bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthese und Antitumorwirkung von Iso‐Piritrexim, einem lipophilen Folatantagonisten
Authors: Troschütz Reinhard , Zink Mario , Dennstedt Thomas 
Published: October 2006

AbstractEs werden zwei Synthesewege von Iso‐Piritrexim (12) beschrieben. A) Die Aminomethylierung des Ketons 2 ergibt die Mannich‐Basen 4‐HCI und 5‐HCI, von denen 4, nach sc‐Abtrennung, mit in situ erzeugtem 3,3‐Diaminoacrylnitril (9) zum 2‐Aminonicotinsäurenitril 11 cyslisiert. Der Ringschluß von 11 mit Guanidin führt zum Iso‐PTX(12). B) Durch Reduktion und Oxidation des β‐Ketoesters 15 gelangt man zu einem β‐Keto‐aldehyd 17, der mit 2,4,6‐Triaminopyrimidin (18) zu Iso‐PTX (12) cyclokondensiert. Iso‐PTX (12) zeigte im Antitumortest des NCl eine mittlere Aktivität gegenüber einigen Leukämie‐ und Lungenkrebszellinien.
Synthesis and Evaluation of Azole‐Substituted Tetrahydronaphthalenes as Inhibitors of P450 arom, P450 17, and P450 TxA2
Authors: Hartmann Rolf W. , Frotscher Martin , Ledergerber Dorothea , Wächter Gerald A. , Grün Gertrud L. , Sergejew Tom F. 
Published: October 2006

AbstractIn search of potential drugs for the treatment of estrogen‐ and androgen‐dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol‐4‐yl, imidazol‐1‐yl, or 1,2,4‐triazol‐1‐yl substituent in 2‐position were synthesized with and without C1‐spacer between the rings (compounds 2 – 26). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin‐primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene‐induced tumor; pre‐ and postmenopausal model).In the series of imidazol‐4‐yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7‐OCH3‐2‐(imidazol‐4‐ylmethylene)‐1‐tetralone (4) and 7‐OCH3‐2‐(imidazol‐4‐ylmethyl)‐tetralin (12) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12, the 6‐OCH3 derivative (compound 11) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol‐1‐yl compounds show a marked inhibition of P450 TxA2: 2‐(imidazol‐1‐ylmethyl)‐1‐tetralone (13) is a selective inhibitor of P450 TxA2, whereas 7‐OCH3‐2‐(imidazol‐1‐ylmethyl)‐tetralin (17) as well as 2‐(imidazol‐1‐ylmethyl)‐tetralin (16) and 7‐OCH3‐2‐imidazol‐1‐yl‐3,4‐dihydronaphthalene (25) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests.
On the Concept of a Bivalent Pharmacophore for SKCa Channel Blockers: Synthesis, Pharmacological Testing, and Radioligand Binding Studies on Mono‐, Bis‐, and Tris‐quinolinium Compounds
Authors: Galanakis Dimitrios , Ganellin C. Robin , Dunn Philip M. , Jenkinson Donald H. 
Published: October 2006

AbstractThe dissociation equilibrium constants (Kd values) of dequalinium (2) and the monoquinolinium compounds 1a and 1b have been determined from competition equilibrium radioligand binding with [125I]apamin on rat brain synaptic plasma membranes (SPMs). Dequalinium binds to the channel with 2 orders of magnitude higher affinity than 1a or 1b, suggesting that both quinolinium groups are needed for potent and selective SKCa channel blockade. The trisquinolinium compound 3 (1,1′‐[5‐[4‐(4‐aminoquinolinium‐1‐yl)but‐1‐yl] non‐4‐en‐1,9‐diyl]‐bis‐(4‐aminoquinolinium)) has been synthesized and tested for inhibition of the afterhyperpolarization of rat sympathetic neurones and on the binding assay. Compound 3 shows approximately one order of magnitude higher potency than 2, being the most potent non‐peptidic SKCa channel blocker reported so far (Kd ∽ 30 nM). The higher affinity of 3 compared with 2 may be due to direct binding of the third quinolinium group to the channel or may arise from a reduction of the unfavorable entropy of binding via an increase of the „local concentration”︁ of quinolinium groups.
3‐Hydroxymethylphenytoin Valproic Acid Ester, a New Prodrug Combining Two Anticonvulsant Drugs
Authors: Scriba Gerhard K. E. 
Published: October 2006

Abstract3‐Hydroxymethylphenytoin valproic acid ester (VAL‐PHT) was designed as a new prodrug combining valproic acid and phenytoin, two anticonvulsant drugs with different pharmacological profiles. The compound was hydrolyzed by rat plasma esterases in vitro but exhibited only activity in the maximal electroshock seizure test (MES test) after intraperitoneal administration to mice. The compound did not protect against pentylenetetrazole‐induced seizures. It is concluded that VAL‐PHT acts as a prodrug displaying the anticonvulsant profile of phenytoin.
N‐ω‐Carbethoxypentyl‐4‐quinolones: A New Class of Leukotriene Biosynthesis Inhibitors
Authors: Desideri Nicoletta , Sestili Isabella , Stein Maria Luisa , Manarini Stefano , Dell'Elba Giuseppe , Cerletti Chiara 
Published: October 2006

Abstract6‐[(4‐Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B4 and thromboxane B2 production. While all 6‐[(4‐quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N‐alkyl‐4‐quinolones, obtained as by‐products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.
Structure‐Activity Relationships of Sandalwood Odorants: Synthesis and Odour of Methyl‐β‐santalol
Authors: Buchbauer Gerhard , Zcchmeister‐Machhart Friederike , Weiß‐Greilar Petra , Wolschann Peter 
Published: October 2006

AbstractThe synthesis and odour properties of the new santalol analogue, methyl‐β‐santalol, are described. The additional methyl group adjacent to the hydroxyl function of the standard molecule, β‐santalol, deprives the new compound of the sandalwood note. The synthesis and the odour evaluation of this compound supports the proposed model for sandalwood fragrance as it shows that the methyl group located at the osmophoric center prevents association of the molecule with the hypothetical receptor.
Structure‐Activity Relationship Studies of CNS Agents, Part 32[1]: Effect of Structural Modifications in 1‐Arylpiperazine Derivatives on α1‐Adrenoreceptor Affinity
Authors: Mokrosz Maria J. , Paluchowska Maria H. , Charakchieva‐Minol Sijka , Bień Anna 
Published: October 2006

AbstractThe α1‐adrenergic and 5‐HT1A serotonergic receptor affinities of a series of 1‐arylpiperazines are presented. The role of the spacer and the influence of the terminal substituents on the α1‐adrenoreceptor affinity and the 5‐HT1A/α1 receptor selectivity are discussed.
Aza‐Analogs of 8‐Styrylxanthines as A2A‐Adenosine Receptor Antagonists
Authors: Müller Christa E. , Sauer Roland , Geis Uli , Frobenius Wolfram , Talik Przemyslaw , Pawlowski Maciej 
Published: October 2006

AbstractIn the present study we synthesized aza‐analogs of 8‐styrylxanthines, in which the ethenyl bridge is replaced by an imine, amide, or azo function, in order to investigate structure‐activity relationships of the 8‐substituent of A2A‐selective xanthine derivatives. Thus, various 8‐substituents were combined with theophylline or caffeine, respectively, and affinities of the novel compounds for adenosine A1‐ and A2A‐receptors were determined and compared with those of analogous 8‐styrylxanthine derivatives. 8‐(Benzylideneamino)caffeine derivatives exhibited high affinity and selectivity for A2A‐adenosine receptors, but were unstable in aqueous buffer solution at physiological pH values. 8‐(Phenylazo)caffeine derivatives were less potent than corresponding 8‐styrylcaffeine derivatives at adenosine receptors. The most potent azo compound of the present series was 8‐(m‐chlorophenylazo)caffeine (14b) exhibiting a Ki value of 400 nM at A2A‐adenosine receptors and 20‐fold selectivity versus A1‐receptors. Due to the facile synthetic access to 8‐(phenylazo)xanthine derivatives, which are obtained by coupling of 8‐unsubstituted xanthines with phenyldiazonium salts, 14b may be an interesting new lead compound for the development of more potent and selective A2A‐antagonists with azo structure.
Synthesis of Vinca Alkaloids and Related Compounds. Part 84. Sulfonamide Derivatives of Some Vinca Alkaloids with Cardiovascular Activity
Authors: Moldvai István , Temesvári‐Major Eszter , Szántay Csaba , Tóth Gábor , Kárpáti Egon , Szántay Csaba 
Published: October 2006

Abstract(+)−Vincamine (1) and (+)−vinpocetine (2) were chlorosulfonylated and the resulting sulfonyl chloride isomers (3–6) were transformed into sulfonamides (7–10). The ester group of sulfonamides was modified by selective hydrolysis and transesterification. Apovincaminol derivatives (14–16) were also prepared by reduction. In addition to the known cerebrovascular effects of the unsubstituted compounds (1,2), sulfonamides also show a significant peripheral vasodilator effect.
Synthesis of N‐Aryl‐N′‐heteroaryl‐Substituted Urea and Thiourea Derivatives and Evaluation of Their Anticonvulsant Activity
Authors: Heinisch Gottfried , Matuszczak Barbara , Rakowitz Dietmar , Tantisira Boonyong 
Published: October 2006

AbstractStarting from amino(di)azines and 2‐chloro‐6‐methyliso(thio)cyanate a series of aryl‐substituted urea and thiourea derivatives was prepared and screened as potential antiepileptics. Among the new derivatives tested, only 2b and 3c exhibited adequate anticonvulsant effects, whereas 3d and 4d were found to be convulsants per se.
Synthesis and Bone Resorption Effect of Alkoxy‐Substituted Xanthones
Authors: Pifferi Giorgio , Re Paolo Da , Valenti Piero , Bisi Alessandra , Malandrino Salvatore 
Published: October 2006

AbstractA topological modification of ipriflavone 1, a recent antiosteoporotic drug, is described. The flavone moiety of 1 has been replaced by a xanthone one. Among the new derivatives, the 3,6‐diisopropoxyxanthone (2a) has shown significant bone resorption inhibition in in vitro and in vivo tests.
Chemical and Biological Properties of 5‐Indolones
Authors: Weber Wolfgang , Habermann Anne , Maisch Caren Claudia , Eger Kurt 
Published: October 2006

AbstractIndolones of the general formula 1 (Fig. 1 and 2) can act as Michael substrates, which readily add various nucleophiles. 1,4‐Addition of S‐nucleophiles to these indolones gives access to compounds of the general formula 2 (Fig. 2). The addition is reversible, meaning that these compounds behave as prodrugs of the (in‐vitro) cyto‐toxic indolones. The addition products possess less cytotoxicity of their own, but can presumably release the parent indolones in‐vivo. This behaviour makes them valuable compounds, allowing their use as cytotoxic agents. Furthermore, some of the addition products possess antibiotic activity, making them worth testing as agents against certain microbes. Their specificity towards certain microorganisms, which does not fit the usual scheme of activity towards gram positive or gram negative bacteria, is remarkable and needs further verification.
Organic Nitrates II[1]. Synthesis and Biological Activities of 4‐Nitrooxymethylphenyl‐1,4‐dihydropyridines
Authors: Lehmann Jochen , Kahlich Rainer , Gottesberge Christoph Meyer Zum , Fricke Uwe 
Published: October 2006

AbstractBoth 2‐nitrooxymethyl‐4‐phenyl‐ (2) and 4‐nitrooxymethylphenyl‐1,4‐dihydropyridines (3) represent new combinations of two different vasodilating structures. 2 could not be isolated due to its spontaneous lactonization. Derivatives of 3 were obtained via Hantzsch synthesis using nitrooxymethylated benzaldehydes. The inotropic potency in isolated porcine trabecular muscles and the vasodilator activity in isolated porcine coronary arteries of four nitrooxyphenyl‐dihydropyridines were determined. Nitrendipine (NTD) and glyceryl trinitrate (GTN) were used for reference. 3 were negative inotropic, however, less than NTD and ‐ except for the dicyano derivative 3d ‐ more than GTN. Vasodilator properties were less pronounced than that of both nitrendipine and GTN. Vascular selectivity was low.
Synthesis and Antibacterial Activities of New 1β‐Methylcarbapenems Having a 1,3‐Diazabicyclo[3.3.0]octan‐2,4‐dione Moiety
Authors: Nam Ki‐Hong , Oh Chang‐Hyun , Ham Young‐Wan , Lee Ki‐Soo , Cho Jung‐Hyuck 
Published: October 2006

AbstractThe synthesis of a new series of 1β‐methylcarbapenems having a 1,3‐diazabicyclo[3.3.0]octane‐2,4‐dione moiety is described. Their in vitro antibacterial activities against both Gram‐positive and Gram‐negative bateria are determined and the effect of substituent on the bicyclic ring as well as stereoisomerism was investigated.
Studies on Propafenone‐type Modulators of Multidrug‐Resistance IV: Synthesis and Pharmacological Activity of 5‐Hydroxy and 5‐Benzyloxy Derivatives
Authors: Chiba Peter , Tell Barbara , Jäger Walter , Richter Elisabeth , Hitzlera Manuela , Ecker Gerhard 
Published: October 2006

AbstractA series of 5‐hydroxy and 5‐benzyloxy analogs of the antiarrhythmic and multidrug resistance (MDR) modulating drug propafenone was synthesized and the MDR‐modulating activity of the compounds was evaluated using a daunomycin efflux assay system. The key step of the synthesis is the selective reduction of the double bond in 1 without cleavage of the benzyl group thus leading to the phenol 3. Alkylation with epichlorohydrine followed by nucleophilic epoxide ring opening gave the benzylated target compounds 5a–d. Subsequent cleavage of the benzyl group gave the 5‐hydroxy analogs 6a–d. Structure activity relationship studies showed, that the 5‐hydroxy derivates 6a–d fit the log P/log potency correlation line previously established for a series of propafenone analogs. In contrast, all four 5‐benzyloxy analogs 5a–d showed almost identical EC50 values, independent of their log P value.
2‐Amino‐2‐Oxazolines, Part VIII. Calculated Molecular Properties of Tautomeric Species
Authors: Ouhabi Jamal , Jarry Christian , Zouanate Abdelhadi , Carpy Alain 
Published: October 2006

AbstractThe geometries, tautomerization energies, and dipole moments of the tautomeric species of the 2‐amino‐2‐oxazoline heterocycle were calculated with full geometry optimization using semiempirical (MNDO, AM1 and PM3) and ab initio (RHF/6–31G) methods. The planar conformation of the amino form is well reproduced by the semiempirical and by the ab initio methods as compared with X‐ray structures in which this form is found. However the exocyclic nitrogen atom is pyramidalized in the semiempirical geometries whereas the ab initio method reproduces a sp2 hybridization state. The twisted conformation of the imino form is better reproduced by the ab initio calculation. All methods (semiempirical and ab initio) show a stability energy value in favour of the amino tautomer of the neutral heterocycle. On the contrary, the dominant species of the charged heterocycle is the imino tautomer, protonated on the exocyclic nitrogen atom. Molecular electrostatic potential calculations confirmed this tendency. Finally the 3D‐lipophilicity profile of the heterocycle completed the investigation of the tautomerism.
2‐Substituted Naphthazarins; Synthesis and Antitumor Activity
Authors: Kyong‐Up Baik , Yong Song Gyu , Yong Kim , Dai‐Eun Sok , Byung‐Zun Ahn 
Published: October 2006

AbstractA series of 2‐substituted naphthazarin derivatives, 5,8‐dihydroxy‐1,4‐naphthoquinone (DHNQ) derivatives and 5,8‐dimethoxy‐1,4‐naphthoquinone (DMNQ) derivatives, were synthesized, and their cytotoxic activity against some cancer cell lines and antitumor action against S‐180 tumor were evaluated. In general, 2‐(1‐hydroxyalkyl)‐DHNQ derivatives showed a higher cytotoxicity than 2‐(1‐hydroxyalkyl)‐DMNQ derivatives, implying a predominent role of redox cycling rather than electrophilicity in cytotoxicity. 2‐(1‐Alkoxy‐4‐methylpentyl) or 2‐(1‐acyloxy‐4‐methylpentyl) derivatives were produced by alkylation or acylation at the C‐1′ position of 2‐(1‐hydroxy‐4‐methylpentyl)‐DHNQ or DMNQ derivatives. Although the cytotoxicity differed according to the size of the alkyl or acyl chain, alkylation or acylation at the C‐1′ position did not improve the cytotoxicity remarkably, and DHNQ derivatives were still more cytotoxic than DMNQ derivatives. Separately, in vivo testing showed that 2‐(1‐acyloxyalkyl)‐DHNQ derivatives or 2‐(1‐alkoxyalkyl)‐DHNQ derivatives expressed a higher antitumor action than 2‐(1‐hydroxyalkyl)‐DMNQ or ‐DHNQ derivatives in contrast to the cytotoxicity observations. The total size of two side chains at C‐1′ seemed to govern the antitumor activity, with 9 to 11 carbon atoms being optimal. Thus, it is suggested that the physical properties as well as the chemical reactivity are to be considered in relation to the antitumor action of 2‐substituted naphthazarin compounds.
Why Science May Serve Political Ends: Cultural Imperialism and the Mission to Civilize
Authors: Pyenson Lewis 
Published: October 2006

AbstractZusammenfassung: Der Beitrag beginnt mit einem wissenschaftssoziologischen Diskurs, der sich der generellen Frage nach Zusammenhängen zwischen großen gesellschaftlichen und politisch‐ideologischen Strömungen auf der einen Seite sowie intellektuellen Innovationen und den Wissenschaften auf der anderen Seite widmet. Problemfelder wie „class and education”︁ und deren Interdependenz mit den klassischen von Max Weber geprägten Beeinflussungskräften jeder entwickelten Zivilisation werden berührt. Gegenüber den deskriptiven „Baconian sciences”︁ scheinen die exakten Wissenschaften am wenigsten offenkundig ideologisch beeinflußt oder beeinflußbar.Von diesem Eindruck ausgehend widmet sich der Beitrag der Frage, ob ein solches Vorurteil haltbar sein kann, und kommt dann zu der weitergehenden Frage, wie die exakten Wissenschaften durch den westlichen Imperialismus geformt werden konnten und wurden. Hauptsächliches Untersuchungsobjekt des Verfassers ist die französische Überseephysik der zwanziger und dreißiger Jahre dieses Jahrhunderts insbesondere in Algier und Shanghai. Als Kristallisationskerne der Darstellung dienen die Biographien von Jean Coulomb (Algier) und Pierre Lejay (Shanghai). Darüber hinaus werden exemplarisch Zusammenhänge zwischen den exakten Wissenschaften und dem Versuch Frankreichs herausgearbeitet, an seiner imperialen Peripherie Kultur‐ bzw. Zivilisationsmission zu betreiben. Der Verfasser umreißt mit seiner Fragestellung nach der Rolle der exakten Wissenschaften im Zusammenhang mit der französischen Kulturmission in Nordafrika und in Ostasien zugleich die Geschichte eines letztlich gescheiterten ideellen Projektes. Durch den engen Konnex zwischen Wissenschaftlern an der kulturkolonialen Peripherie und dem Wissenschaftsmanagement in der Kolonialmetropole Paris wurden nämlich sowohl die kritische Reflexion über die metropolitane Physik als auch deren kreative Umsetzung und Ausweitung an der Peripherie verhindert.
Kulturimperialismus und Kulturwissenschaften
Authors: Vom Bruch Rüdiger 
Published: October 2006

AbstractAround 1900 in the Second German Empire the industrial society transformed to an imperialistic society. Before that public discussion dealt with the social integration of the working classes into the nation, whereas after 1900 the point of public interest expanded to cultural topics in general. For the future formation of nation and society seemed undecided; there was a thorough discussion about the identity and the chances of development of a political culture. This forms the background for a dispute within the humanities about the unity of the historische Kulturwissenschaften (Max Weber) and for the struggle of the historian Karl Lamprecht for a foreign cultural policy of the Reich under the leadership of the humanities on the Eve of World War I.
British Influence on Australian Physics, 1788–1988
Authors: Jenkin John G. 
Published: October 2006

AbstractThe influence of the traditions, methodologies and practices of British physics on Australian physics has been extraordinarily strong, from the earliest days of the colony (when astronomy and meteorology were of some interest) until very recent times (when other influences, particularly from the USA, have become apparent). In Australia's second century of European settlement, the influence of the Cavendish Laboratory at Cambridge University has been especially important. These influences have been outlined, and their effects on Australian physics have been discussed.
Die Medizin und das „Größere Deutschland”︁: Kolonialpolitik und Tropenmedizin in Deutschland, 1884–1914
Authors: Eckart Wolfgang U. 
Published: October 2006

AbstractWhen Imperial Germany entered the group of European colonial powers in 1884, among her enthusiastic physicians the question arose how the white man, as a representative of a vulnerable race, could be able to exist permanently in tropical regions. It is not surprising that German colonial circles especially the representatives of the organized German colonial movement were taking a keen interest in the same question. The Deutsche Kolonialgesellschaft (German Colonial Society) inaugurated and financed international questionaire‐activities in the field of tropical medicine with the intention of supporting the institutionalization of this new medical discipline. In fact, the foundation of the Hamburg Institut für Schiffs‐ und Tropenkrankheiten in 1901 was not only a consequence of the specialisation of bacteriology but also an expression of the grasp of colonial politics for tropical medicine as an instrument of colonization. Ever since up to the loss of the imperial Schutzgebiete (protectorates) German tropical medicine has been in a very close connection with colonial politics. Its tasks ranged from the organization of medical infra‐structures at the colonial periphery to the delivery of instruments for the imperial process of acculturation or the supply with pseudo‐scientific arguments for racial discrimination. The spectrum of these tasks will be outlined in this paper, and the interdependency of German colonial politics and German colonial medicine will be discussed.