TY - JOUR A1 - Tacke, R. A1 - Strecker, M. A1 - Sheldrick, W. S. A1 - Heeg, E. A1 - Berndt, B. A1 - Knapstein, K. M. T1 - Sila-Pharmaka, 14. Mitt. Darstellung und Eigenschaften sowie Kristall-und Molekülstruktur von Sila-Difenidol JF - Zeitschrift für Naturforschung B N2 - Sila-difenidol (6b), a sila-analogue of the drug difenidol (6a), was synthesized according to Scheme 1. 6b and its new precursors 3 and 5 were characterized by their physical and chemical properties, and their structures confirmed by elementary analyses, 1H NMR and mass spectroscopy. 6 b crystallizes orthorhombic \(P2_12_12_1\) with a = 11.523(1), b = 14.366(4), c = 11.450(1) Å, Z = 4, \(D_{ber} = 1.14 gcm^{-3}\). The structure was refined to R = 0.050 for 1897 reflexions. A strong nearly linear intramolecular O-H···N hydrogen bond of 2.685 Å is observed. The anticholinergic, histaminolytic and musculotropic spasmolytic activities of 6 a and 6 b are reported. KW - sila-difenidol KW - syntheses KW - crystal structure KW - molecular structure KW - biological activity Y1 - 1979 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128391 VL - 34 IS - 9 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Strecker, M. A1 - Sheldrick, W. S. A1 - Ernst, L. A1 - Heeg, E. A1 - Berndt, B. A1 - Knapstein, C.-M. A1 - Niedner, R. T1 - Sila-Pridinol und Pridinol: Darstellung und Eigenschaften sowie Strukturen im kristallinen und gelösten Zustand T1 - Sila-Pridinol and Pridinol: Preparation and Properties as weil as Structures ln the Solid Stateand in Solution N2 - Sila-Pridinol (2 b), ein Sila-Analogon des Anticholinergicums Pridinol (2a), wurde auf zwei verschiedenen Wegen dargestellt. Die Kristall- und Molekülstrukturen von 2 a und 2 b wurden röntgenstrukturanalytisch bestimmt. 2a bildet im festen Zustand intramolekulare Wasserstoffbrückenbindungen aus, während sich in kristallinem 2 b zentrosymmetrische, durch intermolekulare H-Brückenbindungen verknüpfte cyclische Dimere finden. IR- und \8^1\)H-NMR-spektroskopische sowie kryoskopische Untersuchungen ergaben Informationen über die Strukturen von 2a und 2 b in verschiedenen Lösungsmitteln. - Die pharmakologischen und toxikologischen Eigen" schaften von 2a und 2b wurden unter dem Gesichtspunkt bekannter Struktur-Wirkungs-Beziehungen vergleichend untersucht. 2 b erwies sich als ein etwa fünfmal so starkes Anticholincrgicum wie 2a. N2 - Sila"pridinol (2 b), a sila"analogue of the anticholinergic pridinol (2a). was prepared by two different routes. The crystal and molecular structures of 2 a and 2 b were determined by X-ray structural analyses. 2a forms intramolecular hydrogen bonds in the solid state, whereas centrosymrnetric cyclic dimers linked through intermolecular hydrogen bonds are observed for crystalline 2 b. IR- and \(^1\)H NMR spectroscopic as weil as cryoscopic studies yielded information ab out the structures of 2a and 2 bin different solvents. - The pharmacological and toxicological properties of2a and 2b were compared with one another on the basis ofknown structure-activity relationships. The anticholinergic properties of 2b were found tobe about five times as strong as those of 2a. KW - Anorganische Chemie Y1 - 1980 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63654 ER - TY - JOUR A1 - Beck, Katherina A1 - Ehmann, Nadine A1 - Andlauer, Till F. M. A1 - Ljaschenko, Dmitrij A1 - Strecker, Katrin A1 - Fischer, Matthias A1 - Kittel, Robert J. A1 - Raabe, Thomas T1 - Loss of the Coffin-Lowry syndrome-associated gene RSK2 alters ERK activity, synaptic function and axonal transport in Drosophila motoneurons JF - Disease Models & Mechanisms N2 - Plastic changes in synaptic properties are considered as fundamental for adaptive behaviors. Extracellular-signal-regulated kinase (ERK)-mediated signaling has been implicated in regulation of synaptic plasticity. Ribosomal S6 kinase 2 (RSK2) acts as a regulator and downstream effector of ERK. In the brain, RSK2 is predominantly expressed in regions required for learning and memory. Loss-of-function mutations in human RSK2 cause Coffin-Lowry syndrome, which is characterized by severe mental retardation and low IQ scores in affected males. Knockout of RSK2 in mice or the RSK ortholog in Drosophila results in a variety of learning and memory defects. However, overall brain structure in these animals is not affected, leaving open the question of the pathophysiological consequences. Using the fly neuromuscular system as a model for excitatory glutamatergic synapses, we show that removal of RSK function causes distinct defects in motoneurons and at the neuromuscular junction. Based on histochemical and electrophysiological analyses, we conclude that RSK is required for normal synaptic morphology and function. Furthermore, loss of RSK function interferes with ERK signaling at different levels. Elevated ERK activity was evident in the somata of motoneurons, whereas decreased ERK activity was observed in axons and the presynapse. In addition, we uncovered a novel function of RSK in anterograde axonal transport. Our results emphasize the importance of fine-tuning ERK activity in neuronal processes underlying higher brain functions. In this context, RSK acts as a modulator of ERK signaling. KW - mrsk2 KO mouse KW - S6KII RSK KW - transmission KW - neuromuscular junction KW - synapse KW - MAPK signaling KW - axonal transport KW - motoneuron KW - RSK KW - Drosophila KW - mechanisms KW - plasticity KW - protein kinase KW - signal transduction pathway KW - mitochondrial transport KW - glutamate receptor Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145185 VL - 8 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Zimonyi-Hegedüs, E. A1 - Strecker, M. A1 - Heeg, E. A1 - Berndt, B. A1 - Langner, R. T1 - Sila-Analogon des Tiemoniumiodids T1 - Sila-Analogue of Tiemonium Iodide N2 - Sila-Tiemoniumiodid (16b), ein Sila-Analogon des Anticholinergicums Tiemoniumiodid (16a), und das Sila-Analogon 14b der entsprechenden Tiemonium-Base 14a wurden erstmalig synthetisiert.14b und 16b sowie die Vorstufen 10-13 und 15 wurden in ihren physikalischen und chemischen Eigenschaften charakterisiert und in ihrer Struktur durch Elementaranalysen sowie \(^1\)H-NMR- und Massenspektren sichergestellt. Die spasmolytischen Eigenschaften der Paare 14a/14b und 16a/16b wurden am isolierten Meerschweinchendarm vergleichend untersucht. N2 - Silatiemonium iodide (16b), a sila-analogue of the anticholinergic tiemonium iodide (16a), and the siJa-analogue 14b of the corresponding free base 14a were synthesized for the first time. Compounds 14b and 16b as weil as their precursors 10-13 and 15 were characterized by their physical and chemical properties. Their structures were confirmed by elementary analyses, (^1\)H NMRand massspectroscopy. The spasmolytic properties of the pairs 14a/14b and 16a/16b were compared on the isolated guinea pig ileum. KW - Anorganische Chemie Y1 - 1980 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63669 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Strecker, M. A1 - Lambrecht, G. A1 - Moser, U. A1 - Mutschler, E. T1 - (2-Aminoethyl)-cycloalkylphenylsilanole: Bioisosterer C/Si-Austausch bei Parasympatholytika vom Typ des Trihexyphenidyls, Cycrimins und Procyclidins T1 - (2-Aminoethyl)cycloalkylphenylsilanols: Bioisosteric C/Si Exchange in Parasympatholy1ics of lhe Trihexyphenidyl, Cycrimine, and Procyclidine Type N2 - Die Synthese der (2-Aminoethyl)cycloalkylphenylsilanole Sb (Sila-Trihexyphenidyl), 6b (SilaCycrimin), 7 b (Sila-Procyclidin) und Sb wird beschrieben. Sb- Sb wurden - ausgehend von Cl\(_2\)(C\(_6\)H\(_5\))SiCH = CH\(_2\) (9) - durch eine fünfstufige Reaktionsfolge mit einer Gesamtausbeute von 32- 40% erhalten. Am isolierten Ileum des Meerschweinchens wurden die C/Si-Paare Sa, b- 8a, b vergleichend auf ihre antimuskarinische Aktivität geprüft. Die durch die Sila-Substilution von Sa-8a erreichte Zunahme der Affinität zum Muskarinrezeptor ist deutlich weniger ausgeprägt als bei den strukturverwandten C/Si-Paaren I a, b- 4a, b. N2 - Thc synthesis of thc (2-aminoethyl)cycloalkylphenylsilanols Sb (sila-trihexyphenidyl), 6b (silacycrimine), 7b (sila-procyclidine), and Sb is described. Starting with Cl2(C6H5)SiCH = CH2 (9), Sb- 8 b were obtained by five reaction steps with a total yield of 32- 40%. The C/Si pairs Sa,b- 8a, b were tested for antimuscarinic activity on the isolated guinea-pig ileum. Thc increase of affinity for the muscarinic reccptor caused by sila-substitution of S a- 8a is less marked than in the case of the structurally related C/Si pairs la,b-4a,b. KW - Anorganische Chemie Y1 - 1983 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63741 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Strecker, M. A1 - Lambrecht, G. A1 - Moser, U. A1 - Mutschler, E. T1 - Bioisosterer C/Si-Austausch bei Parasympatholytika vom Typ des Pridinols T1 - Bioisosterie C/Si Exchange in Parasympatholytia of tbe Pridinol Type N2 - Die Synthese der (2·Aminoethyl)diphenylsilanole 3b und 4b wird beschrieben. Die parasympatholytischen Eigenschaften der CISi-Paare la/lb-4a/4b wurden am isolierten Ileum des Meerschweinchens untersucht. In allen Fällen führt der C/Si-Austausch zu einer Zunahme der Affinität zum Muskarin-Rezeptor. N2 - The synthesis of the (2·aminoethyl)diphenylsilanols 3b and 4b is described. The Q'Si pairs lallb-4a/4b were tested for atropine-like activity on the isolated guinea-pig ileum. In all cases the C/Si exchange Ieads to an increased affinity for the muscarine-sensitive acetylcholine receptor. KW - Anorganische Chemie Y1 - 1984 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63766 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Strecker, M. A1 - Niedner, R. T1 - Cholinesterase-hemmende Organophosphorsäureester und ihre Sila-Analoga T1 - Organophosphates with Anticholinesterase Activity and their Sila-Analogues N2 - Die Organophosphorsäureester la-4a und ihre Sila-Analoga lb-4b des Typs R\(^1\)R\(^2\)P(O)( p-OC\(_6\)H\(_4\)ElMe\(_3\)) (EI = C, Si) wurden synthetisiert. Die Kohlenstoff-Verbindungen 1 a- 4a zeigen hinsichtlich ihrer Anticholinesterase-Aktivität die gleichen Struktur-Wirkungs-Beziehungen wie die Silicium-Verbindungen 1 b- 4 b. Letztere sind jeweils wirksamer als die entsprechenden C-Analoga. N2 - The organophosphates la-4a and their sila-analogues lb-4b of the type R\(^1\)R\(^2\)P(O)( p-OC\(_6\)H\(_4\)ElMe\(_3\) (El = C, Si) were synthesized. With regard to their anticholinesterase activity, the carbon compounds ta- 4a exhibit the same structure-activity relationships as the silicon compounds 1 b- 4b. The latter are more activ than the corresponding C-analogues. KW - Anorganische Chemie Y1 - 1981 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63689 ER -