Showing papers in "Archiv Der Pharmazie in 1992"

Reduction of amidoxime derivatives to pentamidine in vivo.

Abstract: In vivo Reduktion von Amidoximderivaten zu Pentamidin

Synthese von 7,12‐Dihydro‐indolo[3,2‐d][1]benzazepin‐6‐(5H)‐onen und 6,11‐Dihydro‐thieno‐[3′,2′:2,3]azepino[4,5‐b]indol‐5(4H)‐on

Abstract: Die Titelverbindungen 4 und 6 wurden durch Fischer-Indol-Synthese dargestellt. 4a wird durch Brom in Eisessig in 10-Position substituiert. 4 und 6 zeigen eine schnelle Ringinversion des Azepinringes. Synthesis of 7,12-Dihydro-indolo[3,2-d][1]benzazepin-6-(5H)-ones and 6,11-Dihydro-thieno-[3′,2′:2,3]azepino[4,5-b]indol-5(4H)-one The title compounds 4 and 6 were prepared by Fischer indole synthesis. 4a is substituted in 10-position by reaction with bromine in glacial acetic acid. A fast ring inversion is observed for the azepine ring in 4 and 6.

Synthesis of novel thieno[2,3-d]pyrimidine, thieno[2,3-b]pyridine and thiazolo[3,2-a]thieno[2,3-d]pyrimidine derivatives and their effect on the production of mycotoxins.

Abstract: The thiophene derivative 1 reacts with the active methylene reagents 2a-c to afford the thieno[2,3-d]pyrimidine derivatives 6a,b and 8, respectively. 1 reacts with phenacyl bromide 2d to afford the N-alkylation product 9 and reacts with phenacyl thiocyanate 2e to afford the N-(thiazol-2-yl) derivative 10, which was further cyclized into thiazolo[3,2-a]thieno[2,3-d]pyrimidine derivative 12. Compound 1 reacts also with the cinnamonitriles 3a,b to afford the thieno[2,3-b]pyridines 15a,b, respectively. 1 undergoes either acetylation or hydrolysis to afford the thieno[2,3-b]pyridine derivative 19 and the thiophene derivative 22, respectively. Some of the new compounds show inhibitory effect to the production of mycotoxins and to fungal growth.

Synthese und Stereochemie potentiell stark analgetischer 2,4‐m‐diarylsubstituierter 3,7‐Diazabicyclo[3.3.1]nonan‐9‐on‐1,5‐diester

Abstract: Der 2,4-di-2-pyridylsubstituierte 7-Methyl-3,7-diazabicyclo[3.3.1]nonan-9-on-1,5-diester zeigt am vas deferens der Maus befriedigende K-agonistische Aktivitat. - Zur Verstarkung der analgetischen Wirksamkeit werden Derivate mit m-OH-, m-OCH3-, m-Cl-, m-CH3- und m-NO2-Substituierten Phenylresten an C-2/4 synthetisiert: Aus entspr. Benzaldehyden, Methylamin und Oxoglutarsaureester werden Piperidonisomerengemische erhalten, die aus cis-Keton und -Enol sowie trans-Enol bestehen; deren Isomerisierungsverhalten wird in CDCl3 und CD3OD untersucht. Aus diesen Piperidonen werden durch Kondensation mit HCHO und Methylamin die Bicyclen erhalten, die eine verhaltnismasig starre Struktur durch eine gehinderte Rotation der Arylreste um die C-2- bzw. C-4-Arylachse (ΔG* ca. 18 kcal/mol) besitzen. Synthesis and Stereochemistry of Potential Opioid-like 2,4-m-diarylsubstituted 3,7-Diazabicyclo[3.3.1]nonan-9-one-1,5-diesters The 2,4-di-2-pyridyl- substituted 7-methyl-3,7-diazabicyclo[3.3.1]nonan-9-one-1,5-diester shows a reasonable K-agonistic activity in the mouse vas deferens test. - To enhance the analgetic activity derivatives with m-Cl-, m-CH3-, m-OCH3-, m-OH-, and m-NO2 substituted phenyl residues at C-2/4 were synthesized: From the condensation of benzaldehydes, methylamine, and oxoglutarate isomeric mixtures of piperidones were obtained, containing cis-ketone and -enol and trans-enol; the isomerisation reactions of these piperidones were observed in CDCl3 and CD3OD. The bicyclus resulting from the reaction of the piperidones with HCHO and methylamine exhibits conformational rigidity because the free rotation of the 2,4-aryl groups is hindered. The rotational barrier around the C-2-aryl-bond was shown to be 18 kcal/mol by analysis of variable temp. 1H-NMR spectra.

Kurzmitteilungen: Passiflora and Lime‐blossoms: Motility Effects after Inhalation of the Essential Oils and of Some of the Main Constituents in Animal Experiment.

Abstract: Passionsblume und Lindenbluten: Motorik bei Tieren nach Inhalation der atherischen Ole und einiger Hauptbestandteile

Chiral Compounds of Essential Oils, VII: Quality Evaluation of Mentha Oils, Using Enantioselective CGC‐Analysis of Monoterpenoid Constituents

Abstract: Combinations of two or three capillary columns, coated with modified cyclodextrins are used as chiral CGC-separation systems for the direct stereo-differentiation of menthone (1), isomenthone (2), menthol (3), and menthyl-acetate (4), to evaluate their enantiomeric ratios in mentha oils. Optical purity of 1–4 is discussed as an indicator of the natural origin of mint and peppermint oils. Chirale Verbindungen aetherischer Ole, 7. Mitt. : Bewertung von Mentha-Olen durch enantioselektive CGC-Analyse von Monoterpen-Bestandteilen. Kombinationen aus zwei bzw. drei Kapillarsaulen, die mit modifizierten Cyclodextrinphasen belegt sind, werden als chirale Trennsysteme zur direkten Stereodifferenzierung von Menthon (1), Isomenthon (2), Menthol (3) und Menthylacetat (4) beschrieben und deren Enantiomerenverhaltnisse in Mentha-Olen bestimmt. Die optische Reinheit der Monoterpene 1–4 wird als Indikator fur die naturliche Herkunft von Minz- und Pfefferminzolen diskutiert.

Relationship of hypolipidemic and antineoplastic activities of tricyclohexyl- and triphenylphosphine boranes, carboxyboranes, cyanoboranes, and related derivatives.

Abstract: 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, ie 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 Beziehungen zwischen lipidsenkenden Eigenschaften und antineoplastischer Aktivitat von Tricyclohexyl- und Triphenylphosphin-boranen, Carboxyboranen, Cyanoboranen und verwandten Verbindungen Tricyclohexyl- und Triphenylphosphinborane, Carboxyborane und Cyanoborane wurden hergestellt Diese Verbindungen sind bei Nagetieren wirksame Lipidsenker mit antineoplastischen und entzundungshemmenden Eigenschaften, die zugleich gegen die ublichen menschlichen Zellkulturen, die als Standards eingesetzt wurden, cytotoxisch wirken Die Verbindungen mit den besten Lipidsenker-Eigenschaften — Senkung des Serumcholesterols und der Triglyceride um mehr als 40% — waren Diphenyl-(4-methylphenyl)-phosphinboran und Triphenylphosphin-carboxyboran Starkere antineoplastische Wirkung gegen Ehrlich-Ascites Carcinom zeigten ua Triphenylphosphin-cyanoboran, 2-Amino-4-methylpyridin-cyanoboran und 2-Aminopyridin-cyanoboran Die meisten Derivate waren gut wirksam gegen L1210-lymphoide Leukamie der Maus, uterine HeLaS-Zellen und menschliche Gliomazellen Ausgewahlte Verbindungen unterdrucken das Zellwachstum des Colon-Adenocarcinoms, des KB Nasopharynx und des Osleosarcoms Tricyclohexyl- und Triphenylphosphinborane und Carboxyderivate der letztgenannten Verbindungen waren gute Entzundungshemmer

[Synthesis of enantiomerically pure 6,10-epoxybenzocycloocten-7-amines with CNS activity].

Abstract: In an oxa-Pictet-Spengler reaction the methyl (S)-phenyllactate 6 and methyl levulinate (7a) are condensed to the 2-benzopyrans cis-8a and trans-8a, which react with CH3I to yield the dimethyl ethers cis-9a and trans-9a. Cis-9a and trans-9a can be separated by medium pressure liquid chromatography. In the subsequent Dieckmann-Cyclisation cis-9a is transformed to the laevorotatory beta-ketoester (-)-10a, while the dextrorotatory enantiomer (+)-10a is obtained from trans-9a after C-3-epimerisation. With Eu(hfc)3 the ketone (-)-11, prepared by saponification and decarboxylation of (-)-10a, proves to be enantiomerically pure. By reductive amination, ketone (-)-11 is transformed to the amines (-)-12a and (-)-12b. Symptoms typical for central damping are caused after i.p. application of (-)-12a and (-)-12b to mice. In the mouse writhing-test (-)-12a HCl affords an ED50-value of 7.0 mg/kg, comparable with the ED50-value of tramadol.

Synthesis and antiprotozoal properties of 1,2,6-thiadiazine 1,1-dioxide derivatives.

Abstract: The synthesis and spectroscopical data of 1,2,6-thiadiazine 1,1-dioxides, designed as antiprotozoal agents, are reported. The in vitro trichomonacidal and trypanocidal activities of new compounds and their precursors were evaluated against Trichomonas vaginalis and Trypanosoma cruzi. The chemoprophylactic activity on mice treated with blood infected with T. cruzi and their mortality percentage were tested. Compounds 2 and 8b show a higher chemoprophylactic activity and lower mortality percentage than Nifurtimox used as reference drug. Synthese und Wirkung von 1,2,6-Thiadiazin-1,1-dioxiden gegen Protozoen Uber Synthese und spektroskopische Eigenschaften von 1,2,6-Thiadiazin-1,1-dioxiden, entwickelt als Antiprotozoenmittel, wird berichtet. Die trichomonacide und trypanocide Aktivitat dieser neuen Verbindungen wurde in vitro gegen Trichomonas vaginalis und Trypanosoma cruzi gepruft. Die chemoprophylaktische Wirkung an Mausen, behandelt mit T. cruzi infiziertem Blut, sowie die Sterblichkeitsraten wurden festgelegt. Die Verbindungen2 und 8b zeigen hohere chemoprophylaktische Wirkungen und niedrigere Sterblichkeitsraten als der Vergleich Nifurtimox.

Synthesis and preliminary pharmacological study of thiophene analogues of the antipyretic and analgesic agent ethenzamide.

Abstract: 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.

Enantiomerically pure aminoindolizines: bicyclic ergoline analogues with dopamine autoreceptor activity.

Abstract: The development of drugs which stimulate selectively the prejunctional dopamine receptor has become a major challenge in recent years1,2), These autoreceptor agonists decrease synthesis and release of dopamine (OA), Thus, the symptoms of schizophrenia originated from dopamine hyperactivity in the mesolimbic system should be reduced. On the other hand, it has been shown that OA autoreceptor agonists fail to reveal classical OA antagonist side effects like catalepsy, when given to animals3). Since the highly sensitive OA autoreceptor is assumed to resemble the postsynaptic 0-2 receptor4•5), we planned to develop novel autoreceptor agonists by specific structural modifications of known 0-2 agonists. One

Synthesis and Structural Evaluations of Thiazolo[3,2-a]pyrimidine Derivatives

Abstract: 2-Thioxo-1,2,3,4-tetrahydropyrimidine derivatives 1 were reacted with phenacyl bromide in glacial acetic acid to obtain thiazolo[3,2-a]pyrimidine derivatives. UV-, IR-, and 1H-NMR spectra and elementary analysis data confirm structures 3.1H-{1H}-NOE techniques showed that the isolated products are H-5 isomers. Synthese und Strukturaufklarung von Thiazolo[3,2-a]pyrimidin-Derivaten Thiazolo[3,2-a]pyrimidine 3 wurden durch Umsetzung der 2-Thioxo-1,2,3,4-tetrahydropyrimidine 1 mit Phenacylbromid in Eisessig hergestellt. Die Struktur der Substanzen wurde durch Elementar-, UV-, IR-, und 1H-NMR-Analyse gesichert. 1H-[1H]-NOE Methoden zeigen, das die isolierten Produkte H-5-Isomere sind.

Nitroimidazoles, XIV: Synthesis of 4-nitroimidazoles with 1-substituents containing acid, ester or phenol functions, and radiosensitizing efficiency of some of these compounds.

Abstract: 1, 4-Dinitroimidazole and 1, 4-dinitro-2-methylimidazole were reacted with aminocarboxylic acids and their esters, aminosulfonic acids, and aminophenol to obtain the corresponding 1-substituted-4-nitroimidazoles. The radiosensitizing efficiency of some esters of 2-(4-nitro-1-imidazolyl)alkanecarboxylic acids was tested. Nitroimidazole, 14. Mitt.: Synthese von N1-substituierten 4-Nitroimidazolen mit Saure-, Ester- und Phenol-Funktionen und ihre strahlensensibilisierenden Eigenschaften 1, 4-Dinitroimidazole und 1, 4-Dinitro-2-methylimidazole werden mit Aminocarbonsauren und ihren Estern, Aminosulfonsauren und Aminophenolen zu den entspr. N1-substituierten 4-Nitroimidazolen umgesetzt. Die strahlensensibilisierenden Eigenschaften einiger Ester der 2-(4-Nitro-1-imidazolyl)-alkancarbonsauren wurden untersucht.

Benzo[b]thiophenes, Part I: Synthesis and antimicrobial activity of benzo[b]thienyl-1,3,4-oxadiazole, -1,2,4-triazoline, and -thiazoline derivatives.

Abstract: 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. Benzo[b]thiophene, 1. Mitt. : Synthese und antimikrobielle Wirkung von Benzo[b]thienyl-1,3,4-oxadiazol-, -1,2,4-triazol- und -thiazolin-Derivaten Vier neue Serien von Benzo[b]thiophen-Derivaten mit verschiedenen Thiosemicarbazid-, 1,3,4-Oxadiazol-, 1,2,4-Triazolin- und Thiazolin-Resten wurden synthetisiert und auf antimikrobielle Wirksamkeit gepruft.

Amino Acids, XII: (±)Pipecolic Acid Derivatives ‐ Part 2: An Expedient Synthetic Entry to Substituted Pipecolic Acids

Abstract: 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 acis/trans ratio of 1:1. Contrary to this result, reduction of 11 provides 13a/13b in a ratio of ≧ 95/5.

Researches on antibacterial and antifungal agents, XIV: Thiophene analogues of bifonazole.

Abstract: 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

Nitroketenaminale, 7. Mitt.: Synthese von substituierten 2-Amino-3-nitropyridinen aus 1,3-Biselektrophilen und 2-Nitroethen-1,1-diamin

Abstract: Die Umsetzung der Enone 1a-f mit dem Nitroketenaminal 2 fuhrt zu den 4,6-substituierten 2-Amino-1,4-dihydropyridinen 3a-f, von denen in unbefriedigenden Ausbeuten 3a-c,f durch Luft zu den Pyridinen 4a-c,f oxidiert werden, 5- bzw. 6-substituierte 2-Amino-3-nitropyridine (9a,b bzw. 11) sind aus 8a,b bzw. 10 und 2 zuganglich. Nitroketenaminals, VII: Synthesis of Substituted 2-Amino-3-nitropyridines from 1,3-Biselectrophiles and 2-Nitroethen-1,1-diamine The reaction of the enones 1a-f with the nitroketenaminal 2 leads to the 4,6-disubstituted 2-amino-1,4-dihydro-3-nitropyridines 3a-f. Compounds 3a-c,f are oxidized in low yields by air to the pyridines 4a-c,f. 5- and 6- substituted 2-amino-3-nitropyridines (9a,b and 11) can be prepared from 2, 8a,b, and 10, respectively.

Preparation and diuretic properties of novel amiloride analogues

Abstract: 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. Darstellung und diuretische Eigenschaften neuer Amiloridanaloga Es wurden funfzehn neue Amiloridanaloga dargestellt und ihre diuretischen Eigenschaften an White Whistar-Ratten mit denen von Amilorid und Triamteren verglichen. Wahrend keines der 6-substituierten Derivate signifikante natriuretische und antikaliuretische Wirkung zeigte, erwiesen sich funf der in Position 2 modifizierten Verbindungen als gleich gut oder besser wirksam als die Referenzsubstanzen. Die Ergebnisse werden im Hinblick auf die chemische Struktur und physikochemischen Eigenschaften diskutiert.

Synthesis and antimicrobial activity of 3-(substituted-phenyl)-sydnones.

Abstract: 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. Synthese und antimikrobielle Aktivitat von 3-(substituierten-Phenyl) sydnon-Derivaten 3-(3- oder 4-Acetylphenyl)sydnone 7,8 wurden aus den Glycin-Derivaten 3, 4 durch Nitrosieren zu 5, 6 und Cyclisieren mittels Essigsaureanhydrid aufgebaut. Die Sydnon-Derivate 15, 16, die Chalkon-Teile tragen, wurden analog aus den Chalkonen 11, 12 hergestellt. Die Sydnon-Derivate wurden auf antimikrobielle Aktivitat gepruft.

Trifluormethyl‐substituierte, heterocyclisch anellierte Pyridine durch intramolekulare Diels‐Alder‐Cycloaddition mit inversem Elektronenbedarf

Abstract: Wir beschreiben eine Synthese von 3-Methylthio-6-trifluormethyl-1, 2, 4-triazin (5) aus Trifluordibromaceton (1) und S-Methylthiosemicarbazid. Nucleophile Substitution der Thiomethylgruppe von 5 durch die Alkoxide von 6a-c bzw. durch das ω-Amino-1-alkin 11 fuhrt zu den Triazinen 7 bzw. 12, die uber eine Sauerstoff-bzw. eine NH-Brucke mit dem Seitenkettendienophil verknupft sind. Triazine mit Schwefel als Bindeglied zwischen Dien und Dienophil wie 20a-c werden aus 1 und dem Isothiosemicarbazid-Salz 17 hergestellt. Die Triazine 7, 12 und 20 reagieren beim Erhitzen in Chlorbenzen bzw. Diphenylether zu den neuen heterocyclisch anellierten Pyridinen 8–10, 13 und 23-25. Trifluoromethyl Substituted Heterocyclically Annulated Pyridines by Intramolecular Diels-Alder-Cycloaddition with Inverse Electron Demand A synthesis of 3-methylthio-6-trifluoromethyl-1, 2, 4-triazine (5) is described using dibromotrifluoroaceton (1) and S-methylthiosemicarbazide as starting materials. Nucleophilic displacement of the thiomethylgroup in 5 by the alkoxides of 6a-c or by the ω-amino-1-alkynes 11 leads to the triazines 7 and 12, respectively, with oxygen- or nitrogen-linked side chains. Triazines as 20a-c with sulfur as a link between diene and dienophile are formed by the reaction of S-ω-alkynylisothiosemicarbazide salts 17 with 1. On heating in chlorobenzene or diphenylether the triazines 7, 12, and 20 yield the novel heterocyclicly annulated pyridines 8-10, 13, and 23-25.

Studies on annelated [1,4]benzothiazines and [1,5]benzothiazepines, V. Synthesis and biological activity of N-2 alkylamino derivatives of 4,5-dihydro-s-triazolo[3,4-d]-1,5-benzothiazepine.

Abstract: 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. Synthese und biologische Aktivitat von N-2 Alkylaminoderivaten des 4,5-Dihydro-s-triazolo[3,4-d]-1,5-benzothiazepins Die Synthese einer neuen Reihe von N-2 Alkylaminoderivaten des 4,5-Dihydro-s-triazolo[3,4-d]-1,5-benzothiazepins wurde mit 2,3-Dihydro-1,5-benzothiazepin-4(5H)onen und seinen 2-Methyl- und 2-Phenylderivaten als Ausgangsprodukten durchgefuhrt. - Die Verbindungen wurden in vitro auf ihre antimikrobielle Wirkung gepruft, aber sie zeigten keine signifikanten antibakteriellen (Gram-positive Erreger) oder antimycotischen Effekte. - Die Verbindungen 7a-j, 8a-j, 9a-j, 10a-j und 11a-j wurden auf ihre ZNS-Wirkung an der Maus untersucht, und einige von ihnen zeigten interessante Wirkungen.

Assessment of anti-HIV activity of some benzimidazolylthiazoles.

Abstract: 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.

Dimerisierende Kondensation von Alkylidenpropandinitrilen und Alkylidencyanamiden. - Ein allgemeines Syntheseprinzip für Anilin-, Aminopyridin- und Aminopyrimidin-Derivate

Abstract: Die basenkatalysierte dimerisierende Kondensation von (α-Methylthioalkyliden)propandinitrilen (z.B. 8) liefert 2-Aminobenzol-1,3-dicarbonitrile (z.B. 13), von (α-Methylthioalkyliden)cyanamid (z.B. 14) 2-Aminopyrimidine (z.B. 16, 37). Die gemischte Kondensation von (α-Aminoalkyliden)propan-dinitrilen (z.B. 20) mit (α-Methylthioalkyliden)cyanamiden fuhrt zu Pyrimidin-5-carbonitrilen (z. B. 23, 28, 40). Dimerizing Condensation of Alkylidenepropanedinitriles and Alkylidenecyanamides. - A General Approach to Aniline, Aminopyridine, and Aminopyrimidine Derivatives The base catalyzed dimerizing condensation of (α-methylthioalkylidene)propanedinitriles (e.g.8) yields 2-aminobenzene-1,3-dicarbonitriles (e.g.13), of (α-methylthioalkylidene)cyanamides (e.g.14) 2-animopyrimidines (e.g.16, 37). The mixed condensation of (α-aminoalkylidene)propanedinitriles (e.g.20) with (α-methylthioalkylidene)cyanamides leads to the formation of pyrimidine-5-carbonitriles (e.g. 23, 28, 40).

Bindung von 5-Fluorouracil an Serumproteinfraktionen, Erythrozyten und Ghosts unter in vitro Bedingungen

Abstract: The binding of 5-fluorouracil (1) to erythrocytes and to serum proteins under in vitro conditions was investigated. The binding rate of 1 to erythrocytes is dose-independent and amounts from 16.8 to 31.7% (concentration range 1 to 20 micrograms/ml). The mean coefficient of partition for erythrocytes is 0.25 (+/- 0.03), no binding to ghosts was observed. 1 is bound at about 4% to proteins, whereby 0.7% are bound to alpha-globulin, 0.8% to beta-globulin, 1.6% to gamma-globulin, and 0.8% to albumine. The mean partition coefficient for proteins is 0.04 (+/- 0.006).

First Reactions of 2,2′-Bisindolyls with Electrophilic Azo Compounds and Diethyl Mesoxalate

Abstract: Conformations and some electronic properties of the 2,2′-bisindolyls 6 were calculated for the prediction of probable Diels-Alder reactivity, in analogy to previous work on 2-vinylindoles. First reactions with dienophiles revealed that compounds 6 did not participate in [4 + 2]cycloadditions but rather underwent simple electrophilic substitutions at the enamine function with, above all, some heterodienophiles. Erste Reaktionen von 2,2′-Bisindolylen mit elektrophilen Azoverbindungen und Diethylmesoxalat Zur Vorhersage moglicher Diels-Alder-Reaktionen an 2,2′-Bisindolylen 6 werden Berechnungen zur Konformation und uber elektronische Eigenschaften durchgefuhrt. Die erstmals durchgefuhrten Reaktionen dieser mit 2-Vinylindolen verwandten Systeme 6 mit Dienophilen zeigen allerdings, das keine [4 + 2]Cycloadditionen eintreten. An der Enamin-Struktur von 6 erfolgen in erster Linie einfache elektrophile Substitutionen.

Facile Synthesis of Fused Heterocycles through 2-Bromobenzofurylglyoxal-2-arylhydrazones

Abstract: 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. Synthese kondensierter Heterocyclen aus 2-Brombenzofurylglyoxal-2-arylhydrazonen Einige neue Imidazo[1,2-a]pyridin-, Pyrazolo[5,1-a]imidazol-, Quinazolinon-, 1,4-Benzothiazine- und Pyrazol-Derivate wurden synthetisiert durch die Reaktionen von 2-Brombenzofurylglyoxal-2-arylhydrazonen mit verschiedenen Reagenzien. Die Strukturen der neu synthetisierten Derivate wurden mittels Elementaranalyse und spektroskopischer Daten geklart.