyclic amines. The bromo and iodo analogue of compound 13b (2‐(1‐piperidinyl)ethyl 4‐amino‐5‐chloro‐2‐methoxybenzoate) were obtained by halogenation of dechloro‐13b with N‐halogenated succinimides. The series was evaluated in functional in vitro assays with regard to affinity for serotoninergic 5‐HT4, 5‐HT3 and muscarinic M3 receptors. The affinities for 5‐HT4 and M3 receptors were below 6.0 (pKB or pA2). On 5‐HT4 receptors in guinea‐pig ileal longitudinal muscle and rat oesophagus, the majority of compounds revealed partial 5‐HT4 receptor agonism susceptible to blockade by SDZ 205557, a reference 5‐HT4 receptor antagonist (pKb = 7.25 − 7.73 (guinea‐pig ileum) and 7.09 — 7.43 (rat oesophagus)). The relative agonist potency was in the range of 5 – 303 % (5‐HT: 100 %). Compound 13b and its bromo analogue 17 were the most potent esters of the series. The enantiomers of 13g ((R)‐ and (S)‐2‐(2‐methyl‐1‐piperidinyl)ethyl 4‐amino‐5‐chloro‐2‐methoxybenzoate) interacted stereoselectively with 5‐HT4 receptors and displayed enantiomeric potency ratios (R)/(S) of 4.3 — 8.7. There was an excellent correlation between (a) antagonist affinity on guinea‐pig ileum and rat oesophagus, (b) relative agonist potency on guinea‐pig ileum and rat oesophagus, and (c) between antagonist affinity and relative agonist potency within each assay (r2 > 0.91). The new compounds may serve as academic tools in evaluating the functional role of 5‐HT4 receptors. The selective partial 5‐HT4 receptor agonists presented in this paper may be useful to restore physiological motility and secretion in the gut with reduced or absent propensity to elicit tachycardia and desensitization of the intestinal target receptor.
Synthesis of GABA‐Valproic Acid Derivatives and Evaluation of Their Anticonvulsant and Antioxidant Activity
Authors: Rekatas George V. , Tani Ekaterini , Demopoulos Vassilis J. , Kourounakis Panos N.
Published: October 2006

The synthesis and the anticonvulsant activity of a number of GABA and valproic acid derivatives are reported. The lipophilicity of these compounds and their inhibitory effect on lipid peroxidation were also investigated, in an effort to correlate the anticonvulsant activity with lipophilicity and inhibitory effect on lipid peroxidation. The synthesized compounds exhibited anticonvulsant effects which were stronger for the more lipophilic derivatives. One of the active anticonvulsants showed appreciable antioxidant properties. Finally, a good correlation was found between the experimentally derived (RM) and calculated (σ and log PSK) lipophilicity for this series of compounds.
Aminoalcohols Related to Tramadol (Tramal®)
Authors: Horstmann Petra , Unterhalt Bernard
Published: October 2006

Aminoalcohols related to the opioid tramadol (1) were synthesised. Their binding capacities to subtypes of the opioid receptor were tested.
Passive Kühlung und sommerliche Überhitzung – Sind Simulationen auf der Grundlage des Test Reference Year (TRY) ein geeignetes Bewertungskriterium?
Authors: Rozynski Matthias
Published: October 2006

Die beobachteten Klimaänderungen führen zu einer Häufung warmer Sommer. Die sechs heißesten wurden in den letzten neun Jahren seit Beginn der Gebietsmittelzeitreihe – d. h. beginnend mit dem Jahr 1901 – gemessen, die Spitze bildet dabei der Rekordsommer 2003. Deshalb stellt sich die Frage, mit welchen Maßnahmen hohe Raumtemperaturen in Verwaltungsgebäuden, insbesondere im Sanierungsfall, wirksam verhindert werden können.
„Und setzet eure Worte nicht auf Schrauben”︁ Medizinische Semiotik vom Ende des 18. bis zum Beginn des 20. Jahrhunderts ‐ Gegenstand und Forschung
Authors: Eckart Wolfgang U.
Published: October 2006

There is no doubt that medical semiotics are having a revival at the moment. Different aspects of yesterday's and today's interest in semiotics and in the historical interpretation of signs of disease in the context of theory and history of medicine can be illuminated: their deciphering as the history of the sign in medicine by historic science, their overestimation by philosophy during the Age of Enlightenment, their reduction to a phenomenology of medicine and natural science during the first half of the 19th century and their transformation to medical diagnostics since the middle of the 19th century and recently even their functionalization as methodical instrument within the history of science. The following will show the change in meaning of medical semiotics. Modern development and especially the transition to medicine, based on natural science, will be emphasized.
Alchemie als Nichtchemie zu Beginn der Neuzeit
Authors: Schütt Hans‐Werner
Published: October 2006

In this paper certain aspects of alchemy are discussed in the light of corresponding aspects in chemistry. The paper also attempts to give some reasons for the upsurge of alchemy in early Modern Times.
Wie Huren und Betrüger — die Begegnung des jungen Descartes mit der Welt der Praktiker der Mathematik
Authors: Schneider Ivo
Published: October 2006

Descartes describes in the Discours de la méthode his stay in Germany in winter 1619/20 as decisive for his intellectual development. In Germany he was especially interested in the mathematics of German reckoningmasters and mathematical practitioners. Frustrated from their form of representation, from their mathematical „style”︁, he began to create his own, which he considered a first step in the development of his method in order to secure true knowledge. Descartes could derive additional confirmation for his task by the mentalities of orthodox and heterodox protestantism. He learned that Johannes Faulhaber one of the leading German mathematicians had strong connections to the rosicrucian movement, a very popular form of heterodox protestantism. The convictions and aims of the supporters of the rosicrucian movement in part agreed with and in part contradicted seriously those of Descartes, whereas the arguments of the orthodox protestants in their fight against the rosicrucian movement interacted positively with the ideas of Descartes. The reaction of Descartes to his encounter with German protestantism offers an important element for the explanation of the strong positive and negative reactions to Cartesianism in protestant countries, especially in the Netherlands.
Lebens‐Geschichte ‐ Wissenschafts‐Geschichte. Vom Nutzen der Biographie für Geschichtswissenschaft und Wissenschaftsgeschichte
Authors: Szöllösi‐Janze Margit
Published: October 2006

Biography as a genre of historiography had been dismissed for some years, criticized for being conservative, resistant to theoretical approaches, and hostile to methodological innovations. But the predominance of a historiography devoted to structures, functions, and statistics has, however, led to a renewed interest in the human factor in history. This paper argues that the pluralism of methods and theories which has emerged thereafter reopened the case for an innovative biography, thus facilitating the convergence of general history and the history of science.
Wissenschaft im Gehäuse: Vom Nutzen und Nachteil institutionengeschichtlicher Perspektiven
Authors: vom Bruch Rüdiger
Published: October 2006

Research is realized in social and cultural context, it is established in institutions, as far as different forms and conditions of practice are concerned. In this article some German examples demonstrate how flexible and varied the institutions of research can be during the course of history of science. The first part deals with historically grown, yet chronologically overlapping institutions of research: beginning with the lonely scholar, going on to hierarchally organized big science and ending up with virtual institutions. In the second part, at the intersection of political‐social administration and styles of scientific thought terms like German Realpolitik, science in context, and science policy are discussed within the modernization process.
Raum und Disziplin. Klinische Wissenschaft im Krankenhaus
Authors: Hess Volker
Published: October 2006

The historical shift in the function of the hospital from an asylum for the care of the indigent sick to a medical‐therapeutic institution is intimately associated with the exploitation of the hospital as a clinical facility. Thus, over the course of the 19th century the space of the hospital and its disciplinary structure was permeated and reorganized by clinical practices.

Drawing on the example of the Charite hospital in Berlin, it can be shown how the historical shift in the hospital's outward social function went hand in hand with the creation of a differentiated internal clinical space. In this compartmentalized clinical space the discipline of the hospital was replaced with methods of clinical examination, techniques of observation, and procedures of documentation, all of which helped to transform the hospital into a knowledge‐space.
Aspekte zur Sammlungs‐ und Einrichtungsgeschichte des Berliner Pergamonmuseums
Authors: Matthes Olaf
Published: October 2006

This article focuses on the development of the Pergamon‐Museum of Berlin and its various collections. The predecessor of the current museum building gave only place for the Great Altar of Pergamon and some other architectural pieces of the hellenistic period. After its abolishment in 1908 the new erected building (which opened only in 1930) contained before World War II three museum departments (Deutsches Museum, Pergamon‐Museum, and the Vorderasiatisches Museum). ‐ There were some long‐lasting frictions between the directors Wilhelm von Bode, Theodor Wiegand, and the architect Ludwig Hoffmann about the question whether roman provincial architecture is worth to be exhibited in a museum or not ‐ here exemplified on the Market Gate of Miletus. Wilhelm II, the Kaiser, was strongly involved not only in this but was generally interested in all museum matters. It was always he who made the last decision, and the museum directors tried very often to persuade him of their ideas.
Hypercross‐Linked Fiber and its Adsorption of Cyclohexane Vapor
Authors: Yanli Z. , Li D. G. , Jiang D. G.
Published: October 2006

A novel hypercross‐linked fiber which has an excellent adsorption capacity for cyclohexane vapor was prepared by cross‐linking PP‐ST‐DVB fibers with p‐xylylenedichloride according to the Friedel‐Crafts reaction. The effects of several important factors on the Friedel‐Crafts reaction, including reaction temperature, reaction time, catalyst type, and material ratio were investigated in detail and the optimal synthesis conditions of hypercross‐linked fiber were obtained. The adsorption equilibrium for cyclohexane vapor on hypercross‐linked fiber was measured by a static volumetric technique. The equilibrium measurements were performed at 298, 323 and 348 K and pressures of up to 6.04 kPa. The results can be well fitted by the Freundlich model. The isosteric heat curve was derived from the equilibrium data, and indicates that the hypercross‐linked fiber has an energetically heterogeneous surface.
Donor/Conductor/Acceptor Triads Spatially Organized on the Micrometer‐Length Scale: An Alternative Approach to Photovoltaic Cells
Authors: Llabrés i Xamena Francesc X. , Teruel Laura , Alvaro Mercedes , Garcia Hermenegildo
Published: October 2006

We have used porous anodised Al2O3 membranes as inert matrix for constructing and organizing spatially ternary donor/conductor/acceptor (DCA) systems exhibiting photovoltaic cell activity on the micrometric‐length scale. These DCA triads were built stepwise by first growing a conducting polymer inside the membrane pores, thus forming nanorods that completely fill the internal pore space of the membrane. Then, an electron donor and an electron acceptor were adsorbed one on each side of the membrane, so that they were separated by a distance equal to the membrane thickness (ca. 60 μm), but electronically connected through the conductive polymer. When this device was placed between two electrodes and irradiated with visible light, electrons jumped from the donor molecule, crossed the membrane from side to side through the conductive polymer (a journey of about 60 μm!) until they finally reach the acceptor molecule. In so doing, an electric voltage was generated between the two electrodes, capable of maintaining an electric current flow from the membrane to an external circuit. Our DCA device constitutes the proof of a novel concept of photovoltaic cells, since it is based on the spatial organization at the micrometric scale of complementary, but not covalently linked, electron‐donor and electron‐acceptor organic species. Thus, our cell is based in translating photoinduced electron transfer between donors and acceptors, which is known to occur at the molecular nanometric scale, to the micrometric range in a spatially organised system. In addition our cell does not need the use of liquid electrolytes in order to operate, which is one of the main drawbacks in dye‐sensitised solar cells.
Palladium‐Catalyzed Intramolecular C(sp3)H Functionalization: Catalyst Development and Synthetic Applications
Authors: Hitce Julien , Retailleau Pascal , Baudoin Olivier
Published: October 2006

A novel catalytic system, based on a mixture of palladium acetate and tris(5‐fluoro‐2‐methylphenyl)phosphane (F‐TOTP), has been designed for the intramolecular CH functionalization of alkane segments. Among other analogues of tris(2‐methylphenyl)phosphane (P(o‐tol)3), F‐TOTP was shown to have the optimal metal‐bonding properties for this reaction. This catalytic system operated under milder reaction conditions that allowed the regioselective production of various olefins adjacent to a quaternary benzylic carbon atom, as well as novel bi‐ and tricyclic molecules. A general mechanism was proposed, with the preferential formation of a six‐membered palladium(II) palladacycle after oxidative addition and cyclopalladation. The regioselective CH functionalization of alkyl groups into olefins was illustrated in the synthesis of the antihypertensive drug verapamil (14) and an analogue (19). A particularly mild ruthenium‐catalyzed direct hydroamidation of the intermediate olefin in this synthesis is also reported.
Synthesis, Structures, and Properties of meso‐Phosphorylporphyrins: Self‐Organization through P–Oxo–Zinc Coordination
Authors: Matano Yoshihiro , Matsumoto Kazuaki , Terasaka Yukiko , Hotta Hiroki , Araki Yasuyuki , Ito Osamu , Shiro Motoo , Sasamori Takahiro , Tokitoh Norihiro , Imahori Hiroshi
Published: October 2006

The synthesis, structures, and optical and electrochemical properties of meso‐phosphorylporphyrins are described. The copper‐catalyzed carbon–phosphorus cross‐coupling reaction of a meso‐iodoporphyrin with di‐n‐butyl phosphite and diphenylphosphane oxide has proved to be an efficient and general method for the synthesis of meso‐phosphorylporphyrins. Zinc phosphorylporphyrins thus obtained readily undergo self‐organization through P–oxo–Zn coordination to form noncovalently linked, cofacial porphyrin dimers or linear oligomers, which have been characterized by spectroscopic methods and X‐ray crystallographic analyses. In toluene, CH2Cl2, and CHCl3, the zinc phosphorylporphyrins exist mostly as dimers or monomers, depending on their concentrations, the temperature, and the presence of additives. The self‐association constants for dimerization in toluene have been determined by UV/Vis absorption titration measurements. The meso‐diphenylphosphorylporphyrin dimer displays excitonic coupling of the Soret band with a splitting energy of 940 cm−1. Fluorescence lifetimes of the zinc phosphorylporphyrins have been found to be affected only slightly by the concentration of the solution, and by the addition of triphenylphosphane oxide, suggesting that the effect of dimerization on their photodynamics in the S1 state is negligible. On the other hand, the effect of dimerization is clearly reflected in their electrochemical oxidation processes, as the initially produced radical cations are efficiently delocalized over the two porphyrin rings. These findings demonstrate the potential utility of meso‐phosphorylporphyrins as new models for the special pair in photosynthesis and as new building blocks for porphyrin‐based supramolecular materials.
Semiclassical determination of exponentially small intermode transitions for 1 + 1 spacetime scattering systems
Authors: Joye Alain , Marx Magali
Published: October 2006

We consider the semiclassical limit of systems of autonomous PDEs in 1 + 1 spacetime dimensions in a scattering regime. We assume the matrix‐valued coefficients are analytic in the space variable, and we further suppose that the corresponding dispersion relation admits real‐valued modes only with one‐dimensional polarization subspaces. Hence a BKW‐type analysis of the solutions is possible. We typically consider time‐dependent solutions to the PDE that are carried asymptotically in the past and as x → −∞ along one mode only and determine the piece of the solution that is carried for x → +∞ along some other mode in the future. Because of the assumed nondegeneracy of the modes, such transitions between modes are exponentially small in the semiclassical parameter; this is an expression of the Landau‐Zener mechanism. We completely elucidate the spacetime properties of the leading term of this exponentially small wave, when the semiclassical parameter is small, for large values of x and t, when some avoided crossing of finite width takes place between the involved modes. © 2006 Wiley Periodicals, Inc.
Studies of Molybdenum Disulfide Nanostructures Prepared by AACVD Using Single‐Source Precursors
Authors: Adeogun A. , Afzaal M. , O'Brien P.
Published: October 2006

Nanostructures of hexagonal MoS2 thin films synthesized using air‐stable, single‐source molecular precursors of molybdenum dithiocarbamates are reported. On increasing the length of the substituent alkyl groups of the precursor, changes in the type of structures grown under similar growth conditions can be observed (see figure, scales 50 nm).
Bauaufsichtliche Einführung der DIN 1053‐100
Authors: Jäger Wolfram
Published: October 2006

Seit August 2006 liegt die DIN 1053‐100 nach dem neuen Teilsicherheitskonzept in konsolidierter Fassung vor. Die Norm ist in die Musterliste der Technischen Baubestimmungen aufgenommen worden und kann nunmehr in den Bundesländern eingeführt werden. Die lange Phase von der Veröffentlichung bis zur Einführung ist begründet in einer gewissen Schlechterstellung der Nachweise für horizontale Einwirkungen, in den Verschärfungen durch die neuen Lastnormen sowie durch die Erdbebennorm und in einem Defizit in der “heißen” Bemessung (Feuerwiderstand). Ersteres wurde versucht abzudämpfen. Für den Nachweis der Feuerwiderstandsdauer konnten leider noch keine Gewinne, die sich bei vertikaler Belastung ergeben, nutzbar gemacht werden. Jedoch ist es gelungen, eine klare Lösung zu finden.

Es ist nunmehr eine durchgängige Bemessung und Nachweisführung für Gebäude nach dem Teilsicherheitskonzept möglich. Der Beitrag gibt Hintergrundinformationen zu den Änderungen und Hinweise zur Anwendung der DIN 1053‐100.
Neuroblastoma tumors with favorable and unfavorable outcomes: Significant differences in mRNA expression of genes mapped at 1p36.2
Authors: Fransson Susanne , Martinsson Tommy , Ejeskär Katarina
Published: October 2006

The distal part of 1p is frequently deleted in aggressive neuroblastoma, and the region is believed to harbor one or more tumor suppressor genes relevant to tumor development. To analyze differences among neuroblastoma tumors, an expression profile was established for the genes mapped within a previously described shortest region of overlap of deletions at 1p36.2. The gene expression levels were quantified by TaqMan real‐time (RT)‐PCR for 30 transcripts using 55 primary neuroblastoma tumors. Here we report on a significant decrease in gene expression of the genes RERE, PIK3CD, LZIC, PGD, and PEX14 and an increase of SLC2A5 when comparing tumors of favorable biology to Stage 4 neuroblastomas. When comparing 1p‐deleted tumors of all stages to tumors with an intact 1p, a significant difference at gene‐by‐gene level in TNFRSF9, RERE, PIK3CD, CLSTN1, CTNNBIP1, and CASZ1 was detected. A complete loss of expression could not be seen for any single gene analyzed. Several of the genes with diminished expression in unfavorable or 1p‐deleted tumors have functions that could contribute to tumor development. It is also possible that a combination of lowly expressed genes at 1p, rather than one single classical tumor suppressor gene, causes the unfavorable outcome associated with 1p‐deletion in neuroblastoma. © 2006 Wiley‐Liss, Inc.
Overlay analysis of the oligonucleotide array gene expression profiles and copy number abnormalities as determined by array comparative genomic hybridization in medulloblastomas
Authors: Lo Ken C. , Rossi Michael R. , Burkhardt Tania , Pomeroy Scott L. , Cowell John K.
Published: October 2006

Combined analysis of gene expression array data and array‐based comparative genomic hybridization data have been used in a series of 26 pediatric brain tumors to define up‐ and downregulated genes that coincide with losses, gains, and amplifications involving specific chromosome regions. Frequent losses were defined in chromosome arms 3q, 6q, 8p, 10q, 16q, 17p, and gains were identified in chromosome 7, and chromosome arms 9p and 17q. Amplification of a 2p region was seen in only one tumor, which corresponded to increased expression of the MYCN and DDX1 genes. To facilitate the analysis of the two data sets, we have developed a custom overlay tool that defines genes that are underexpressed in regions of deletions and overexpressed in regions of gain, across the genome and specifically within regions showing recurrent involvement in medulloblastomas. © 2006 Wiley‐Liss, Inc.
High score on the Relative Stress Scale, a marker of possible psychiatric disorder in family carers of patients with dementia
Authors: Ulstein Ingun , Wyller Torgeir Bruun , Engedal Knut
Published: October 2006

Objective

To compare the scores on the Relative Stress Scale (RSS) with those on the General Health Questionnaire (GHQ) and the Geriatric Depression Scale (GDS), and to establish a cut‐off score for RSS in order to distinguish carers with symptoms of psychiatric disorders from those without.

Methods

One hundred and ninety‐four carers of 194 patients suffering from dementia according to ICD‐10 were included in the study. Burden of care was assessed by the 15‐items RSS, and psychiatric symptoms by means of the GHQ‐30 and the 30‐items GDS. A case score above 5 on GHQ and above 13 on GDS were used to define carers with probable psychiatric morbidity. Sensitivity (SS), specificity (SP), accuracy and likelihood ratio for a positive test (LR+) were calculated for different cut‐points of the RSS.

Results

Fifty‐six percent of the carers had a GHQ score above 5, and 22% had a GDS score above 13. A two‐step cluster analysis using 192 of the 194 carers, identified three groups of carers; a low risk group for psychiatric morbidity (LRG), 82 carers with GHQ ≤ 5 and GDS ≤ 13; a medium risk group (MRG), 69 carers with GHQ > 5 and GDS ≤ 13; and a high‐risk group (HRG), 40 carers with GHQ > 5 and GDS > 13. The optimal RSS cut‐off to distinguish between the LRG and the others was > 23 (SS 0.72, SP 0.82, accuracy 0.76, LR + 4.0), whereas the optimal cut‐off to separate the HRG from the others was >30 (SS 0.74, SP 0.87, accuracy 0.84, LR + 5.7).

Conclusion

The RSS is a useful instrument to stratify carers according to their risk of psychiatric morbidity. Copyright © 2006 John Wiley & Sons, Ltd.
Different structural components of conventional papillary thyroid carcinoma display mostly identical BRAF status
Authors: Abrosimov Alexander , Saenko Vladimir , Rogounovitch Tatiana , Namba Hiroyuki , Lushnikov Evgeny , Mitsutake Norisato , Yamashita Shunichi
Published: October 2006

Activating BRAFT1799A mutation is closely associated with a papillary thyroid carcinoma (PTC) histotype. The transversion is frequently detected in the conventional type, Warthin‐like and tall cell variants, but is rare in the follicular variant of PTC. Conventional PTC is often presented with tumors of mixed architecture, which besides the papillary structures also contain areas with follicular and solid morphology in which the details of BRAF mutational status are unknown. We set out to differentially investigate the presence of mutated BRAF in the individual structural components microdissected from 44 formalin‐fixed, paraffin‐embedded PTC tissues from 40 patients. The mutation was detected in at least 1 structural component in 23 tumors (52%). Different structural components of the same tumor had identical BRAF status in 41/44 tumors (93%). In 3 tumors the BRAFT1799A mutation was found only in the papillary, but not in the follicular component. Mutational patterns identical to those in the primary tumors were found in 11/12 lymph node metastases (92%, including both BRAFT1799A‐positive and ‐negative cases). The high concordance of the BRAF mutational status in structurally distinct areas suggests a rather homogeneous distribution of neoplastic epithelial cells in a conventional PTC tumor in most cases. These results imply the reliability of preoperative molecular diagnosis of PTC regardless of the type of tumor component at the site of biopsy sampling and suggest that the majority of patients with BRAF mutation‐positive PTC may benefit from the targeted pharmacotherapy. © 2006 Wiley‐Liss, Inc.
Hemodynamic and calorimetric changes induced by microcystin‐lr in the rat
Authors: Leclaire Ross D. , Parker Gerald W. , Franz David R.
Published: October 2006

Microcystin‐LR, a cyclic peptide from the cyanobacterium Microcystis aeruginosa, given at acutely toxic doses causes severe hepatic interstitial hemorrhage. Hemodynamic, calorimetric and acid–base balance changes after i.v. microcystin were measured. The effect of isoproterenol, dopamine, methylprednisolone and whole‐blood volume expansion on the immediate hemodynamic effects after toxin administration were also evaluated. A dose of 100 μg kg−1 was invariably lethal for rats in all studies. Pathophysiological changes included: a sustained, rapid decline in cardiac output and stroke volume; an acute hypotension responsive to volume expansion with whole blood; a decreased heart rate, responsive to both isoproterenol and dopamine; an early decline in oxygen consumption, carbon dioxide production and metabolic rate accompanied by progressive hypothermia; and acid–base balance changes indicating partially compensated metabolic acidosis. The lethal effects of microcystin‐LR were previously attributed to hypovolemic shock as a result of hepatic interstitial hemorrhage. These results indicate that, in addition, there may be a cardiogenic component that limits the physiological cardiac reserve, compromising a normal response to circulatory inadequacy.
Mechanism of testicular atrophy induced by di‐n‐butyl phthalate in rats. Part 5. Testicular iron depletion and levels of ferritin, haemoglobin and transferrin in the bone marrow, liver and spleen
Authors: Fukuoka Masamichi , Kobayashi Tetsu , Hayakawa Takao
Published: October 2006

This study reports changes in levels of ferritin, haemoglobin and transferrin in the bone marrow, liver and spleen as an attempt to determine the causes of testicular iron depletion. A single oral dose of di‐n‐butyl phthalate (DBP) to male rats caused a sloughing of the germ cells (at 6 h) prior to testicular atrophy. Before the sloughing it was observed that DBP induced decreases both in the iron levels in the blood, bone marrow and testis and in haemoglobin (Hb) levels in the blood, bone marrow and spleen. Decrease in transferrin (Tf) levels was observed in the liver. Significant increases in ferritin and haemosiderin (Hs) levels were observed in the spleen and in the liver and spleen, respectively.

In vitro studies where mono‐n‐butyl phthalate (MBP) was incubated with liver homogenates, MBP caused both the decreases in Hb and Tf‐bound iron levels and increases in Hs and Hs–iron levels.

The present study proposes that the mechanism of testicular atrophy by DBP might be associated with both the iron release from Hb and/or Tf in the liver and spleen and the subsequent depletion of iron in the blood and testes.