bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenergic Agents, II1): 1‐Aryl‐N2‐alkyl‐ethanediamines as Isosters of Adrenergic Arylethanolamines
Authors: Berger Sarah , Nudelman Abraham
Published: October 2006

A family of 1‐aryl‐N2‐alkyl‐ethanediamines 1 isosteric with the N‐alkyl‐arylethanolamines are described. Although the prepared compounds were generally less potent than the N‐alkyl‐arylethanolamines, the 1‐aryl‐N'‐(phenylmethyl)‐N‐alkyl‐1,2‐ethanediamines derivatives 6, are more active than the debenzylated free amino analogs 1, which may be indicative of the importance of the lipophilicity of the substituent at the alpha position to the aromatic ring.
Reaction of Some 1,2,4‐Triazines with Acetobromoglucose
Authors: Eid Mohga M. , Abdel Hady Sayed A. , Ali Hosny A. W.
Published: October 2006

2,3,4,6‐Tetra‐O‐acetyl‐α‐D‐glucopyranosyl bromide (1) reacts with 5‐benzyl‐3‐phenyl‐1,2,4‐triazin‐6(1H)thiones 6a‐d and 4‐aryl‐6‐benzyl‐3‐thioxo‐2,3,4,5‐tetrahydro‐1,2,4‐triazin‐5‐ones 11a‐g to give the corresponding N‐glucosyl derivatives 7a‐d and 12a‐g, respectively. The structures of these glucosides were established by chemical and spectroscopic methods.
Synthesis of Novel 2‐Substituted Quinoline Derivatives: Antimicrobial, Inotropic, and Chronotropic Activities
Authors: Farghaly A. M. , Habib N. S. , Khalil M. A. , El‐Sayed O. A. , Bistawroos A. E.
Published: October 2006

Three novel series of quinoline derivatives have been prepared by cyclization of the intermediate 3‐(13‐dioxolan‐2‐yl)‐2‐substituted thiocarbamoyl‐hydrazinoquinolines with different α‐halocarbonyl compounds. These series are: 3‐(1,3‐dioxolan‐2‐yl)‐2‐(3‐substituted‐4‐phenylthiazolin‐2‐ylidene)hy‐drazinoquinolines; 3‐(1,3‐dioxolan‐2‐yl)‐2‐(3‐substituted‐5‐ethoxycarbonyl‐4‐methylthiazoline‐2‐ylidene)hydrazinoquinolines and 3‐(1,3‐dioxolan‐2‐yl)‐2‐(3‐substituted‐4‐thiazolidinon‐2‐yl)hydrazinoquinolines. The active methylene group of the latter series was used for the preparation of their arylidene derivatives. The antimicrobial as well as inotropic and chronotropic activities of the prepared compounds were studied.
Untersuchungen an 1,4‐Naphthochinonen, 20. Mitt.1): Droseron, Ether und Isomere aus Juglon
Authors: Wurm Gotthard , Geres Uwe
Published: October 2006

Droseron (13) und sein Stellungsisomer 14 werden rationell durch radikali‐sche Methylierung der isomeren Diacetate 11 und 12 synthetisiert. Die 3‐bzw. 2‐Methylether 4/3 von Droseron bzw. Isodroseron entstehen regiospezifisch aus 13/14 durch Titration mit CH2N2, die 5‐Methylether 17 und 18 durch saure Hydrolyse der Dimethylether 15 und 16. Die optimalen Herstellungsverfahren für die Ausgangsstoffe 3‐ und 2‐Hydroxyjuglon (9 und 10) führen über die Addition von CH3OH an Juglon (20) in saurem, oxidierenden Milieu bzw. an 3‐Chlorjuglon (22) unter alkalischen Reaktionsbedingungen.
Synthesis of Vinca Alkaloids and Related Compounds, XLIV1): Synthesis of Trifluoro‐apovincaminic Acid Ester
Authors: Incze Märia , Sóti Ferenc , Kardos‐Balogh Zsuzsanna , Kajtár‐Peredy MÁRia , Szántay Csaba
Published: October 2006

Via the intermediate iminium salt 8 the 21,21,21‐trifluoro‐apovincaminic acid ethyl ester (2), a derivative of CAVINTONR (1) was synthesized. The pharmacological effect of 2 changed dramatically compared with the parent compound.
The Reactions of Pindolol, Mepindolol, Carazolol, and Related Model Compounds with Triethyl Orthoformate: Pathways and Products of a New Colour Reaction
Authors: Pindur Ulf , Witzel Helmut
Published: October 2006

The acid‐catalysed electrophilic tandem substitutions of pindolol, mepindolol, and carazolol and some related model compounds with triethyl ortho formate give rise to new derivatives from the trishetaryl methan series. In some cases also further functionalised heterocycles were isolated. The structural aspects of the new trishetarylmethanes were discussed as C3‐symmetric molecular propellers, respectively. The importance of the described reaction as colour reaction was mentioned.
Bestimmung von Formaldehydspuren in wäßrigen Lösungen Determination of Traces of Formaldehyde in Aqueous Solutions
Authors: Spreitzer Helmut , Jäger Walter
Published: October 2006

Im Zuge der Untersuchungen an Herzklappentransplantaten1) bestimmten wir die Glutaraldehyd‐Freisetzung mit dem Hydrazin 1 als Reagens2).
Molecular Pharmacological Aspects of Antiarrhythmic Activity, II1): Interaction of Class I Compounds with Calmodulin
Authors: Mannhold Raimund , Voigt Werner , Bast Aalt , Timmerman Hendrik
Published: October 2006

We have tested the calmodulin (CaM) inhibitory potency of class I antiarrhythmics in the phosphodiesterase (PDE) assay. The lipophilicity of the test compounds has been quantified by two experimental (log P, RM) and two calculative (Σf, C log P) procedures. Five antiarrhythmics (asocainol, aprindine, lorcainide, propafenone, and ethmozine) exhibit IC50 values < 250 μM for the inhibition of the CaM‐stimulated PDE activity. Lipophilicity seems to be a prime, but not the sole descriptor of CaM inhibitory potency. The functional means of CaM inhibition by the test compounds for their antiarrhythmic properties remains to be clarified in further investigations.
Synthesis and Reactions of 2(5)‐[Benzyl or Cyanomethyl]‐1,3,4‐oxadiazoles
Authors: Hamad M. M.
Published: October 2006

A series of five membered heterocycles, namely 5‐(benzyl or cyanomethyl)‐3‐acetyl‐2,2‐disubstituted‐1,3,4‐oxadiazolines (3a‐e), 2,5‐disubstituted‐1,3,4‐oxadiazoles (4a, b), 2‐hydroxy‐5‐(benzyl or cyanomethyl)‐1,3,4‐oxadiazoles (5a, b), 1,2,5‐trisubstituted‐1,3,4‐triazoles (6a, b), and 2‐(benzyl or cyano‐methyl)‐1,3,4‐oxadiazole‐5‐thiols (10a, b), were synthesized. Also 5‐chloro‐2‐benzyl‐1,3,4‐oxadiazole 7 was prepared. Reaction of amines, hydrazines, and sodium azide with 7 gave the corresponding 2‐arylamino (8a, b), 5‐hydrazino or phenylhydrazino (8c, d) and 2‐azido derivatives 9, respectively. Mannich bases (11a, b) were prepared by the reaction of sec. amines with 9a. 5‐Carboxymethylthio‐1,3,4‐oxadiazoles (12a, b) and their ethyl esters (13a, b) were also prepared. The ester 13a reacted with amines and hydrazines to give the corresponding amides (14a‐d).
Hydrolysis and Oxidation of 1H‐Benzotriazole‐carboxylic Acid Esters by Rat Liver Microsomes
Authors: Jacobi Sylvia , Hoffmann Hermann
Published: October 2006

The 1H‐benzotriazole‐carboxylic acid esters under investigation were almost ‐ with the exception of the tert.‐butylester ‐ completely hydrolyzed by rat liver microsomes. Some substrates were metabolically oxidized to a very small extent (< 1 %) yielding small amounts of possibly toxic metabolites after inhibition of the esterases with paraoxone.
Anellierte Thiopyrone, 6. Mitt.: 2‐Acyl‐thiopyrone aus 1‐Indanon, 3‐Cumaranon und Thioindoxyl
Authors: Görlitzer Klaus , Vogt Regina
Published: October 2006

Ausgehend von den Thiopyranon‐2‐carbonsäuren 1 gelingt in einer 4‐stufigen Synthese die Darstellung der 2‐Formyl‐thiopyrone 7. Diese lassen sich über ihre Oxime 9 und Nitrile 10 zu den Tetrazolen 11 umsetzen. Die Boran‐Reduktion der Thiopyranon‐2‐carbonsäureester 2 führt diastereoselektiv zu den Diolen 5. Die alkalische Hydrolyse von 2d liefert das Disulfid 8.
Eine neue Synthese von 8‐donatorsubstituierten 5‐Thia‐ und 5‐Deaza‐riboflavin‐Derivaten
Authors: Fenner Helmut , Hochhuth Dieter
Published: October 2006

Durch gezielte Verwendung von Schutzgruppen konnte die Synthesemöglichkeit für 5‐Thia‐ und 5‐Deaza‐riboflavine auch auf die 8‐Elektronendonator‐substituierten Derivate 2 und 3 ausgedehnt werden. Die Polyole 4 werden transketalisiert und anschließend mit 2,4,6‐Trichlorpyrimidin zu 8 und 9 umgesetzt Einführung der Benzyloxy‐Gruppe und Hydrierung gibt als zentrale Vorstufen die Uracile 11. Deren Cyclisierung erfolgte in bekannter Weise. Abspaltung der O‐Schutzgruppen gibt die Zielverbindungen 2 und 3. Die Methode mit 3–7% Gesamtausbeute (bezogen auf D‐Ribose) kann auch Synthesemöglichkeiten für komplexere Flavine eröffnen, da sich die Uracile 11 auch zu “normalen” Flavinen cyclisieren lassen.
Glutaraldehydrückstände in Herzklappentransplantaten
Authors: Spreitzer Helmut , Jäger Walter , Grimm Michael , Eybl Elisabeth , Müller Matthias
Published: October 2006

Herzklappentransplantate aus Kälberperikard erleiden im Laufe der Zeit Schäden durch Mineralisation. Diese Schäden und mögliche toxische Nebenwirkungen können eventuell auf Glutaraldehydrückstände, die aus der notwendigen Vorbehandlung stammen, verursacht werden. Unterschiedliche Waschmethoden, die vor der Transplantation durchgeführt werden, wurden hinsichtlich ihrer Fähigkeit, Glutaraldehyd zu entfernen, untersucht.
2‐Amino‐2‐oxazolines, III: Synthesis, Structure, and Preliminary Pharmacological Evaluation of Cycloaddition Compounds with Unsaturated Carboxylic Esters
Authors: Forfar Isabelle , Jarry Christian , Leger Jean‐Michel , Carpy Alain
Published: October 2006

The reaction of 5‐substituted 2‐amino‐2‐oxazolines with unsaturated carboxylic esters yielded 2,3,5,6‐tetrahydro‐ and 2,3‐dihydro‐7H‐oxazolo[3,2‐a]pyrimidin‐7‐ones. The structure of these compounds was established by IR‐ and NMR‐spectra and by X‐ray crystallography. They were tested for anti‐arrhythmic and hypocholesterolemic activities.
Potentiell ZNS‐wirksame, tricyclische Verbindungen mit verbrücktem Mittelring, 4. Mitt.: Synthese und Konfiguration von partiell hydrierten 9,10‐Epithioanthracen‐S‐oxiden
Authors: Linde Hermann F. G. , Krämer Norbert H.
Published: October 2006

Es wird über Arbeiten zur Darstellung von 9,10‐Epithioanthracensulfoxiden berichtet. Als Oxidationsmittel wurden Natriummetaperiodat, Wasserstoffperoxid/Essigsäure und Oxone® verwendet. Für die endo‐Verbindungen wurde mittels Einsatz von Eu(FOD)3 die thermodynamisch stabilere anti‐Konfiguration ermittelt. Eine Isomerisierung von 8‐anti in 8‐syn gelingt mit Hilfe von Trimethyloxoniumtetrafluoroborat, ist aber bereits bei 0°C vollständig reversibel. Die Konfigurationen in der exo‐Reihe wurden durch 1H‐NMR‐Spektroskopie aus denen der endo‐Verbindungen abgeleitet.
Syntheses of Metabolites of S‐Carboxymethyl‐L‐cysteine and S‐Methyl‐L‐cysteine and of Some Isotopically Labelled (2H, 13C) Analogues
Authors: Meese Claus O. , Specht Dagmar , Hofmann Ute
Published: October 2006

The chemical syntheses of human metabolites of S‐carboxymethyl‐L‐cysteine (3) and S‐methyl‐L‐cysteine (12) are described. The additional preparation of some 2H‐ and 13C‐labelled isotopomers enabled the direct evaluation of the stabilities of 3 and 12 under physiological conditions and also facilitated the unambiguous assignments of the signals in the 13C‐NMR spectra of all compounds mentioned.
Asymmetrische elektrophile α‐Amidoalkylierung, 8. Mitt.: Gewinnung optisch aktiver α‐Phenacylpyrrolidinamide und erste asymmetrische Totalsynthese des Norruspolins
Authors: Wanner Klaus T H. , Höfner Georg
Published: October 2006

Durch Reaktion des chiralen nicht‐racemischen α‐Methoxyamids 1 mit den Silylenolethern 2a‐d werden stereoselektiv die α‐Phenacylpyrrolidinamide (R)‐4/(S)‐5a‐e synthetisiert. Die geminalen Bisamide (R)‐12/(S)‐13 werden durch Umsetzung von 1 mit dem Bistrimethylsilylimidat 11 erhalten. (R)‐4d wird für die Gewinnung des optisch aktiven Norruspolins (R)‐16 (ee ≧ 84%) eingesetzt.
Einfluß des Vasokonstriktors Glycylpressin auf die Verfügbarkeit von Mitomycin C
Authors: Czejka Martin , Jäger Walter , Schüller Johann
Published: October 2006

Im Rahmen einer intra‐arteriellen Chemotherapie von Patienten mit Lebermetastasen wurden die Blutspiegelverläufe von Mitomycin C (1) nach Verschluß der Arteria hepatica communis durch den Vasokonstriktor Glycylpressin (2) ermittelt. Der Gefäßverschluß mit 2 führt bei gleicher Dosierung im Gegensatz zu einer Bolusgabe von 1 ohne 2 zu signifikant (p < 0.01) erniedrigten Blutspiegelwerten. Durch diese Verringerung der systematischen Verfügbarkeit um rund 50% wird die Verfügbarkeit im Tumorbereich entsprechend gesteigert.
In vitro Testing of Triamterene Derivatives for Antiarrhythmic Activity
Authors: Busch Andreas E. , Ullrich Frank , Mutschler Ernst
Published: October 2006

A series of para‐substituted triamterene derivatives (Table 1) were evaluated for their antiarrhythmic properties in vitro. Pharmacological evaluation of the compounds and some class‐I‐ (quinidine, lidocaine, and propafenone) as well as class‐III‐antiarrhythmic drugs (±)‐sotalol and amiodarone was carried out by measuring the functional refractory period (FRP), the maximal driving frequency (MDF) and the force of myocardial contractions (FC) of electrically stimulated guinea pig atria. The increase in FRP and the decrease in MDF was most pronounced with the class‐I‐antiarrhythmic drugs, but these compounds showed the typical negative inotropic effects, too. For the class‐III‐antiarrhythmics only a weak influence on FRP and MDF could be demonstrated, while FC was not altered in the presence of (±)‐sotalol and amiodarone. Neutral substituted triamterenes like compounds 2—5 as well as most of the benzyltriamterene derivatives showed similar or stronger effects on FRP and MDF as (±)‐sotalol and amiodarone. With the exception of 4 and 5, these effects were combined with an increase of FC. Compounds 6 and 7, well known potent diuretics, showed no influence to FRP, MDF and FC. Therefore, we conclude different mechanisms for the antikaliuretic and cardiac activity.
Zur Reaktion von Nifedipin mit Pyridiniumbromidperbromid
Authors: Görlitzer Klaus , Bartke Ulrich , Schmidt Eckhardt
Published: October 2006

Nach derYoung‐Methode wird aus Nifedipin das 1,4‐Dihydropyridin‐bislacton4hergestellt. Als Nebenprodukt dieser Reaktion werden die Pyridiniumverbindung3sowie die bromierten 1,4‐Dihydropyridinlactone5und6isoliert.4wird durch Redox‐ und photochemische Reaktionen charakterisiert. Die Halbstufenpotentiale der Dihydropyridin‐ und Pyridin‐Verbindungen werden bestimmt.
Synthesis and Calcium Antagonistic Activity of Some New 2‐Thioxo‐1,2,3,4‐tetrahydropyrimidine Derivatives
Authors: Ertan Mevlüt , Balkan Ayla , Saraç Selma , Uma Serdar , Renaud Jean Francois , Rollad Yves
Published: October 2006

A series of 1,2,3,4‐tetrahydro‐6‐methyl‐4‐(substituted phenyl)‐2‐thioxo‐5‐pyrimidinecarboxylic acid methyl esters were synthesized by condensing thiourea with methyl acetoacetate and nonsubstituted or differently substituted benzaldehydes in absol. ethanol using HCl as a catalyst according to the Biginelli reaction. The structures of the compounds were confirmed by elemental and spectroscopic analysis. ‐ The compounds were evaluated for their calcium antagonistic activity on the basis of their potency in inhibiting [3H] PN 200—110 binding on microsomes obtained from rat skeletal muscle.
N‐[4‐(3H‐1,3,4‐Oxadiazoline‐2‐thion‐5‐yl)phenyl]‐N′‐substituted Thioureas: Synthesis and Antimicrobiological Activities
Authors: Rollas Sevim , Büyüktimkin Servet , Çevikbas Adile
Published: October 2006

Diverse pharmacological properties are associated with 3H‐1,3,4‐oxadiazoline‐2‐thione derivatives. These include anticonvulsant1—4) and fungicidal5) properties. On the other hand thiourea derivatives possess antiphytoviral6), virucidal7), growth inhibitory8—10), and herbicide11) activities. All these data prompted us to combine these moieties into a single molecule. The compounds synthesized were tested for their antimicrobial activities against seven microorganisms.
Properties and Reactions of Substituted 1,2‐Thiazetidine 1,1‐Dioxides: Fluoride Catalyzed Reactions of Silylated β‐Sultams with Electrophiles
Authors: Müller Martin , Otto Hans‐Hartwig
Published: October 2006

N‐Silylated β‐sultams 1 and 4 react with ketones and aldehydes in the presence of fluoride ions to O‐silylated carbinolsulfonamides 3. Under similar conditions, N‐aminoalkylated 4‐silylated β‐sultams react to O‐silylated C‐4 aldol adducts 7, which are deprotected and desilylated to 8 and 10. The (α‐hydroxy‐α‐methylethyl)‐substituted β‐sultam 16 is prepared from 14 via 15. Reactions of 5b and 14 with aromatic aldehydes yield the Peterson olefination products 11, 12, and 19. E‐ and Z‐isomers of these compounds are separated by CC.
Synthesis of New Benzimidazole Derivatives as Potential Antimicrobial Agents
Authors: Badawey El‐Sayed A. M. , Hassan Ahmed M. M. , Kappe Thomas
Published: October 2006

Barbiturates 3 as possible antimicrobial agents were obtained by reacting the N,N′‐disubstituted urea 1a or the thiourea analogues 1b,c with the magic malonates 2a,b. On the other hand, reaction of 1a with ethoxycarbonyl isocyanate (4) yielded the substituted s‐triazine‐2,4,6(1H,3H,5H)‐trione 5. The reaction of 4 with 2‐aminomethyl‐benzimidazole (6) gave the allophanate 7 which upon treatment with Na2CO3 yielded N‐(1H‐benzimidazol‐2‐yl)urea 8.
Rapid Assay for the Quantification of Piretanide in Biological Fluids
Authors: Spahn‐Langguth Hildegard , Hahn Gabriele , Mutschler Ernst
Published: October 2006

Piretanide was determined from plasma and urine using reversed‐phase high‐performance liquid chromatography. Plasma was extracted with diethylether at pH 4 using bumetanide as internal standard. The chromatographic separation was performed on an octadecylsilane column (ODS) with acetonitrile/pH 7 phosphate buffer (3:7, v/v). In order to determine piretanide in urine, bumetanide was added to a urine aliquot. Then the sample was centrifuged and the supernatant directly injected without extraction followed by chromatography on an ODS column with a mixture of methanol and pH 7 phosphate buffer (12:13, v/v). The compounds were detected by their intrinsic fluorescence, monitoring the eluate at 287/450 nm. Total chromatography times were 8 min for plasma and 13 min for urine samples. The method was applied for the assay of piretanide in plasma of healthy volunteers after i.v. or p.o. dosage of 6 mg piretanide.
Synthesis and Binding Properties to GABA Receptors of 3‐Hydroxypyridinyl‐ and 3‐Hydroxypiperidinyl‐Analogues of Baclofen
Authors: Desideri Nicoletta , Galli Alessandro , Sestili Isabella , Stein Maria Luisa
Published: October 2006

The synthesis of 3‐(3‐hydroxy‐2‐pyridinyl)propanoic acid, 3‐(3‐hydroxy‐2‐pyridinyl)‐4‐aminobutanoic acid, their corresponding piperidine compounds, and of some cyclized derivatives is described.

In in vitro assays none of the new compounds shows any noteworthy affinity for GABAA or GABAB receptors; only (R,S)‐3‐(3‐hydroxy‐2‐pyridinyl)‐4‐aminobutanoic acid and its lactam inhibited in some degree [3H]GABA binding, at 10−4 M concentration, with low specificity as regards the two receptors.
Analysis of Drugs by Polarography, XXXV: The Polarographic Behaviour of Cinolazepam. [1‐(2‐Cyanoethyl)‐7‐chloro‐3‐hydroxy‐5‐(2‐fluorophenyl)‐1,3‐dihydro‐2H‐1,4‐benzodiazepin‐2‐one] and Assay of its Tablets
Authors: Oelschläger H. , Volke J. , Belal F.
Published: October 2006

Cinolazepam is reduced at the Dropping Mercury Electrode (DME) over the entire pH range in Britton Robinson buffers (BRB) containing 20% DMF as a solubilizer. A well‐defined cathodic wave is obtained over the pH range 3‐5, which is very suitable for analytical purposes. The wave was characterized as being irreversible, diffusion‐controlled and free from adsorption phenomena. In acid buffers, 4 electrons are consumed in the reduction process, while in alkaline buffers the electrode reaction is somewhat complicated. Tablets containing 40 mg cinolazepam were analysed using the polarographic and a developed HPLC method. The results obtained with both methods are in good accordance as revealed by statistical analysis. The details of the complicated mechanism of the reduction process at the DME are still under investigation but elucidated in principle.
Synthesis, Decarboxylation, and Nitrosation of 1‐Acyl‐2‐pyrrolidone‐3‐carboxylic Acids: A Convenient Novel Entry to 2,3‐Dioxopyrrolidine Derivatives
Authors: Gailius Viktoras , Stamm Helmut
Published: October 2006

Esters 1 of 1‐acyl‐2‐pyrrolidone‐3‐carboxylic acids 2 were hydrolized to 2 with acetic acid/HCl at 60–70°C. Reaction of 1a with formic acid/HCl at 60–75°C led to (not isolated) 2a which began to decarboxylate to 3a during the conversion of 1a to 2a even at this low temp. Decarboxylation of 2c‐f was accomplished at 160°C without solvent. Decarboxylative nitrosation of 2c‐f yielded the oximes 4c‐f of 1‐acyl‐2,3‐dioxopyrrolidines. Treatment of 4f with magic methyl provided the enol ether 5f of the respective dioxopyrrolidine.
Pyridazines, LVII: Synthesis and Cyclocondensation Reactions of (2‐Aminophenyl)‐(4‐pyridazinyl)‐ketone, a New Diaza Isoster of 2‐Aminobenzophenone
Authors: Haider Norbert , Heinisch Gottfried , Moshuber Jöran
Published: October 2006

A convenient approach to the new 2‐aminobenzophenone analogue 4 is reported. Condensation reactions of 4 with ortho esters or amide acetals, respectively, followed by intramolecular cyclisations were found to provide smooth access to (4‐pyridazinyl)‐substituted quinolines 10, 13a,b, and the quinazoline derivative 15.
Researches on Antibacterial and Antifungal Agents, XIV: Thiophene Analogues of Bifonazole
Authors: Stefancich Giorgio , Silvestri Romano , Retico Augusta , Artico Marco , Simonetti Giovanna
Published: October 2006

Some thiophene analogues of bifonazole have been synthesized by standard procedures and their antifungal activity has been tested against Candida albicans. Among test derivatives biphenyl‐4‐yl‐5‐chloro‐thien‐2‐ylimidazol‐1‐ylmethane and its 5‐deschlorothien‐2‐yl analogue resulted to be the most active. Their antifungal potency was almost comparable to that of control substances, such as miconazole, ketoconazole, and bifonazole. Replacement of benzene by the pyrrole ring in the biphenyl portion retained almost quantitatively the antifungal activity, whereas substitution with other azoles and with nitrogen alicyclic rings led always to less potent derivatives.
Kurzmitteilungen: Passiflora and Lime‐blossoms: Motility Effects after Inhalation of the Essential Oils and of Some of the Main Constituents in Animal Experiment.
Authors: Buchbauer G. , Jirovetz L. , Jäger W.
Published: October 2006

Passionsblume und Lindenblüten: Motorik bei Tieren nach Inhalation der ätherischen Öle und einiger Hauptbestandteile
Relationship of Hypolipidemic and Antineoplastic Activities of Tricyclohexyl‐ and Triphenylphosphine Boranes, Carboxyboranes, Cyanoboranes, and Related Derivatives
Authors: Das Mrinal K. , Maiti Pradip K. , Roy Sarbari , Mittakanti Malaiah , Morse Karen W. , Hall Iris H.
Published: October 2006

A series of tricyclohexyl‐ and triphenylphosphine boranes, carboxyboranes and cyanoboranes were synthesized. These compounds have potent hypolipidemic effects, antineoplastic and antiinflammatory activities in rodents. Furthermore, they demonstrated potent cyctotoxicity against standard human tissue culture lines. The compounds which afforded the best hypolipidemic activity, i.e. greater than 40% reduction of serum cholesterol and triglyceride levels, were diphenyl‐(4‐methylphenyl)‐phosphine borane and triphenylphosphine carboxyborane. Other derivatives demonstrated more potent antineoplastic activity against the Ehrlich ascites carcinoma growth including triphenylphosphine cyanoborane, 2‐amino‐4‐methyl‐pyridine cyanoborane and 2‐amino‐pyridine cyanoborane. Most of the derivatives showed good activity against murine L1210 lymphoid leukemia, Tmolt3 human leukemia, uterine HeLaS cells, and human glioma cell growth. Select compounds were active against colon adenocarcinoma, KB nasopharynx, lung bronchogenic and osteosarcoma cell growth. Tricyclohexyl‐ and triphenylphosphine boranes and the carboxy derivatives of the latter borane demonstrated good antiinflammatory activity.
An Efficient Synthesis of Buspirone and its Analogues.
Authors: Cybulski Jacek , Chilmonczyk Zdzislaw , Szelejewski Wieslaw , Wojtasiewicz Krystyna , Wróbel Jerzy T.
Published: October 2006

Eine leistungsfähige Synthese von Buspiron und Buspiron‐ähnlichen Verbindungen
Zur bromometrischen Bestimmung von Vinylbital
Authors: Görlitzer Klaus , Boventer Kristin
Published: October 2006

Vinylbital (1) reagiert mit Br−/BrO3− in Eisessig/HCl unter Addition von BrCl zu 2. Der Ersatz von HCl durch HBr führt zur Dibrom‐Verbindung 4, die unter O‐Alkylierung zum Furo[2, 3‐d]pyrimidin 5 cyclisiert.
Untersuchungen an Lokalanästhetika, 99. Mitt.: Synthese und lokalanästhetische Wirkung von Alkoxyphenylcarbamaten
Authors: Búciová Lubiča , Csöllei Jozef , Račanská Eva , Švec Pavel
Published: October 2006

Zum Studium des Einflusses von Veränderungen der Verbindungskette in einer Gruppe von Lokalanästhetika wurde eine Serie von 24 Verbindungen aus der Gruppe der 1‐Propoxymethyl‐2‐(1‐pyrrolidinyl)‐, 2‐(1‐Piperidino)‐und 2‐(1‐Perhydroazepinyl)‐ethylester der o‐ und m‐Alkoxyphenylcarbamidsäure hergestellt. Die untersuchten Verbindungen wiesen bei verhältnismäßig geringer akuter Toxizität hohe relative anästhetische Aktivität im Vergleich mit den Standardverbindungen Cocain und Procain auf.
Synthesis and Antimicrobial Activity of 3‐(Substituted‐phenyl)‐sydnones
Authors: Moustafa M. A. A. , Eisa H. M.
Published: October 2006

3‐(3 or 4‐Acetylphenyl)‐sydnones 7, 8 have been synthesized by formation of the glycines 3, 4, followed by nitrosation to 5, 6 and cyclization with acetic anhydride to sydnones. Sydnone derivatives carrying chalcone moieties 15, 16 were prepared by formation of the chalcone analogues 11, 12 through condensation of the glycines 3, 4 with the appropriate aldehydes, followed by the reactions applied for the preparation of 7, 8. The sydnone derivatives were screened for antimicrobial activities.
Amino Acids, XII: (±)Pipecolic Acid Derivatives ‐ Part 2: An Expedient Synthetic Entry to Substituted Pipecolic Acids
Authors: Herdeis Claus , Engel Wolfram
Published: October 2006

The Diels‐Alder product 1 is transformed by Noyori reaction and catalytic hydrogenation to 4. Hydrolysis with concomitant decarboxylation of 4 furnishes the trans configuration amino acid 5. Functional group transformation (reduction, lactonization) of 5 provides 7, ring opening affords the pipecolic acid derivative 9. On the other hand 1 is hydrolyzed to 10 and 4‐oxo‐pipecolic acid 11. Reduction of 10 and subsequent hydrolysis with decarboxylation of 12 affords the amino acid 13a/13b in a cis/trans ratio of 1:1. Contrary to this result, reduction of 11 provides 13a/13b in a ratio of ≧ 95/5.
Synthesis of Pyranoid Analogues of the Anti‐HIV Active 3′‐Deoxy‐2′,3′‐didehydrothymidine (D4T)
Authors: Hansen H. Bue , Pedersen Erik B. , Vestergaard Bent Faber
Published: October 2006

The primary hydroxy group of ethyl 2,3‐dideoxy‐α‐D‐erythro‐hex‐2‐enopyranoside (1) was selectively protected and the secondary hydroxy group was deoxygenated via the dithiocarbonate 3 from which ethyl 6‐O‐(4‐methoxybenzoyl)‐2,3,4‐trideoxy‐α‐D‐trideoxy‐α‐2‐enopyranoside (4) and its regioisomer (5) were produced. These were converted into didehydro nucleosides by glycosylation of silylated heterocyclic bases in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst. The configurations of the anomeric products were assigned by 1H‐NMR analysis of the corresponding saturated compounds which were obtained by hydrogenation of the double bond in the carbohydrate moiety. The compounds 9a,b,d, 10a, b, 14a,b,e,f, and 15a,b,e,f did not show any significant activity against HIV or HSV‐1.
Ringverengung von 1,4‐Benzodiazepinen zu 3,4‐Dihydrochinazolinen bei präparativer Elektrolyse (Beispiel 5: Cyprazepam
Authors: Oelschläger Herbert , Martienssen Doris , Belal F.
Published: October 2006

Cyprazepam (1) wird in 3 Stufen unter Verbrauch von insgesamt 6 θ an der DME und auch im präparativen Maßstab an einer gerührten Hg‐Kathode reduziert. Dabei tritt unter Eliminierung von Cyclopropylmethylamin Ringverengung zum 6‐Chlor‐2‐methyl‐4‐phenyl‐3,4‐dihydrochinazolin ein. Dies ist das fünfte Beispiel einer zuerst von uns beobachteten reduktiven Ringverengung, die nur an einer Hg‐Elektrode, nicht aber bei der katalytischen Hydrierung eintritt.
Aminopeptidase Inhibitory Properties and Analgesic Activity of (2S,3,7‐3,7‐Diamino‐2‐hydroxy‐heptanoic Acid Containing Tripeptide Analogues of the N‐Terminal Tripeptide of Probestin
Authors: Herranz Rosario , Vinuesa Soledad , Pérez Concepción , García‐López M. Teresa , De Ceballos María L. , Murillo Francisco M. , Del Río Joaquín
Published: October 2006

(2S,3R)‐3,7‐Diamino‐2‐hydroxy‐heptanoyl‐Leu‐Pro‐OH [(2S,3R)‐DAHHA‐Leu‐Pro‐OH, 4], analogue of the N‐terminal tripeptide of probestin, has been synthesized, and tested as inhibitor of AP‐B, Leu‐AP, AP‐M, and enkephalin‐degrading APs, and as analgesic. In order to establish structure‐activity relationships the dipeptide (2S,3R)‐DAHHA‐Pro‐OH (5) and the tripeptide (2S, 3R)‐DAHHA‐Ala‐Pro‐OH (6) were also prepared. Compounds 4 and 6 were potent and selective inhibitors of enkephalin‐degrading APs and showed a prolonged antinociceptive effect.
2‐Amino‐2‐oxazolines, VI: Study of the Tautomerism by Experimental and Theoretical Methods
Authors: Forfar Isabelle , Jarry Christian , Fayet Jean‐Pierre , Carpy Alain
Published: October 2006

The tautomeric equilibrium of 2‐amino‐2‐oxazolines with a C‐5 lateral amino chain has been studied by dipole moments measurement and theoretical calculations (MNDO and ab initio). The results show the predominance of the amino tautomers in solution. The X‐ray crystal structure of 5‐morpholinomethyl‐2‐amino‐2‐oxazoline confirms this tendency in the solid state.
Biotransformation of the Sympathomimetic Tetraminol in vitro
Authors: Drandarov Konstantin , Kvasničková Eva , Hais I. M.
Published: October 2006

On incubation with the postmitochondrial fraction of the liver homogenate of rabbits, guinea‐pigs, rats, and mice in the presence of NADPH and oxygen, the α‐sympathomimetic trans‐3‐(2‐hydroxyethylamino)‐5,8‐dimethoxy‐1,2,3,4‐tetrahydro‐2‐naphthol (Tetraminol, 1) is preferentially O‐demethylated in position 8, yielding metabolite 3. In male rats O‐demethylation is stronger than in females.
Synthesis of Biologically Active [2.2]Paracyclophanes
Authors: Aly Ashraf A. , Hassan Alaa A. , Mourad Aboul‐Fetouh E. , Hopf Henning
Published: October 2006

Claisen reaction of 4‐acetyl[2.2]paracyclophane (1) with ethyl acetate and diethyl oxalate affords 4‐acetoacetyl[2.2]paracyclophane (2) and ethyl(4‐oxaloacetyl[2.2]paracyclophane) (6), respectively. Reaction of 2 and 6 with hydrazines and CuCl2 gave the pyrazole derivatives 4 and 8 in addition to the metal complexes 5 and 9. Mannich reaction of 2 with benzylamine and paraformaldehyde yielded the piperidinone derivative 3. The biological activity of all new compounds was tested.
Heterocyclische Spirocyclohexadienone, 1. Mitteilung
Authors: Möhrle Hans , Schake Dieter , Bluhme‐Hensen Karin
Published: October 2006

Die als Methylenamin 3 beschriebene Verbindung wird als heterocyclisches Spirocyclohexadienon 9 erkannt, wobei die katalytische Hydrierung entgegen den Literaturangaben nicht zum Methylaminderivat 4, sondern zum Spiroketon 10 und einem Gemisch diastereomerer, spirocyclischer Alkohole 11a/11b führt. Die Reaktivität von 9 gegenüber Protonensäuren und Carbonylreagentien wird untersucht.
Untersuchungen zur Benzylierung von Tetrahydroisochinolinen mit Benzaldehyd bzw. substituierten Benzaldehyden (Rügheimer‐Burrows‐Reaktion)
Authors: Dannhardt Gerd , Roelcke Julius
Published: October 2006

Die unter Aromatisierung verlaufende Benzylierung von Piperidin‐ bzw. Tetrahydroisochinolin‐Derivaten mit Benzaldehyden (Rügheimer‐Burrows‐Reaktion) ist eine vielstufige Reaktion, für die verschiedene Mechanismen diskutiert werden. Durch die Isolierung und Charakterisierung der nachfolgend beschriebenen Intermediate bzw. Nebenprodukte werden Teilschritte der Gesamtsequenz plausibel erklärbar.
Zur Pharmakokinetik von Lipidsenkern, 9.Mitt.: Zur Frage der biliären Ausscheidung des Lipidsenkers Ciprofibrat (1) (2‐[4‐(2,2‐Dichlorcyclopropyl)‐phenoxy]‐2‐methylpropionsäure)
Authors: Oelschläger Herbert , Rothley Dietrich , Schröder Dieter , Scherm Sabine
Published: October 2006

Nach oraler Gabe von 200 mg Ciprofibrat (1) an 10 cholezystektomierte Patienten, denen ein T‐Drain in den Ductus choledochus eingelegt worden war, findet sich 1 in der im 12 h‐Rhythmus gesammelten Galle nur als 1‐ O‐β‐Acylglukuronid in sehr geringer Menge. Approximative Berechnungen ergaben, daß nach Einzeldosis in 2 Tagen weniger als 0.5% der verabfolgten Dosis biliär exkretiert wurden. Ob bei Langzeittherapie die biliäre Ausscheidung zunimmt, ist noch eine offene Frage.
Oxazepines and Thiazepines, XXV: Chemical Transformations of 2,3‐Dihydro‐1,5‐benzothiazepin‐4(5H)‐ones
Authors: Lévai Albert
Published: October 2006

2,3‐Dihydro‐1,5‐benzothiazepine‐4(5H)‐thiones 13‐22 were prepared by the reaction of the appropriate 2,3‐dihydro‐1,5‐benzothiazepin‐4(5H)‐ones with Lawesson's reagent. N‐Acyl (23‐25) and N‐alkyl (26‐28) derivatives have also been synthesized. Oxidation with 3‐chloroperoxybenzoic acid afforded sulfoxides 29‐32, and sulfones 33‐40 were obtained by using H2O2 as an oxidizing agent.
Synthesen von 13C‐ und 14C‐markiertem trans‐2‐Amino‐2‐methyl‐N‐(4‐nitroxycyclohexyl)‐propionsäureamid (BM 12.1179)
Authors: Neidlein Richard , Strein Klaus , Preßmar Friedburg , Kramer Walter , Michel Helmut
Published: October 2006

Von dem gefäßwirksamen Salpetersäureester trans‐2‐Amino‐2‐methyl‐N‐(4‐nitroxycyclohexyl)‐propionsäureamid (BM 12.1179) (1) sind, ausgehend von der sterisch gehinderten α‐Aminoisobuttersäure (2), die 13C‐ und 14C‐markierten Verbindungen synthetisiert worden. Verschiedene Amino‐Schutzgruppen sowie Methoden zur Aktivierung der Carboxylfunktion werden verglichen.
Preparation and Diuretic Properties of Novel Amiloride Analogues
Authors: Russ Thomas , Ried Walter , Ullrich Frank , Mutschler Ernst
Published: October 2006

Fifteen novel amiloride analogues were synthesized and their diuretic properties compared to amiloride and triamterene in white wistar rats. Whereas none of the 6‐substituted derivatives exhibited significant natriuretic and antikaliuretic effects, five of the compounds modified in the 2‐position were found equal or better than standards. The results are discussed with respect to chemical structure and physicochemical properties.
Synthesis of Some Guanylhydrazones and Imidazolinylhydrazones as Thromboxane‐Synthase and Platelet Aggregation Inhibitors
Authors: Desideri N. , Sestili I. , Piccardoni P. , Rotondo S. , Cerletti C. , Stein M. L.
Published: October 2006

The imidazolinylhydrazones of (3‐pyridinyloxy)‐acetaldehyde and of 6‐[3‐(2‐formyl‐pyridinyl)oxy]hexanoic acid were synthesized as cyclic analogues of the corresponding guanylhydrazones which were found to be selective inhibitors of human thromboxane‐synthase. The benzene isosters were also prepared in order to define the importance of the ring nitrogen for the activity.‐ Moreover, the guanyl‐ and imidazolinyl‐hydrazones of two 6‐[(3‐pyridinyl)oxy]hexanoic acids showing in the 2 position an alkyl chain with an α,β‐unsaturated ketonic function were prepared.‐ Imidazolinylhydrazones 7 and 18 are selective inhibitors of thromboxane‐synthase, while the two guanylhydrazones 14 and 15 which do not affect prostanoid biosynthesis seemed to be antagonists at the thromboxane receptor.
Hypolipidemic Effects of 2‐Furoic Acid in Sprague‐Dawley Rats
Authors: Hall Iris H. , Wong Oi T. , Reynolds David J. , Chang J. J.
Published: October 2006

2‐Furoic acid was shown to be effective in lowering both serum cholesterol and serum triglyceride levels significantly in rats with an elevation of HDL cholesterol level at 20 mg/kg/day orally. LDL receptor activity was reduced in hepatocytes, aorta foam cells, small intestinal epithelium cells and fibroblasts. HDL receptor activity was elevated in the rat hepatocytes and small intestinal cells. These activities were correlated with inhibition of acyl CoA cholesterol acyl transferase activity. Neutral cholesterol ester hydrolase activity was elevated in rat hepatocytes and human fibroblasts. Thus, 2‐furoic acid appears to interfere directly with activity of intracellular enzymes rather than affecting high affinity‐mediated lipoprotein membrane receptors. In vivo treatment with 2‐furoic acid led to reduction in the liver and small intestine ATP dependent citrate lyase, acetyl CoA synthetase, acyl CoA cholesterol acyl transferase, sn‐glycerol 3‐phosphate acyl transferase, phosphatidylate phosphohydrolase and heparin induced lipoprotein lipase activities.

2‐Furoic acid reduced biliary cholesterol levels but the agent increased bile salts which are lithogenic. Acute toxicity studies in mice suggest that the agent has some hepatic toxicity effects. The LD50 was relatively low at 250 mg/kg IP in mice.
Microsomal N‐Oxygenation of Adenine to Adenine 1‐N‐Oxide
Authors: Clement Bernd , Kunze Thomas
Published: October 2006

During investigations on the N‐oxygenation of adenine (1) the enzymatic formation of adenine 1‐N‐oxide 3 was demonstrated for the first time. The identity of this metabolite was confirmed by its chromatographic behaviour and UV‐spectrum recorded after HPLC separation. Adenine 1‐N‐oxide (3) and similar oxygenated derivatives of adenine were synthesized as reference substances. The enzymatic formation of 3 exhibits the typical characteristics of a reaction catalysed by microsomal mono‐oxygenases. In induction experiments, an increase in the rate of formation of 3 after pretreatment with phenobarbital was observed. A participation of those isoenzymes of the cytochrome P‐450 enzyme system which can be induced by phenobarbital is assumed.
Lactone, 23. Mitt.: Synthese und Stereochemie „γ‐lactonisierter”︁ Neuroleptika vom Butyrophenon‐Typ
Authors: Lehmann Jochen , Radwansky Anja
Published: October 2006

„γ‐Lactonisierte”︁ Neuroleptika (1,2a‐c) können aus den α‐Formyl‐, α‐Carboxy‐ und α‐Methylenlactonen 5‐7a,b durch Umsetzen mit den Aminen 8a‐c erhalten werden. 6a und 1a‐c fielen als cis/trans‐Gemische mit über‐wiegender cis‐Form, 6b und 2a als cis/trans‐Gemische mit überwiegender trans‐Form an. Bei 2b,c wurden reine trans‐Isomere isoliert.
Stereoselektive Synthese neuer zentral wirksamer Tricyclen vom Benzomorphan‐Typ mit 2‐Phenylethylamin Partialstruktur
Authors: Wünsch Bernhard , Höfner Georg , Bauschke Gerd
Published: October 2006

Die Addition des mit LDA deprotonierten Glycinesters 6 an das Homophthalaldehydmonoacetal 5 liefert den β‐Hydroxyester 7, der sich nach Reduktion zu den racemischen 2,6‐Epoxy‐3‐benzoxocin‐5‐aminen (+/−)‐12 und (+/−)‐13 cyclisieren läß. Die Schlüsselverbindungen für die Gewinnung von 12 und 13 in enantiomerenreiner Form sind die Hydroxyacetale (R,S,R)‐22 und (R,S,S)‐23: (R,S,R)‐22 läßt sich stereoselektiv durch Addition der Aryllithiumverbindung 21b bzw. der Aryltitanverbindung 21c an das neue Serinal‐Äquivalent (R,S)‐20 gewinnen; die Reduktion des Ketons (R,S)‐24 mit LiAlH4 bei −78°C führt überwiegend (>95%) zu dem diastereomeren Hydroxyacetal (R,S,S)‐23. Mit Säure werden (R,S,R)‐22 und (R,S,S)‐23 in die tricyclischen Urethane (S,S,R)‐25 und (R,S,S)‐30 überführt, die sich zu den Dimethylaminen (S,S,R)‐12 und (R,S,S)‐13 reduzieren und methylieren lassen (ee > 97%). Analog werden die enantiomeren Amine (R,R,S)‐12 und (S,R,R)‐13 ausgehend von (R)‐Serin dargestellt. Die relative Konfiguration von (R,S,R)‐22 wird mit Hilfe von Molecular Dynamics Rechnungen (Sybyl 5.4) in Kombination mit NOE‐Messungen bewiesen.‐ Nach Applikation beider Enantiomere von 12, 13, 27 und 32 lassen sich bei Mäusen typische Symptome für eine zentrale Dämpfung beobachten. Im Essigsäure Writhing‐Test sind (S,S,R)‐12, (S,R,R)‐13, (R,S,S)‐13, (S,S,R)‐27, (R,R,S)‐27 und (R,S,S)‐32 stark analgetisch wirksam mit ED50 Werten in der Größenordnung des ED50‐Wertes von Tramadol‐HCl.
2,6‐Epoxy‐3‐benzazocine: Zentral wirksame N/O‐Acetale durch Ringschluß von Amino‐ und Amidoacetalen
Authors: Wünsch Bernhard , Höfner Georg , Bauschke Gerd
Published: October 2006

Unter sauren Bedingungen cyclisierten die sekundären Amine 10a und 10b, das primäre Amin 15, das Amid 17a und das Urethan 17b zu den 2,6‐Epoxy‐3‐benzazocinen 11a, 11b, 16, 18a und 18b. Der Ringschluß des inversen Amids 5a zum tricyclischen N/O‐acetal 6 gelang jedoch nicht. Mit LiAlH4 ließ sich die Epoxybrücke des Urethans 18b zum bicyclischen 3‐Benzazocin 20 öffnen. ‐ Während das N‐(2‐Methoxyethyl)‐Derivat 11b das Verhalten der Mäuse nicht beeinflußte, zeigte das N‐Methyl‐Derivat 11a starke ZNS‐Wirkung.
Nonsteriodal Antiinflammatory Agents, XVII: Inhibition of Bovine Cyclooxygenase and 5‐Lipoxygenase by N‐Alkyldiphenyl‐pyrrolyl Acetic and Propionic Acid Derivatives
Authors: Dannhardt G. , Lehr M.
Published: October 2006

A series of 19 N‐alkyl‐diarylpyrrolyl‐acetic and ‐propionic acid derivatives was synthesized and tested. Using bovine blood as enzyme source the inhibition of cyclooxygenase and 5‐lipoxygenase, respectively, was applied to determine the antiinflammatory activity. In general all compounds tested inhibit 5‐lipoxygenase more effectively than cyclooxygenase. A structure‐activity relationship is discussed.
Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XIX: 4,4′‐Phenylene‐bis‐sydnone Imines
Authors: Rehse Klaus , Kämpfe Michael , Martens Antje
Published: October 2006

Fourteen 4,4′‐m‐phenylene‐ and two 4,4′‐p‐phenylene‐bis‐sydnone imine hydrochlorides have been synthesized. All compounds exhibited good solubility in water. In the m‐series the 3‐(3‐phenylpropyl)‐derivative 5c and the 3‐hexyl compound 51 showed antiplatelet activities at or below 10 μmol/L (IC50, Born‐test with collagen). The corresponding p‐compounds had the same (61) or slightly lower (6c) activity. No effect on the fibrin formation (Quick‐test) could be observed.
Cer(IV)oxidationen von β‐Aminoketonen, 8. Mitt.: Synthese von im Piperidinteil verschieden substituierten 1,2,3,4‐Tetrahydroisochinolinen
Authors: Holzgrabe Ulrike , Inkmann Elisabeth
Published: October 2006

1‐ und 3‐alkyl‐ und/oder arylsubstituierte 1,2,3,4‐Tetrahydroisochinoline sind durch oxidative Cyclisierung von N‐Benzyl‐β‐aminoketonen mit Cer(IV)sulfat zugänglich. In nahezu allen Fällen werden Diastereomerengemische erhalten. Nach Austausch der Ketofunktion des Aminoketones gegen COOR‐, CN‐, CHO‐ oder NO2‐Gruppen gelingt unter den Standardreaktionsbedingungen keine Cyclisierung, da die Hydrolyse zu N‐Benzyl‐N‐methylaminopropionsäure und die Oxidation in benzylischer Stellung zu Benzaldehyden und Benzoesäuren Überhand gewinnt. Im Fall der Oxidation des Benzylaminopropionaldehydacetal‐Derivates 1k wurde ein Isochinolindion 4k isoliert.
Zyklische Harnstoffe, 2. Mitt.: Racemate und Enantiomere von Imidazolidin‐2‐onen Synthese, Konfiguration und sedativ‐hypnotische Wirkung
Authors: Knabe Joachim , Büch Horst P. , Biwersi Joachim
Published: October 2006

Die Racemate und die Enantiomere der Imidazolidin‐2‐one 2a und 2b, die man als zyklische Harnstoffe auffassen kann, werden aus den Racematen und den Enantiomeren der Hydantoine 1a und 1b durch Reduktion mit LiAlH4/AlCl3 gewonnen. Die in Ethanol rechtsdrehenden Enantiomere von 2a und 2b besitzen S‐Konfiguration. ‐ In Versuchen an Wistar‐Ratten waren 2a und 2b sedativ‐hypnotisch wirksam. Zwischen den Enantiomeren traten beachtliche enantioselektive Wirkungsunterschiede auf.
High‐Performance Liquid Chromatographic Analysis of Cyclosporine A in Human Skin
Authors: Husek Aleš , Eibler Ernst , Wiegrebe Wolfgag
Published: October 2006

A three‐dimensional high‐performance liquid chromatography (HPLC) method is described for the determination of cyclosporine A in human skin. The method allows to determine at least 3 ng cyclosporine A in 10 mg skin (total sample amount needed) and is suitable for cyclosporine A level monitoring in the skin of psoriatic patients.
Dimethyl 3,3′‐(4‐Methyl‐1,3‐naphthylene)dipropionate as a Singlet Oxygen Trap in Biological Systems
Authors: Müller Klaus , Ziereis Klaus
Published: October 2006

The utility of dimethyl 3,3′‐(4‐methyl‐1,3‐naphthylene)dipropionate (DMNDP) as a singlet oxygen trap in biological systems is described. The determination of the rate constant for the reaction of DMNDP with singlet oxygen in acetonitrile gave a value of 9.8 · 10−7 M−1s−1; the half‐life of the corresponding endoperoxide at 37°C in phosphate buffered saline is 412 min. DMNDP does not possess sensitizing properties, and its usefulness for the detection of singlet oxygen is demonstrated in the photooxidation of liposomes by 5,10,15,20‐tetraphenyl‐21H, 23H‐porphine (TPP).
Synthesis and Anti‐HIV Activity of 5‐Alkoxymethyl‐3′‐azido‐2′,3′‐dideoxyuridines
Authors: Abdel‐Megied Ahmed E.‐S. , Hansen Poul , Pedersen Erik B. , Nielsen Claus , Nielsen Carsten M.
Published: October 2006

Methyl 3‐azido‐5‐O‐tert‐butyldiphenylsilyl‐2,3‐dideoxy‐D‐erythro‐furanoside (3) was coupled with silylated 5‐hydroxymethyluracil (1a) and its C1‐C6 alkyl ethers 1b–g to give the corresponding protected nucleosides 4a‐g which were deprotected with Bu4NF to afford 3‐azido nucleosides 5a‐g and 6a‐g. The α‐anomers 6f,g show moderate activity against HIV. No significant activity against HSV‐1 was found for the compounds 5 and 6.
Synthesis and Evaluation of Sulfur‐Containing Glutethimide Derivatives for Aromatase and Desmolase Inhibitory Activity
Authors: Bednarski Patrick J. , Hartmann Rolf W.
Published: October 2006

Novel sulfur‐containing glutethimide derivatives, substituted with either thiol or methylsulfide groups in the ortholpara positions of the aromatic ring, were synthesized and tested for both human placental aromatase and bovine adrenocortical desmolase inhibitory activities. The synthesis was achieved by the chlorosulfonation of gluthethimide, which yielded a 3:1 mixture of the para to ortho sulfonyl chlorides 2a/b. The sulfonyl chlorides of gluthethimide were reduced with Zn/H2SO4 to give the thioglutethimides 3a/b, which in turn were methylated with MeI/EtOH to give the corresponding methylsulfides 4a/b. In comparison to aminoglutethimide (AG). 3a/b and 4a/b were weak inhibitors of aromatase, with 3a/b being more potent than 4a/b. Aromatase inhibition by the thiol compound was pH‐dependent; 3a/b was most potent at higher pH (7.4) than at lower (6.6). This suggested that the thiolate form of 4 coordinates with the ferric heme of aromatase. Likewise, both 3a/b and 4a/b were less potent at inhibiting bovine adrenal desmolase than AG. Possible reasons for the surprisingly poor aromatase inhibitor activity of these compounds are discussed.
Synthesis and Biological Activity of Bromolignans and Cyclolignans
Authors: Feliciano Arturo San , Medarde Manuel , de Clairac Rafael Pelaez Lamamie , López Jose Luis , Puebla Pilar , Gravalos M Dolores García , Lázaro Pilar Ruiz , de Quesada M Teresa García
Published: October 2006

Nine lignan derivatives (4‐12) have been obtained from (‐)‐yatein by treatment with DDQ and NBS. They showed moderate antineoplastic activity (P‐388, A‐549, HT‐29) compared with podophyllotoxin, but some of them have a better therapeutic index. None of the tested compounds shows antiviral (HSV‐1, VSV) or enzyme inhibitor (ADA, DHFR, GST) activities.
Properties and Reactions of Substituted 1,2‐Thiazetidine 1,1‐Dioxides: Alkylation and Acylation of 3‐Haloalkyl β‐Sultams and Synthesis of Bicyclic β‐Sultams
Authors: Schwenkkraus Peter , Otto Hans‐Hartwig
Published: October 2006

Alkylation of the 3‐chloroethyl substituted β‐sultam 1 with bromoacetates yields the N‐ and 3‐substituted β‐sultams 2; exchange of halogens affords esters 3. Reactions of 1 or of the analogues 8 with isocyanates make the carbamoyl derivatives 5, 6, and 9 available. While cyclization of 6 with n‐BuLi in the presence of HMPT yields the bicyclic β‐sultams 7, the analogous reaction of 9 failed. The bicyclic β‐sultams 12 and 14 are obtained from 3‐hydroxyalkyl β‐sultams 11 and 13 and carbonyl compounds. None of the prepared β‐sultams showed any antibacterial activity.
Heterocyclisch anellierte Indolizine durch intramolekulare [3 + 2]‐Cycloaddition mit Nicotinium‐dicyanmethyliden
Authors: Seitz Gunther , Tegethoff Ralph
Published: October 2006

Thermisch induzierte intramolekulare [3 + 2]‐Cycloadditionsreaktionen der Nicotinium‐dicanmethylide 4a‐c, die am Pyrrolidinstickstoff mit verschieden langen ω‐Alkinseitenketten substituiert sind, führen in guten Ausbeuten zu entspr. neuen, heterocyclisch anellierten Indolizinen 6‐8. Das mit einem aktivierten Seitenkettendipolarophil versehene Dicyanmethylid 9 liefert neben dem Indolizin 11 in geringen Mengen das Naphthyridin 14.