bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmakokinetik von 5‐Fluorouracil nach i. v.‐Gabe unter Berücksichtigung der Erythrozyten
Authors: Czejka Martin , Schüller Johann , Fogl Ulrike
Published: October 2006

Die in vivo Bindung des Zytostatikums 5‐Fluorouracil (1) an Erythrozyten wurde im Blut von Patienten untersucht. Der Einfluß der Erythrozyten auf die vaskuläre Verfügbarkeit von 1 beträgt (bezogen auf die AUC0–60‐Werte) 38. 6 ± 7. 2% für die Erythrozyten, der Erythrozytenverteilungskoeffizient beträgt 0. 65 ± 0. 18. Das Verteilungsvolumen und die totale Clearance von 1 werden durch die Erythrozyten erhöht, die Halbwertszeiten der Verteilung aus dem Kompartiment und der terminalen Elimination bleiben jedoch unberührt.
Synthesis and Preliminary Pharmacological Study of Thiophene Analogues of the Antipyretic and Analgesic Agent Ethenzamide
Authors: Darias V. , Bravo L. , Abdallah S. S. , Mateo C. C. Sánchez , Expósito‐orta M. A. , Lissavetsky J. , Manzanares J.
Published: October 2006

A preliminary pharmacological study of a thiophene analogue 1b of the analgesic and antipyretic agent Ethenzamide and of a closely related compound 1a showed that a great similarity exists among Ethenzamide and the thiophenic compounds for analgesic, antipyretic, ulcerogenic, hypothermic, and sedative effects. However, the acute toxicity in mice for the thiophenic compounds is notably higher than that of Ethenzamide.
Dichloro‐[1‐(hydroxyphenyl)‐2‐phenylethylenediamine]platinum(II) Complexes: Testing on the Human Ovarian Cancer Cell Lines NIH: OVCAR 3 and SK OV 3
Authors: Bernhardt Günther , Müller Richard , Gust Ronald , Reile Herta , Keller Christoph , Spruß Thilo , Schönenberger Helmut
Published: October 2006

The diastereoisomeric dichloro‐[1‐(2‐, 3‐ and 4‐hydroxyphenyl)‐2‐phenyl‐ethylenediamine]platinum(II) complexes were tested on two human ovarian cancer cell lines NIH: OVCAR‐3 and SK‐OV‐3, both resistant against cisplatin. Dichloro‐[threo‐1‐(3‐hydroxyphenyl)‐2‐phenylethylenediamine]platinum(II) (threo‐5‐PtCl2) proved to be the most active representative of the new series, producing cytocidal effects at a concentration range of 2. 5 to 5. 0 μM on the NIH: OVCAR‐3 cell line. On the more resistant SK‐OV‐3 cell line, threo‐5‐PtCl2 was only moderately active, while in combination with BSO, a GSH level lowering compound, threo‐5‐PtCl2 showed a strong synergistic effect.
Benzo[b]thiophenes, Part I: Synthesis and Antimicrobial Activity of Benzo[b]thienyl‐1,3,4‐oxadiazole, ‐1,2,4‐triazoline, and ‐thiazoline Derivatives
Authors: Aboulwafa Omaima M. , Berto Fatma A. G.
Published: October 2006

Four new series of benzo[b]thiophene derivatives bearing various thiosemicarbazide, 1,3,4‐oxadiazole, 1,2,4‐triazoline, and thiazoline moieties have been synthesized and evaluated for antimicrobial activity.
Gleichgewichte kondensierter Oxadiazine über Iminium‐Oximat‐Zwischenstufen in Lösungen
Authors: Möhrle Hans , Ottersbach Dirk , Steigel Alois
Published: October 2006

Die Hg(II)‐Dehydrierung des A3‐Piperidein‐oxims 4 führt wie die des Hydroxypiperidin‐oxims 6 zu dem Hydroxyoxadiazin 5. Bei Verwendung von Methanol/Wasser‐Gemischen als Lösungsmittel resultiert zusätzlich zu 5 noch das Methoxyderivat 11. NMR‐Untersuchungen an 5 und 11 in CDCI3 und DMSO‐d6 zeigen, daB sich in Lösung jeweils ein Gleichgewicht von diastereomeren Formen einstellt, was eine Iminium‐Oximat‐Zwischenstufe 12 erfordert.
Facile Synthesis of Fused Heterocycles through 2‐Bromobenzofurylglyoxal‐2‐arylhydrazones
Authors: Abdelhamid Abdou O. , Ghabrial Sami S. , Zaki Mayssoune Y. , Ramadan Nazmy A.
Published: October 2006

Several new imidazo[1,2‐a]pyridine, pyrazolo[5,1‐a]imidazole, quinazolinone, 1,4‐benzothiazine, and pyrazole derivatives were synthesized by the reaction of 2‐bromobenz‐2‐furylglyoxal‐2‐arylhydrazones with different reagents. The structures of the new heterocycles were based on elemental analysis and spectral data.
Naphthalenes as Water‐Soluble Singlet Oxygen Carriers and Detectors: Hydrophobic and Kinetic Properties
Authors: Müller Klaus , Ziereis Klaus
Published: October 2006

The syntheses of endoperoxides of naphthalene derivatives with propionic acid and ethanesulfonic acid side chains are described. The partition coefficients and half‐lives for the thermal decomposition in phosphate buffer of all compounds have been determined. Because of their high stability in phosphate buffer at 37°C, 3,3′‐(4‐Methyl‐1,3‐naphthylene)dipropionic acid and its corresponding methyl ester may be used as chemical traps for the detection of 1O2 in biological systems.
3‐Amino‐4‐arylazopyrazoles: CT Complexation and a Novel Synthesis of Pyrazolo[2,3‐a]quinazolines
Authors: Ibrahim Yusria R. , Hassan Alaa A. , Mohamed Nasr K. , Mourad Aboul‐Fetouh E.
Published: October 2006

3,5‐Diamino‐4‐arylazopyrazoles 1a‐d form charge‐transfer (CT) complexes with chloranil (CHL), fluoranil (TFQ) and react with 2,3‐dicyano‐5,6‐dichlorobenzoquinone (DDQ) to yield pyrazolo[2,3‐a]quinazoline derivatives 4. 5‐Amino‐3‐phenyl‐4‐arylazopyrazole 2a‐d form CT‐complexes only with DDQ.
Amino Acids, XI: (±)Pipecolic Acid Derivatives ‐ Part 1: The [4+2] Cycloaddition Pathway
Authors: Herdeis Claus , Engel Wolfram
Published: October 2006

[4+2] Cycloadditions of various dienes 1 with the acceptor‐substituted imines 2 furnished the 4‐oxo‐piperidine‐2,2‐dicarboxylate derivatives 3, 5, 11, 12. All efforts to get the regio‐isomeric 5‐oxo‐derivatives (Scheme 2) by variation of the reaction conditions and substitution pattern of 1 and 2 resulted in differing amounts of ring‐open products 4, 6, 8, 10. This is in contradiction to results of another group4a).
Synthese neuer Indolmethanamine durchLeimgruber‐BatchoReaktion
Authors: Stanetty Peter , Koller Herbert
Published: October 2006

Es wird über eine kurze und effiziente Synthese der Titelverbindungen aus‐gehend von den käuflichen Carbonsäuren1bzw.5berichtet. Durch gezielte Modifikationen der Reaktionsbedingungen bei der im Schlüsselschritt eingesetztenLeimgruber‐BatchoReaktion konnten auch stabile 1‐Hydroxy‐indol‐Derivate isoliert werden.
New Indole and Triazino[5,4‐b]indol‐4‐one Derivatives: Synthesis and Studies as Inotropics and Inhibitors of Blood Platelet Aggregation
Authors: Monge Antonio , Aldana Ignacio , Font Maria , Angel Arraras José , Santiago Esteban , José Lopez‐Unzu Maria , José Martínez de Irujo Juan , Alberdi Elena , Fernández‐Alvárez Eldiberto
Published: October 2006

New triazino[5,4‐b]indol‐4‐one derivatives carrying amino groups in position 3 were synthetized and tested as inotropic agents and inhibitors of platelet aggregation. 2h, 2p, 5p, and 6g are the most active as inotropic agents.

Compounds were tested as inhibitors of platelet aggregation induced by adenosine 5'‐diphosphate (ADP) and arachidonic acid (AA) (guinea pig whole blood). 2k, 2p, 5o, 6d, 6m, and 6o are the most active as inhibitors of the platelet aggregation induced by AA. 6d, 6h, and 6o are most active compounds also in the aggregation induced by ADP.

Radioinmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on compounds 2b, 2d, 2f, 2g, 2h, 2i, 2k, 2m, 2o, 2p, 2r, 5i, 5j, 5k, 5r, and 5f, which inhibit platelet aggregation induced by AA. None of the compounds tested turned out to be selective inhibitors.

Compounds 2h and 2p showed both inotropic and platelet aggregation inhibiting activity.
Bioavailability Study of Two Different Verapamil Formulations
Authors: Horne C. , Stenzhorn G. , Blume H. , Knauf H. , Mutschler E.
Published: October 2006

Relative bioavailability and bioequivalence of two oral verapamil preparations were investigated (dosage 80 mg, film‐coated tablets as reference, dragées as test formulation). The clinical study was performed in a 2‐period‐cross‐over design with 16 male healthy volunteers (mean age 28.8 ± 3 years). The active metabolite norverapamil was included in the investigation. To assess bioequivalence several pharmacokinetic characteristics (i. e. AUC(o‐co), Cmax, tmax) were taken into account. Shortest 90% confidence intervals were calculated based on parametric (ANOVA, ANOVAlog) and non‐parametric (Wilcoxon, Mann‐Whitney) statistical tests. A positive decision for bioequivalence was accepted if the confidence intervals did not exceed the limits of 80‐120% for AUC and 70‐130% for Cmax. A mean relative bioavailability of 127% for the test preparation was found. Thus, bioavailability of the dragées is marked higher than bioavailability of the filmcoated tablets.
Beiträge zur chemischen Reaktivität einer neuen Verbindungsklasse
Authors: Eger Kurt , Frey Martina
Published: October 2006

Die chemische Reaktivität cytostatisch wirksamer 5‐Indolonderivate wird untersucht, um Vorstellungen über ihr Verhalten in biologischen Systemen zu erhalten. Versuche zur Dienon‐Phenol‐Umlagerung mißlingen, bei der Aromatisierung von 1b entsteht das Phenolderivat 3α. Hydrolyse der Indolone 1a,b mit wäßriger NaOH führt zur Esterverseifung (4a,b). In konz. H2SO4 werden die Säureamide 5a,b,d erhalten. In ethanolischer HCl bilden sich die Ammoniumsalze 6a,b,d. Acylierung von 1a zu 8 weist das endocyclische N‐Atom als nukleophiles Zentrum aus. Starke Elektrophile wie Benzaldehyd addieren an 1b in Pos. 4, schwächere wie Acetylendicarbonsäuredimethylester (ADC) reagieren erst nach Nitrilverseifung (5b,d) zu 11 und 12. Nukleophile wie Wasser, Ethanol, n‐Propylamin addieren an die Δ6‐Doppelbindung zu 14–16.
Assessment of Anti‐HIV Activity of Some Benzimidazolylthiazoles
Authors: Badawey Elsayed A. M. , Hazzaa Ali A. , Rida Samia M. , Fahmy Hesham T. Y.
Published: October 2006

Benzimidazolylthiazoles 2 were synthesized by condensing 1H‐benzimidazole‐2‐acetonitrile (1) with sulphur and isothiocyanates. The syntheses of the Schiff bases 3, thioureas 4, and thiazolopyrimido[1,6‐a]benzimidazoles 5 and 6 are also described. Seven compounds were evaluated in vitro against human HIV, however, no significant activity was observed with any of these compounds.
Synthesis and Biological Activity of N‐2 Alkylamino Derivatives of 4,5‐Dihydro‐s‐triazolo[3,4‐d]‐1,5‐benzothiazepine
Authors: Ambrogi Valeria , Giampietri Antonio , Grandolini Giuliano , Perioli Luana , Ricci Maurizio , Tuttobello Lorenzo
Published: October 2006

The synthesis of a new series of N‐2 alkylamino derivatives of 4,5‐dihydro‐s‐triazolo[3,4‐d]‐1,5‐benzothiazepine has been accomplished starting from 2,3‐dihydro‐1,5‐benzothiazepin‐4(5H)ones and their 2‐methyl and 2‐aryl derivatives. ‐ All the compounds were tested in vitro for their antimicrobial activity, but none of them showed remarkable activity. ‐ The tricyclic compounds 7a‐j, 8a‐j, 9a‐j, 10a‐j, and 11a‐j were also screened for their CNS activity in mice and several of them showed interesting activity.
Enantioselektivität der Biotransformation eines neuen Theophyllinderivats
Authors: Harsche Christian , Oelschläger Herbert , Engel Jürgen
Published: October 2006

7‐((RS)2‐1‐Methyl‐2‐phenylethylamino)propyl)‐theophyllin 3 läßt sich vorteilhafter durch reduktive Aminierung von 7‐Acetonyltheophyllin (4) mit (RS)‐Amphetamin (2) (Diastereomerenverhältnis 1:1) als durch SN‐Reaktion von Proxyphyllintosylat mit (RS)‐2 darstellen (Diastereomerenverhältnis 9:1).

3 ist infolge sterischer Hinderung praktisch kein Prodrug mehr für die intermediäre Bildung von (RS)‐2 (Ratte). Die Enantioselektivität des nach oraler Gabe im 24‐h Harn in Mengen von ca. 1% der Dosis aus 3 gefundenen (RS)‐2 wurde HPLC auf einer Cyclobond‐Säule über seine Isoindolderivate, gebildet aus o‐Phthalaldehyd, Thioglykolsäure und 2, zu 65.2% (Bereich 63–68%) S(+)‐ und 34.8% R(‐)‐Amphetamin (Bereich 32–37%) bestimmt.
Removal of the Pyrrolidine Group by Dehydrogenation of a 4‐Pyrrolidin‐2‐yl‐tetrahydroisoquinoline
Authors: Mahboobi Siavosh , Seidl Engelbert , Wiegrebe Wolfgang
Published: October 2006

Dehydrogenation of 6,7‐dimethoxy‐1‐methyl‐4‐(N‐methyl‐pyrrolidin‐2‐yl)‐3,4‐dihydroisoquinoline (9) by Pd/C in tetraline leads to dehydrogenated products, rearrangement, and elimination of the pyrrolidine group mainly as N‐methylpyrrolidine (Scheme 3).
Antibacterial and Antifungal Agents, XV: Synthesis and Antifungal Activity of Structural Analogues of Bifonazole and Ketoconazole
Authors: Stefancich Giorgio , Artico Marino , Ortar Giorgio , Silvestri Romano , Simonetti Giovanna , Apuzzo Germana , Artico Marco
Published: October 2006

The synthesis and antifungal activities of the cis‐ and trans‐1‐acetyl‐4‐{4‐[[2‐(1,1′‐biphenyl‐4‐yl)‐2‐(1H‐imidazol‐1‐ylmethyl)‐1,3‐dioxolan‐4‐yl]‐methoxy]phenyl}piperazines 3 and 4 are reported. Stereochemical assignments to diastereomeric pairs of cis/trans isomers were made on the basis of 1H‐ and 13C‐NMR data. Among test derivatives the best activity was shown by the benzoyl esters of the cis‐ and trans‐[2‐(1,1′‐biphenyl‐4‐yl)‐2‐(1H‐imidazol‐1‐ylmethyl)‐1,3‐dioxolan‐4‐yl]methanols 9 and 10.
N‐Phosphorylierte Aminosäuren als potentielle Zytostatika
Authors: Schwieger Jochen Franz , Unterhalt Bernard
Published: October 2006

Durch nucleophilen Angriff von 2‐(1‐Ethylenimino)‐carbonsäure‐methylestern 1 auf POCl3 oder Umsetzung von Aminosäuremethylester‐hydrochloriden 2 mit POCl3 werden die Phosphorsäureamid‐dichloride 3 erhalten. Nachfolgende Reaktionen mit Ethylenimin oder Aziridinopropanol 6 führen zu den TEPA®‐Analogen 4 bzw. zu den IFOSFAMID®‐analogen 1,3,2‐Oxazaphosphorinen 5, deren Wirksamkeit an einem Tumormodell (P388‐Leukämie, CD2F1‐Maus) untersucht wird.
Massenspektrometrische Untersuchungen an Derivaten der Phenylessigsäure, 4. Mitt.: Abspaltung ortho‐ständiger Substituenten aus ionisierten Phenyl‐2‐propanonen nach Elektronenstoßaktivierung
Authors: Striegel Hans‐Günter , Mayer Klaus K. , Wiegrebe Wolfgang , Schlunegger Urs Peter , Siegrist Phillip , Aebi Beat
Published: October 2006

Die Molekülionen der Phenyl‐2‐propanone 2a‐4a verlieren positionsspezifisch o‐ständige Cl ‐, Br‐ bzw. I‐Atome unter Bildung von (M‐HaI.)+‐Ionen (m/z 133) hoher Intensität (70/12 eV; 1. und 2. FFR) und identischer Struktur (MIKE‐CAD‐Spektren). Die Fragmentionen bei m/z 133 aus o‐Chlorphenyl‐2‐propanon (2a) und 2,2‐Dimethyl‐2,3‐dihydro[b]furan (11) sind von ähnlicher, aber nicht identischer Struktur. Die stoßaktivierten (2. FFR) (M‐Br)+‐Ionen aus o‐Bromphenyl‐2‐propanon (3a) und 1‐Brom‐1‐phenyl‐2‐propanon (12) liefern praktisch deckungsgleiche Spektren. Die Hauptreaktion der (M‐Hal)+‐Ionen aus 2a‐4a ist die Abspaltung von CO, das ausschließlich das C‐Atom der Carbonylgruppe enthält (13C‐Markierung). Der mechanistische Verlauf der Reaktionsfolge wird diskutiert (Abb. 5 und 8).
Determination of the Stereochemistry of Chemotherapeutics Derived from 5‐Nitrofurfural: NOE Difference Spectroscopy as a Simple and Reliable Method
Authors: Holzer Wolfgang
Published: October 2006

Homonuclear NOE difference spectroscopy is shown to be a rapid and reliable tool for the determination of stereochemistry regarding the ‐C=N‐ substructure of 5‐nitrofurfural derivatives of type 1–10, including several known chemotherapeutic agents. The assignments resting on the NOE difference experiments are in full agreement with those based on 13C‐NMR data.
Reaktionsmechanismus der Hydantoinsynthese nach Biltz, 2. Mitt.: Einfluß der Substituenten auf die Umlagerungsrichtung
Authors: Schwenker Gerhard , Guo Hong
Published: October 2006

Aus den 1‐13C‐markierten 4‐monosubstituierten Benzilen 1a‐c wurden mit den Harnstoffen 3a‐d 5‐Aryl‐5‐phenylhydantoine 6a‐c bzw. 3‐substituierte 5‐Aryl‐5‐phenylhydantoine 9a‐i als Isotopomerengemische dargestellt. Massen‐ und 13C‐NMR‐spektrometrisch wird die Verteilung der 13C‐Markierung auf C‐4 und C‐5 ermittelt. Wie bei der Benzilsäureumlagerung wandert auch hier der 4‐Methyl‐ bzw. 4‐Methoxyphenylrest weniger leicht als der unsubstituierte Phenylrest und dieser weniger leicht als der 4‐Chlorphenylrest. Der Unterschied zwischen Phenyl‐ und 4‐Chlorphenylrest ist allerdings nur klein und kehrt sich in einem Fall sogar geringfügig um. Der Einfluß der Substituenten auf die Richtung der Umlagerung wird mit einer thermodynamischen Steuerung der Reaktion durch vorgeschaltete Gleichgewichte (Schemata 2 und 3) erklärt.
Dithio‐ und Thionester, 54. Mitt.: Versuche zur Darstellung von α‐Aminodithiosäureestern mit der Bislactimether‐Methode
Authors: Hartke Klaus , Brutsche Andreas
Published: October 2006

Die Sulfhydrolyse von 2,5‐Bis(methylthio)‐3,6‐dihydropyrazin (5) liefert 2,5‐Piperazindithion (8) und nicht Glycindithiomethylester (6). Die durch Alkylieren von 5 erhaltenen Iminiumsalze 9 werden von H2S in die 1,4‐Dialkyl‐2,5‐piperazindithione 10 übergeführt. 5 bildet mit Chlorameisensäuremethylester 2,5‐Bis(methylthio)‐pyrazin (11) und mit Acetanhydrid das 1,4‐Dihydropyrazin 12. Die Sulfhydrolyse der 6‐ und 7‐Ring‐Iminiumsalze 14 führt zu den Thiolactamen 15.
Alkaloids of Cynanchum vincetoxicum: Efficacy against MDA‐MB‐231 Mammary Carcinoma Cells
Authors: Tanner Ulrike , Wiegrebe Wolfgang
Published: October 2006

Alkaloids 1‐4 from Cynanchum vincetoxicum (asclepiadaceae) (Scheme 1) do not have affinity to the oestrogen receptor but they inhibit the growth of the hormone‐independent mammary carcinoma cells MDA‐MB‐231 (Fig. 1) and bind to nucleosides and nucleotides (Table 1). Intercalation was not observed.
Zyklische Harnstoffe, 1. Mitt.: Racemate und Enantiomere von Hexahydropyrimidin‐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 Hexahydropyrimidin‐2‐one 2a‐2e, die man auch als zyklische Harnstoffe auffassen kann, werden aus den Racematen und den Enantiomeren der Barbiturate 1a‐1e durch Reduktion mit LiAlH4/AlCl3 gewonnen. Die in Ethanol rechtsdrehenden Enantiomere von 2a‐2d besitzen S‐Konfiguration. ‐ Die Prüfung von Ratten ergab. daß alle synthetisierten zyklischen Harnstoffe sedativ‐hypnotische Wirksamkeit besitzen. Die Enantiomere wiesen zum Teil beachtliche enantioselektive Wirkungsunterschiede auf.
Synthesis and Platelet Aggregation Inhibiting Activity of Acid Side‐chain Modified Hydantoin Prostaglandin Analogues
Authors: Barraclough Paul , Caldwell A. Gordon , Glen Robert C. , Harris C. John , Stepney Ray , Whittaker Norman , Whittle Brendan J. R.
Published: October 2006

A series of hydantoin prostaglandin analogues, in which the hexamethylene moiety of the acid side chain was replaced by other spacing groups possessing either ether, sulphide and/or olefin functionality, were prepared and evaluated for platelet aggregation inhibiting activity. The 4‐thia analogue 13 proved to be the most potent inhibitor (ca. 22x PGE1) and the 3‐thia‐ and 3‐oxa‐analogues, 6 and 10 respectively, are approximately equipotent with BW245C (ca. 14x PGE1). Z‐olefinic analogues (e.g. 11) were usually more potent than their E‐isomers (e.g. 12). Structure‐activity relationships are discussed in detail.
Synthesis of the Naphthalenic Bioisostere of Indorenate. Synthese des Naphthalin‐Bioisosters von Indorenat
Authors: Yous Said , Depreux Patrick , Renard Pierre
Published: October 2006

The relationships between some physiological processes and central nervous system or peripheral activity of serotonin (5‐HT; A) has resulted in extensive studies of the chemistry and biological properties of many serotoninergic (agonists or antagonists) compounds1) and the existence of multiple serotoninergic receptors subtypes is supported by pharmacological evidence2). So, central 5‐HT binding sites can be classified into 5‐HT1 (1A, 1B, 1C, 1D), 5‐HT2, 5‐HT3 and 5‐HT4 subtypes3,4) There is some basis for considering that central serotoninergic agonists might be antihypertensives acting via 5‐HT1A receptors5,6,7) Indorenate (B), a synthetic indole. closely related to serotonin, has antihypertensive properties resulting from agonist activity at central serotoninergic receptors with a relatively high affinity for 5‐HT1A sites8).

A possible approach in the design of new serotoninergic ligands and more generally new drug candidates may consist in the application of the bioisosteric theory. So, the NH group is a classical bioisostere of the vinyl increment and the naphthalene nacleus could be considered as a bioisostere of the indole ring. Few examples of the naphthalene‐indole bioisosterism have emerged in the lit.9,10,11) Here we describe the synthesis of the naphthalenic bioisostere C of B (Scheme 1).
Histamine Analogues, XXXV: 2‐Substituted Histamine Derivatives Containing Classical Moieties of H2‐Antagonists ‐ a Novel Class of H1‐Agonists
Authors: Zingel Volkmar , Elz Sigurd , Schunack Walter
Published: October 2006

A new type of H1‐agonists resulted from the combination of the essential histamine structure with parts of H2‐antagonists. 2,4‐Disubstituted imidazole derivatives were synthesized by reaction of imidic acid methyl esters with 1,3‐dihydroxypropanone, 1,4‐dihydroxybutanone or 2‐oxo‐4‐phthalimido‐1‐butylacetate in liquid NH3. The imidazole intermediates were converted into histamine analogues by simple deprotection, Gabriel synthesis followed by deprotection, or by side‐chain elongation via the nitriles and final hydrogenation. The new compounds were screened for H1‐activity on the isolated guinea‐pig ileum and for H2‐antagonistic activity on the isolated guinea‐pig right atrium. The substances are comparably weak H1‐agonists and moderate H2‐blockers.
Darstellung von Phosphonsäurealkylesteramiden als strukturelle Analoga von Sulfadimidin und Acetophenetidin
Authors: Buseck Stephan , Neidlein Richard
Published: October 2006

Die Phosphonsäurealkylesteramide 19 und 36 wurden als strukturelle Analoga von Sulfadimidin und Acetophenetidin dargestellt. 19 wurde nicht durch nukleophile aromatische Substitution erhalten, war jedoch zugänglich durch katalytische Hydrierung des entspr. Nitroderivats. Kondensation von 13 mit aromatischen Aldehyden und nachfolgende Reduktionen lieferte die Amine 26‐28.
Nitroketenaminale, 9. Mitt.: Zur Umsetzung von α,β‐ungesättigten Aldehyden mit Nitroketenaminalen
Authors: Troschütz Reinhard , Lückel Achim
Published: October 2006

Die Umsetzung der α,β‐ungesättigten Aldehyde 1a,b mit dem Nitroketenaminal 2a führt in siedendem Eisessig zu den C‐6 unsubstituierten 2‐Amino‐3‐nitropyridinen vom Typ 4. Durch Erhitzen in Alkohol/Eisessig bzw. in Alkoholen entstehen aus 1a und 2a die 2‐Alkoxy‐1,2,3,4‐tetrahydropyridine 7a und 8a. Aus 1a und 2b bilden sich analog die 5‐Alkoxy‐2,3,4,5,6,7‐hexahydroimidazo[1,2‐a]pyridine 7b bzw. 8b. Über 1H‐NMR‐Daten kann die relative Konfiguration von 7aC, 7aT, 7bC und 7bT ermittelt werden.
Platelet Aggregation Inhibiting and Anticoagulant Effects of Oligoamines, XX: 4,4′,4″‐(1,3,5)‐Benzene‐tris‐sydnone Imines
Authors: Rehse Klaus , Martens Antje
Published: October 2006

The synthesis of ten tris‐sydnone imine derivatives, unknown up to now, is described. All compounds are alkyl or arylalkyl substituted in 3‐position of the sydnone imine. The most powerful agent was the 3‐propyl derivative 6c. It inhibits the aggregation of human platelets induced by collagen in a concentration of 1 γmol/L half maximally. Its N‐ethoxycarbonyl derivative 7c, which was designed as a prodrug, showed only small antithrombotic effects in rats. The reason for this low degree of activity is discussed.
Compounds with Positive Inotropic Activity, IV: Synthesis of N‐Methoxyquinolinium Salts and Their Effects in Heart Muscles
Authors: Bünz Claudia , Heber Dieter , Ravens Ursula
Published: October 2006

N‐Methoxyquinolinium salts 3 are prepared as potential cardiotonic agents by alkylation of the corresponding N‐oxides 2 synthesized by two different methods. 1. Oxidation of some quinoline derivatives 1 using 30% H2O2 or 3‐chloroperbenzoic acid. 2. Nitration of the quinoline‐N‐oxides 2a, 2c, and 2m. Preparation of 2h and 2k requires subsequent nucleophilic ipso‐substitution of the nitro group. The compounds 3 are tested for positive inotropic activity on isolated left atria and papillary muscles from guinea‐pig. Structure activity relationships indicate that the effect depends on the N‐methoxy group of the target compounds as well as on the presence of an electron‐withdrawing substituent.
Protonierung von α‐Keto‐enaminen
Authors: Kuckländer Uwe , Schneider Bettina
Published: October 2006

Bei den Cyclopentenon‐ und Cyclohexenon‐Abkömmlingen 2 und 6b wird in CDCl3/CF3COOH Protonierung mit nachfolgender Enolisierung nachgewiesen. Das Cyclohexenon‐Derivat 6a wird am Heteroatom, das Cycloheptenon‐Derivat 10 sowohl am Heteroatom als auch an C‐3 protoniert. Als Ursache für die unterschiedliche Protonierung werden sterische Behinderung der Coplanarität und thermodynamische Gründe auf der Grundlage von MNDO‐ und AM1‐Berechnungen angegeben.
Morphine Alkaloids, CXVII: Investigation of the Azidolysis of Tertiary Alcohols of Thebaine Derivatives with Bridged Ring C
Authors: Sepsi Ágnes , Berényi Sándor , Makleit Sándor , Tóth Zoltán
Published: October 2006

Replacement of the C‐19 tertiary hydroxyl group of some thebaine and oripavine derivatives with bridged ring C (so‐called Bentley's compounds) for an azido group has been performed with hydrazoic acid. In case the hydroxyl group was connected to a centre of chirality, substitution resulted in the formation of diastereomeric mixture of azides and elimination took place as well, the extent of which was dependent mainly on steric factors. Configuration of the C‐19 has been determined by 1H‐NMR spectra and calculated proton‐proton distances of amines 13a and 13b obtained by the reduction of 10c followed by separation.
Synthese potentieller Squalenepoxidase‐Hemmer mit konformativer Fixierung der Strukturelemente des Butenafins
Authors: Stanetty Peter , Wallner Herbert
Published: October 2006

Es wird über die Synthese der Naphthalinmethanamine 6b‐h berichtet, bei denen zur konformativen Fixierung Substituenten mit zunehmendem Raumerbedarf in die α‐Position eingeführt wurden. Da die reduktive Aminierung der Naphthylalkanone 3 mit den Aminen 9 bzw. 10 nun sehr beschränkt einsetzbar war, wurden als geeignete Zwischenprodukte zunächst α‐substituierte Naphthalinmethanamine 2 und 4 auf verschiedenen Wegen synthetisiert und erst anschließend das angestrebte N‐Substitutionsmuster der Zielverbindungen durch geeignete ‐ meist reduktive ‐ Alkylierungsmethoden aufgebaut.
Synthese neuer 7‐Benzofuranmethanamine als heterocyclische Analoga des Squalenepoxidasehemmers Butenafine
Authors: Stanetty Peter , Koller Herbert , Pürstinger Gerhard , Grubner Silvia
Published: October 2006

Ausgewählte Titelverbindungen (6a‐f, 7a‐d) wurden aus entspr. (2,3‐Dihydro‐)7‐Benzofurancarbonsäuren 1a‐f bzw. 2a‐d durch RedAlR‐Reduktion der Carboxamide 4a‐f und 5a‐d aufgebaut. Aus praktischen Erwägungen wurde für die Darstellung der 2,3‐Dihydro‐2‐methyl‐7‐benzofuranmethanamine 6h‐k mit variiertem N‐Substitutionsmuster die Alkylierung des N‐Methyl‐benzofuranmethanamins 6g mit den vorgefertigten Aralkylbromiden 9a‐d bevorzugt.
Ketomethylenebestatin: Synthesis and Aminopeptidase Inhibition
Authors: Herranz Rosario , Castro‐Pichel Julia , García‐López M. Teresa , Gómez‐Monterrey Isabel , Pérez Concepción , Vinuesa Soledad
Published: October 2006

The synthesis of (6R,5S,2RS)‐6‐amino‐5‐hydroxy‐2‐isobutyl‐4‐oxo‐7‐phenylheptanoic acid (9), a carbaanalogue of the aminopeptidase (AP) inhibitor bestatin (1) is described. This synthesis was carried out by a malonic ester alkylation with the suitably protected halomethyl ketone of (2S,3R)‐AHPBA.
Peroxide als Pflanzeninhaltsstoffe, 12. Mitt.: Peroxide vom Davanon‐Typ aus der Eberraute (Artemisia abrotanum) und ihre Darstellung
Authors: Rücker Gerhard , Manns Detlef , Wilbert Sibylle
Published: October 2006

Aus den oberirdischen Teilen der Eberraute (Artemisia abrotanum L., Asteraceae) wurden neben (+)‐Davanon (1) und Arteinculton (3) die bekannten Peroxyhalbketale 2, 5 und 7 isoliert. Als neue Peroxide vom Davanon‐Typ konnten Epi‐Arteinculton (4) und Spiro‐Arteinculton (6) durch dc Vergleich in der Pflanze nachgewiesen werden. Bei der Singulett‐Sauerstoff‐Oxidation von 1 werden 2, 3, 4, 5und 7 gebildet, bei der Triplett‐Sauerstoff‐Oxidation 2, 3, 5, 6, 7 und Hydroxy‐Davanon.
Antimykotische Wirkstoffe, 20. Mitt.: Bioisostere 6‐Arylpyrimidin‐Derivate
Authors: Kreutzberger Alfred , Burger Angelika
Published: October 2006

Durch Kondensation vonN‐(2‐Hydroxyethyl)‐N‐methylguanidinsulfat (1) mit den 1‐Aryl‐substituierten β‐Diketonen4a‐eerhält man die bioisosteren 2‐[(2‐Hydroxyethyl)‐methylamino]‐6‐arylpyrimidine5a‐e. Die Verbindungen5a‐cbesitzen signifikante antimykotischein vitro‐ undin vivo‐Aktivitäten.
Conformational Studies of Hexahydro‐benzo[c]phenanthridine Alkaloids: Solid and Solution Conformations of Deoxycorynoline
Authors: Kamigauchi Miyoko , Miyamoto Yuko , Iwasa Kinuko , Takao Narao , Ishida Toshimasa , In Yasuko , Inoue Masatoshi
Published: October 2006

The conformation of (±)‐deoxycorynoline (4), which was derived from (±)‐corynoline (1), was investigated by X‐ray crystallographic analysis. The crystal structure of (±)‐4 exists in B/C „anti‐cis”︁ conjunction, half‐chair of ring B and twist‐half‐chair of ring C, and shows the same conformation as that of the parent alkaloid (±)‐1. Conformational analyses of CD spectra in solution suggested that (+)‐4, derived from (+)‐1, has essentially the same conformation as in the crystal state of (±)‐4. The CD spectrum of (+)‐4 shows a slight temp.‐dependence, whereas that of (+)‐1 shows no dependency under the same conditions.
Carvedilol Stereopharmacokinetics in Rats: Affinities to Blood Constituents and Tissues
Authors: Stahl Elke , Mutschler Ernst , Baumgartner Ulrich , Spahn‐Langguth Hildegard
Published: October 2006

Carvedilol, a lipophilic β‐adrenoceptor antagonist with vasodilating activities, is characterized by a high as well as stereoselective metabolic clearance and distribution volume. Tissue distribution of carvedilol enantiomers and their conjugates were determined under steady‐state conditions in rats (p.o., 10 mg/kg, repetitive dosage; n = 5) and after single i.v. administration in control rats and rats with surgical portacaval shunt (pcs) (10 mg/kg; n = 3 each group). In addition, in vitro plasma protein binding was evaluated. ‐ The plasma protein binding of carvedilol in rats is > 98% for total plasma (tp) and > 96% for rat serum albumin (rsa) solution (4%), with enantioselectivity ratios of 1.53 (tp) and 1.27 (rsa). Significantly higher unbound fractions were observed in pcs rats, in part due to reduced protein concentrations. ‐ In contrast to plasma, where a preponderance of the R‐enantiomer with an S/R ratio of 0.6 was found, S‐carvedilol was predominant in all tissues (heart, liver, kidneys, lung, spleen, muscle, and adipose tissue), with S/R ratios of 1.3‐1.4 in most of these tissues and 2.3 in liver. This preferential tissue partitioning of S‐carvedilol was in accordance with its higher unbound fraction in plasma. Carvedilol accumulated predominantly in the highly perfused and/or eliminating organs liver, kidneys, and lung (tissue/plasma ratios; lung: S 76, R 34; liver: S 21, R 5; kidney: S 8, R 3). A similarly enantioselective distribution into the heart of control as well as pcs rats was observed, where the S‐enantiomer concentrations exceeded the plasma concentrations 7‐fold. Probably because of the impaired liver function in pcs rats with increased importance of the renal route, kidney concentrations were higher in these rats. The kidney/plasma ratio was elevated approximately 2‐fold for the parent compound (control: S 7, R 2; pcs: S 14, R 4) and 4‐fold for the R‐carvedilol conjugate (control: S 2, R 1; pcs: S 3, R 4).

The conjugates of carvedilol were detectable in all organs, with significantly smaller concentrations than those of the aglycones and with varying stereoselectivities.
New NO‐Donors with Antithrombotic and Vasodilating Activities, II: 3‐Alkyl‐N‐nitroso‐5‐sydnone Imines
Authors: Rehse Klaus , Schleifer Klaus‐Jürgen , Ciborski Thomas , Bohn Helmut
Published: October 2006

Fifteen 3‐alkyl‐, four 3‐cycloalkyl‐N‐nitroso‐5‐sydnone imines and five 3‐alkyl‐N‐nitro‐5‐sydnone imines were synthesized and their ability to inhibit platelet aggregation induced by collagen (Born‐test) was studied in vitro. Dependent on the chemical structure, the IC50‐values for the inhibition of platelet aggregation were in the range of 0.2‐140 μmol/L. It is suggested that this scale reflects different binding properties of the nitrosimines with respect to the platelet membrane. Highest activities were observed for the 3‐hexyl (2f) and the 3‐cyclohexyl (2p) derivative. Three nitrimines (3e, 3f, 3i) also showed IC50 values below 10 μmol/L. For the nitrosimines 2a, 2f, and 2m antithrombotic activity was demonstrated in vivo. They inhibited laser induced arterial thrombosis in anesthetized rats up to 70% two h after oral administration. In conscious renal‐hypertensive dogs, the decrease in systolic blood pressure and left ventricular enddiastolic pressure suggests an antianginal activity of the compound 2a similar to that of molsidomine (M). The smoother onset and the longer duration of action of the new compound as compared to M could be a significant advantage of 2a in the therapy of angina pectoris.
Effects of Oxygen Radicals, Hydrogen Peroxide and Water‐soluble Singlet Oxygen Carriers on 5‐ and 12‐Lipoxygenase
Authors: Müller Klaus , Ziereis Klaus
Published: October 2006

Inhibition of 5‐lipoxygenase from bovine polymorphonuclear leukocytes and 12‐lipoxygenase from bovine platelets by active oxygen species has been studied. Oxygen radicals and hydrogen peroxide markedly inhibited 12‐lipoxygenase, whereas 5‐lipoxygenase activity was only moderately influenced. Singlet oxygen liberated from water‐soluble naphthalene endoperoxides was without effect.
New 4‐Amino‐7,8‐dimethoxy‐5h‐pyrimido[5,4‐b]indole Derivatives: Synthesis and Studies as Inhibitors of Phosphodiesterases
Authors: Monge Antonio , Martínez‐Crespo Francisco J. , Villanueva M. Aránzazu , Font María , Santiago Esteban , Mart Juan J. , de Irujo Ínez , Alberdi Elena , López‐Unzu M. José , Cenarruzabeitia Edurne , Castiella Elena , Frechillac Diana
Published: October 2006

A series of 4‐amino‐7,8‐dimethoxy‐5h‐pyrimido[5,4‐b]indole derivatives has been synthesized. These compounds resemble carbazeram and other pyridazino compounds with activity in the cardiovascular system. Some of these new compounds possess inotropic activity (Table 2), with a complementary effect on the inhibition of different CGI‐PDE (Table 3). The most active compounds 5, 6d, and 7 also possess activity as vasodilators (Table 4). Some of these new compounds inhibit blood platelet aggregation induced by ADP and AA and are active as inhibitors of human platelet PDEs (Tables 5 and 6).
Cyclic Analogs of Chemotactic Formylpeptides, I.: Synthesis and Biological Activity of For‐Cys‐Leu‐Phe‐Cys‐OMe
Authors: Zecchini Giampiero Pagani , Paradisi Mario Paglialunga , Torrini Ines , Lucente Gino , Traniello Serena , Spisani Susanna
Published: October 2006

By using the side chain to side chain mode of cyclization the 14‐membered disulfide cyclopeptide (5) has been synthesized as conformationally constrained analog of the prototypical chemotactic tripeptide For‐Met‐Leu‐Phe‐OMe. Compound 5 is inactive towards human neutrophils. The lack of biological activity of cyclotetrapeptide 5 is discussed taking into account the backbone folding and the side chain topography.
1‐Aryl‐2‐amino/hydrazino‐4‐phenyl‐1,6‐dihydro‐1,3,5‐triazine‐6‐thione and Related Thiocarbamides/Thiosemicarbazides as Antithyroidal Agents
Authors: Prasad R. , Srivastava P. K.
Published: October 2006

Different 1‐aryl‐2‐benzylmercapto‐4‐phenyl‐1,6‐dihydro‐1,3,5‐triazine‐6‐thiones have been synthesized by known methods. These triazines on treatment with ammonia/hydrazine hydrate afforded the corresponding 1‐aryl‐2‐amino/hydrazino‐4‐phenyl‐1,6‐dihydro‐1,3,5‐triazine‐6‐thiones which on treatment with arylisothiocyanates afforded the related thiocarbamides/thiosemicarbazides. Some of these compounds show appreciable antithyroidal activity.
Aqua[1‐(2,6‐dichloro‐4‐hydroxyphenyl)‐2‐phenylethylenediamine]sulfatoplatinum(II) Complexes with Variable Substituents in the 2‐Phenyl Ring, II: Correlation of Molecular Structure and Estrogenic Activity of Breast and Prostate Cancer Inhibiting [erythro‐1‐(2,6‐Dichloro‐4‐hydroxyphenyl)‐2‐(2‐halo‐4‐hydroxyphenyl)ethylenediamine]platinum(II) Complexes
Authors: Gust Ronald , Schönenberger Helmut , Klement Ulrich , Range Klaus‐Jürgen
Published: October 2006

Complete three‐dimensional X‐ray crystal structure analyses of estrogenic [erythro‐1‐(2,6‐dichloro‐4‐hydroxyphenyl)‐2‐(2‐halo‐4‐hydroxyphenyl)ethylenediamine]diiodoplatinum(II) complexes (halo = fluoro:erythro 8‐Ptl2 and halo = chloro:erythro‐9‐PtI2) which were synthesized for application in breast and prostate cancer, have been carried out. 6239 as well as 6521 reflexes were measured and refined to an R‐value of 0.105 and 0.066, respectively. The molecules of erythro‐8‐PtI2 are displaced laterally from a possible Pt‐Pt‐axis separated, alternatingly, by Pt‐Pt‐distances of 3.62 Å and 6.27 Å. A comparable structure possesses erythro‐9‐PtI2 with Pt‐Pt‐distances of 3.59 Å and 6.32 Å.

The ethylenediamine ligands of erythro‐8‐PtI2 and erythro‐9‐PtI2 are puckered and exist in half chair conformations. For both complexes the 2,6‐dichloro‐4‐hydroxyphenyl ring is equatorially arranged, while the 2‐halo‐4‐hydroxyphenyl ring is nearly perpendicular to the N‐Pt‐N plane. The O‐O‐distance between the phenolic oxygens amounts to 8.1 Å in erythro‐8‐PtI2 and to 7.8 Å in erythro‐9‐PtI2. Though these O‐O‐distances differ strongly from that (12.1 Å), which is considered to be necessary for the binding of an estrogen to its receptor, [1‐(2,6‐dichloro‐4‐hydroxyphenyl)‐2‐(2‐halo‐4‐hydroxyphenyl)ethylenediamine)]platinum(II) complexes show estrogenic effects which are, however, strongly reduced compared to that of therapeutically used estrogens like diethylstilbestrol. The relationship between molecular structure and estrogenicity as well as the significance of the latter for antitumor activity and untoward side effects are thoroughly discussed.
Frankfurt Shift, 2. Mitt.: Weitere Beiträge zur intramolekularen Umlagerung von N‐Oxiden tertiärer Cycloalkylamine zu Lactamen (Frankfurt Shift)
Authors: Oelschläger Herbert , Schmidt Wolfgang
Published: October 2006

Die grundlegenden Kenntnisse über den Frankfurt Shift wurden erweitert durch Untersuchungen über den kinetischen Isotopieeffekt, ein Kontrollexperiment mit 18O2‐Atmosphäre und einen Shift‐Versuch mit 1‐(4‐Fluorbenzyl)‐piperidin‐N‐oxid (4). Außerdem konnte der Shift erstmalig auch im Ganztierversuch (Ratte) nachgewiesen werden.
Antineoplastic and Antiviral Activities of Podophyllotoxin Related Lignans
Authors: Gordaliza Marina , Castro María A. , García‐Grávalos María D. , Ruiz Pilar , Del Corral José M. Miguel , Feliciano Arturo San
Published: October 2006

28 cyclolignans, most of them derived from podophyllotoxin, have been evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P‐388 murine leukemia, A‐549 human lung carcinoma, and HT‐29 colon carcinoma, while antiviral assays were performed on herpes simplex virus type I infecting fibroblasts of monkey kidney (HSV/CV‐1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both groups of assays at concentrations below 1μM; deoxypodophyllotoxin (1) being the most potent compound in all cases.
Synthese und kombinierte H1‐/H2‐antagonistische Aktivität von Mepyramin‐, Pheniramin‐ und Cyclizin‐Derivaten mit Cyanoguanidin‐, Harnstoff‐ und Nitroethendiamin‐Partialstrukturen
Authors: Schulze Frank R. , Alisch Rudi A. , Buschauer Armin , Schunack Walter
Published: October 2006

Durch die Verknüpfung typischer Partialstrukturen von H1 und H2‐Antagonisten über eine Cyanoguanidin‐, Harnstoff‐ oder Nitroethendiamin‐gruppe wurden Substanzen mit kombinierter H1‐/H2‐antihistaminischer Wirkung synthetisiert. Der Verlust des basischen Seitenketten‐Stickstoffs führt am H1‐Rezeptor des Meerschweinchenileums zu einem Abfall der Aktivität im Vergleich zu den betreffenden Referenzsubstanzen mit gleicher H1‐Partialstruktur. Am Meerschweinchenatrium (H2‐Rezeptormodell) erwiesen sich Verbindungen mit Mepyramin‐ und Cyclizinstrukturelement im Vergleich zu den Referenz‐H2‐Antagonisten (Tiotidin, Ranitidin, Lamtidin) ebenfalls als schwächer wirksam. Dagegen führt die Verknüpfung mit einem Pheniraminbaustein zu stark wirksamen H2‐Antagonisten, die bis zu 27fache Cimetidinaktivität erreichen.
Untersuchungen an 1,4‐Naphthochinonen, 23. Mitt.1): 2/3‐Halogen‐2/3‐nitrophenyljuglonderivate, Synthese und cytotoxische Eigenschaften
Authors: Wurm Gotthard , Gurka Hans‐Joachim
Published: October 2006

1,4‐Naphthochinonderivate lassen sich durch oxidative Decarboxylierung von 2‐ und 4‐Nitrobenzoesäure radikalisch arylieren. Ausgehend von 2‐ bzw. 3‐Halogenjuglonderivaten entstehen die 4‐Nitrophenylverbindungen 10–13 in guten, die 2‐Nitroanalogen 14–17 in geringen Ausb. Alle Verbindungen sind unwirksam gegen Viren vom Typ HSV und HIV, ihre z.T. ausgeprägte Cytotoxizität ist abhängig vom Substitutionsmuster. Die 3‐Aryl‐ und o‐Nitroderivate sind aktiver als die analogen 2‐Aryl‐ und p‐Nitroverbindungen. Der Einfluß der Brom‐ bzw. Chlorsubstitution ist nur bei dem Verbindungspaar 12/13 bemerkenswert.
Proton Acid‐Catalysed Transformations of Estrogen Derivatives: New Results and Some Mechanistic Aspects of the Kober Colour Reaction
Authors: Pindur Ulf , Schall Thomas
Published: October 2006

The 3‐O‐methylated estrogen derivatives 1a‐d and α‐estradiol (1e) underwent sulfuric acid‐catalysed transformations to furnish the steroids 2–6. The processes involved in the reaction sequence are regioselective sulfonation and, above all, the Wagner‐Meerwein rearrangement of the methyl group at C‐13. With the objective of obtaining further information on the course of the Kober colour reaction of estrogens, some UV/VIS and ESR spectroscopic investigations were also carried out.
New NO‐Donors with Antithrombotic and Vasodilating Activities, VII: Z/E‐Isomerism in Thiazole‐ and 1,3,4‐Thiadiazole‐2‐nitrosimines
Authors: Rehse Klaus , Lüdtke Eberhard
Published: October 2006

In thiazole‐ (23 compounds) and 1,3,4‐thiadiazole‐2‐nitrosimines (20 compounds) Z/E‐isomers were described by 1H‐NMR‐spectroscopy. There is a mutual conversion of the isomers. The coalescence temp. (Tc) mostly is 310 K. In the thiazole series, however, for five compounds higher energy barriers are observed. This is due to substituents in 4‐position with electron withdrawing properties. The Tc is increased when the compounds are dissolved in water instead of DMSO. Hereby it is concluded that the isomers have Ze or Ee configuration. It is made probable that the low field signal for the substituent in 3‐position corresponds to the Ze‐isomer, which has a slight preference. The free enthalpy of rotation, calculated approximately, is between 56.0 (1m) and 73.7 kJ/mol (1r).
Synthesis and Biological Evaluation of Some Potential Antimalarials. Synthese und biologische Bewertung einiger potentieller Wirkstoffe gegen Malaria
Authors: Tsai Chang Swei , Shen Ai Yu
Published: October 2006

Malaria chemotherapy has been well reviewed. Malarial parasites gaining resistance is the major problem in the treatment of the disease. Some strains are resistant not only to chloroquine but also to amodiaquine. Few new drugs are available or foreseen for the near future. The principal metabolite of cinchona alkaloids appears to be oxidized at C‐2. This may result in a loss of activity. Pinder and Burger suggested that a trifluoromethyl group will prevent this oxidation. So 2‐tribromomethyl‐6‐methoxy‐4‐(4‐hydroxy‐3‐pyrrolidinomethylanilino)quinoline (I) was synthesized as a potential biocide (Scheme 1).
Complexation of Hydrocortison with β‐Cyclodextrin and Hydroxypropyl‐β‐Cyclodextrin
Authors: Preiss Andrea , Mehnert Wolfgang , Frömming Karl‐Heinz
Published: October 2006

Hydrocortison (HC) forms water‐soluble inclusion compounds with β‐cyclodextrin (βCD) and hydroxypropyl‐β‐cyclodextrin (HPβCD), as proved by the equilibrium phase solubility diagrams and by 1H‐NMR spectroscopy. The solubility isotherm of the HC/βCD system is of the BS type, that of the HPβCD system of the AL type. The values of the complex stability constants are K = 4792 M−1 and 1739 M−1, respectively. 8 parallel preparations of solid HC/βCD complexes by coprecipitation resulted in a stoichiometric ratio of 0.49:1 which corresponds to a molar ratio of 1:2; the HC content is 13.2±0.2%. The ratio of the HC/HPßCD complex is 0.335 which equals a molar ratio of 1:3; the HC content is 8.6 ± 0.2%. The proof of inclusion formation was performed by X‐ray diffractometry and thermoanalytical procedures (DSC, TG, thermofractography). We cannot exclude that some of the HC molecules are not included in the HPßCD cavity.
Isochromanylpenicilline
Authors: Unterhalt Bernard , Nocon Birgit , Krebs Bernt , Läge Mechthild
Published: October 2006

(R/S)‐Isochroman‐1‐carbonsäure (1) wird in ihre Enantiomere gespalten und ebenso wie diese mit 6‐Aminopenicillansäure zu den Titelverbindungen 2 umgesetzt. Die Wirkung der neuen Penicilline gegenüber grampositiven und gramnegativen Bakterien wird mit der von Benzylpenicillin verglichen.
Zur Reaktion von 3,5‐Bis(methylthio)‐1,2‐dithiolium‐Salzen mit CH‐aciden Verbindungen
Authors: Popp Xue‐Ping , Hartke Klaus
Published: October 2006

Die 3,5‐Bis(methylthio)‐1,2‐dithiolium‐tetrafluoroborate3a‐ckondensieren in Gegenwart von Ethyl‐diisopropylamin mit Malondinitril zu den Thiophenen9a‐c, mit Cyanessigsäuremethylester zu den Thiophenen9d‐fsowie zu den 3‐Alkyliden‐1,2‐dithiolen10a‐cund mit Nitromethan zu den Thiophenen9g, 12sowie dem 3‐Alkyliden‐1,2‐dithiol10d. Die Selbstkondensation von3aergibt das Trithiapentalen13und das Isotrithiapentalen14.
New NO‐Donors with Antithrombotic and Vasodilating Activities, IX: Thiadiazole Nitrosimines
Authors: Rehse Klaus , Lüdtke Eberhard
Published: October 2006

Twenty 1,3,4‐thiadiazole‐2‐nitrosimines and two 1,2,4‐thiadiazole‐5‐nitrosimines were synthesized and assayed in the Born‐test for their antiplatelet activity. Only two 1,3,4‐thiadiazoles inhibited the aggregation at IC50 < 10 μmol/L. In an in vivo thrombosis model only in arterioles a small inhibition of thrombus formation was observed. The poor test results correspond to a very high chemical stability of the titel nitrosimines.
Zur Acetylierung von Spironolacton, Canrenon und 2‐Methylencanrenon
Authors: Görlitzer Klaus , Moormann Peter , Pollow Kunhard , Schaffrath Michael
Published: October 2006

Bei der Umsetzung der Titelverbindungen mit Acetanhydrid und Acetylchlorid werden das 3,5‐Dien‐3‐yl‐acetat 2, die isomeren 2,4,6‐ und 3,5,7‐Trien‐3‐yl‐acetate 3 und 4 sowie das 2,4,6,8(14)‐Tetraen‐3‐yl‐acetat 7 erhalten. Hydrolyse von 7 liefert das 2α‐Methl‐8,14‐didehydro‐canrenon (9). 7 und 9 wurden auf ihre Bindungsfähigkeit gegenüber Hormon‐Rezeptoren sowie den Serumproteinen SHBG und CBG geprüft: Die Substanzen erwiesen sich als inaktiv.
Untersuchungen an 1,4‐Napthochinonen, 24. Mitt.: Zur Dehalogenierung von 2‐/3‐Halogen‐1,4‐naphthochinon‐derivaten
Authors: Wurm Gotthard , Duchstein Hans‐Jürgen
Published: October 2006

Während Bu3SnH ein effektives Reagenz zur Debromierung von 2‐Bromnaphthochinonen ist, erfolgt Cl‐Eliminierung bei Einsatz von 1c nur zu 30%. Mit Et3SiH ist überhaupt keine Dechlorierung zu erreichen, dafür entsehen mit den 5‐Acetoxyderivaten 1a/1d als Startkomponenten die cyclischen Acetale 3a–c als selektiv geschützte Juglonderivate. Die Bromverbindung 3a entsteht nur bei Temp. unterhalb 10°, bereits bei Raumptemp. tritt Br‐Eliminierung ein, wobei 3b aber nur in geringer Ausb. anfällt. Ein besonders geeignetes Reagenz zur Debromierung und damit Gewinnung der Naturstoffe Plumbagin (2a) und Isoplumbagin (2b) aus den Bromderivaten 1a–b ist Zink‐Silber‐Paar, Cl‐Eliminierung erfolgt aber wieder nur in Spuren.
Synthesis of the First Penicillin Derivatives with Medium‐Sized Lactam Ring and of Related Thiazolidines
Authors: Imming Peter
Published: October 2006

The novel concept of penicillin derivatives 4 with a medium‐sized instead of a β‐lactam ring is presented. Two synthetic paths were invented, resulting in the evaluation of the synthetic potential in the succinic, glutaric, and adipic acid series. A number of novel penicillin‐derived thiazolidines were prepared, notably the derivatives 16 and 22 with anellated 7‐ and 13‐membered lactam ring.