TY - JOUR A1 - Rettenmayr, N. M. A1 - Rodrigues de Miranda, J. F. A1 - Rijntjes, N. V. M. A1 - Russel, F. G. M. A1 - van Ginneken, C. A. M. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Lambrecht, G. A1 - Mutschler, E. T1 - Pharmacokinetic properties of the antimuscarinic drug [\(^3\)H]-hexahydro-sila-difenidol in the rat N2 - The pharmacokinetics of tritiated hexahydrosila- difenidol ([\(^3\)H]-HHSiD) were examined in rats. Furthermore, the distribution of radioactivity was studied by means of whole body autoradiography. After i. v. administration of 2.9 mg/kg HHSiD plus [\(^3\)H]-HHSiD to anaesthetized rats bearing a catheter implanted in the ductus choledochus and receiving a mannitol infusion, HHSiD was rapidly distributed and metabolized. Only 5% ofthe radioactivity was recovered in blood after 23 s and 0.4% after 2.5 h. 64% of the plasma radioactivity could be extracted with hexane from the samples taken 23 s after administration. 52% of the radioactivity was eliminated within 2.5 h, 13% by urinary and 39% by biliary excretion. Following oral administration of 8.6 mg/kg HHSiD plus [\(^3\)H]-HHSiD there was an absorption of approximately one fourth of the administered radioactivity within 4 h. By means of whole body autoradiography (i. v. injection) as well as by tissue distribution measurement the highest Ievels of radioactivity were found in bile, urine, lung, kidney, adrenals, liver and .pancreas. Thus, after i. v. administration to rats HHSiD is rather quickly distributed, metabolized and excreted. This explains its low antimuscarinic potency in vivo. KW - Anorganische Chemie KW - Pharmacokinetics KW - [3H]-Hexahydro-siladifenidol KW - Sila-drug KW - Rat KW - Autoradiography Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64022 ER - TY - JOUR A1 - Waelbroeck, M. A1 - Camus, J. A1 - Tastenoy, M. A1 - Lambrecht, G. A1 - Mutschler, E. A1 - Kropfgans, M. A1 - Sperlich, J. A1 - Wiesenberger, F. A1 - Tacke, R. A1 - Christophe, J. T1 - Thermodynamics of antagonist binding to rat muscarinic \(M_2\) receptors: antimuscarinics of the pridinol, sila-pridinol, diphenidol and sila-diphenidol type JF - British Journal of Pharmacology N2 - 1 We studied the effect of temperature on the binding to rat heart \(M_2\) muscarinic receptors of antagonists related to the carbon/silicon pairs pridinol/sila-pridinol and diphenidol/sila-diphenidol (including three germanium compounds) and six structurally related pairs of enantiomers [(R)- and (S)-procyclidine, (R)- and (S)-trihexyphenidyl, (R)- and (S)-tricyclamol, (R)- and (S)-trihexyphenidyl methiodide, (R)- and (S)-hexahydro-diphenidol and (R)- and (S)-hexbutinol]. Binding affinities were determined in competition experiments using \([^3H]\)-N-methyl-scopolamine chloride as radioligand. The reference drugs were scopolamine and N-methyl-scopolamine bromide. 2 The affinity of the antagonists either increased or decreased with temperature, van 't Hoff plots were linear in the 278–310°K temperature range. Binding of all antagonists was entropy driven. Enthalpy changes varied from large negative values (down to \(−29 kJ mol^{−1}\)) to large positive values (up to \(+ 30 kJ mol^{−1}\)). 3 (R)-configurated drugs had a 10 to 100 fold greater affinity for \(M_2\) receptors than the corresponding (S)-enantiomers. Enthalpy and entropy changes of the respective enantiomers were different but no consistent pattern was observed. 4 When silanols \((R_3SiOH)\) were compared to carbinols \((R_3COH)\), the affinity increase caused by C/Si exchange varied between 3 and 10 fold for achiral drugs but was negligible in the case of chiral drugs. Silanols induced more favourable enthalpy and less favourable entropy changes than the corresponding carbinols when binding. Organogermanium compounds \((R_4Ge)\) when compared to their silicon counterparts (R4Si) showed no significant difference in affinity as well as in enthalpy and entropy changes. 5 Exchange of a cyclohexyl by a phenyl moiety was associated with an increase or a decrease in drug affinity (depending on the absolute configuration in the case of chiral drugs) and generally also with a more favourable enthalpy change and a less favourable entropy change of drug binding. 6 Replacement of a pyrrolidino by a piperidino group and increasing the length of the alkylene chain bridging the amino group and the central carbon or silicon atom were associated with either an increase or a decrease of entropy and enthalpy changes of drug binding. However, there was no clear correlation between these structural variations and the thermodynamic effects. 7 Taken together, these results suggest that hydrogen bond-forming OH groups and, to a lesser extent, polarizable phenyl groups contribute significantly to the thermodynamics of interactions between these classes of muscarinic antagonists and \(M_2\) muscarinic receptors. KW - entropy KW - binding KW - M2 muscarinic receptors KW - thermodynamics KW - van 't Hoff plot KW - enthalpy Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128439 VL - 109 IS - 2 ER - TY - JOUR A1 - Waelbroeck, M. A1 - Camus, J. A1 - Tastenoy, M. A1 - Mutschler, E. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Schjelderup, L. A1 - Aasen, A. A1 - Lambrecht, G. A1 - Christophe, J. T1 - Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors N2 - Wc invcstigatcd thc binding properlies of thc (R)- and (Sl-cnantiomcrs of thc muscarinic antagonists trihcxyphcnidyl, procyclidinc, hcxahydro-difcnidol. p-fluoro-hcxahydro-difcnidol. hcxbutinol, p-fluoro-hcxbutinnl. and thcir corrcsponding methiodidcs at muscarinic M\(_1\), M\(_2\)• M\(_3\) and M\(_4\) receptor subtypes. In addition. binding properlies of thc (R)- and (S)-cnantiomcrs of oxyphcncycliminc wcrc studicd. The {R)- cnantiomcrs (cutomcrs} of all the compounds had a grcatcr affinity than the (S)-isomcrs for thc four muscarinic rcccptor subtypcs. Thc binding pattcrns of thc (R)- and (S)-enantiomers wcrc gcncrally different. We did not obscrvc any gcncral corrclation hctwccn thc potcncy of thc high-affinity enantiomer and Lhc affinity ratio (cudismic ratio) of the two cnantiomcrs. Thc rcsuhs arc discusscd in tcrms of a 'four suhsitcs' binding modcl. KW - Anorganische Chemie KW - Muscarinic receptors KW - Hexahydro-difenidol KW - Oxyphencyclimine Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64237 ER - TY - JOUR A1 - Waelbroeck, M. A1 - Tastenoy, M. A1 - Camus, J. A1 - Christophe, J. A1 - Strohmann, C. A1 - Linoh, H. A1 - Zilch, H. A1 - Tacke, Reinhold A1 - Mutschler, E. A1 - Lambrecht, G. T1 - Binding and functional properties of antimuscarinics of the hexocyclium/sila-hexocyclium and hexahydro-diphenidol/hexahydro-sila-diphenidol type to muscarinic receptor subtypes N2 - l In an attempt to assess the structural requirements for the musearlnie receptor selectivity of hexahydro-diphenidol (hexahydro-difenidol) and hexahydro-sila-diphenidol (hexahydro-sila-difenidol), a serles of structurally related C/Si pairs were investigated, along with atropine, pirenzepine and methoctramine, for their binding affinities in NB-OK 1 cells as well as in rat heart and pancreas. 2 The action of these antagonists at musearlnie receptors mediating negative inotropic responses in guinea-pig atrla and ileal contractions has also been assessed. 3 Antagonist binding data indicated that NB-OK 1 cells (M\(_1\) type) as weil as rat heart (cardiac type) and pancreas (glandularjsmooth muscle type) possess different muscarinic receptor subtypes. 4 A highly significant correlation was found between the binding affinities of the antagonists to muscarinic receptors in rat heart and pancreas, respectively, and the affinities to muscarinic receptors in guinea-pig atria and ileum. This implies that the musearlnie binding sites in rat heart and the receptors in guinea-pig atrla are essentially similar, but different from those in pancreas and ileum. 5 The antimuscarinic potency of hexahydro-diphenidol and hexahydro-sila-diphenidol at the three subtypes was inftuenced differently by structural modifications (e.g. quaternization). Different selectivity profiles for the antagonists were obtained, which makes these compounds useful tools to investigate further muscarinic receptor heterogeneity. lndeed, the tertiary analogues hexahydrodiphenidol (HHD) and hexahydro-sila-diphenidol (HHSiD) bad an M\(_1\) = glandularjsmooth muscle > cardiac selectivity profile, whereas the quaternary analogues HHD methiodide and HHSiD methiodide were M\(_1\) preferring (M\(_1\) > glandularjsmooth muscle, cardiac). KW - Anorganische Chemie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63944 ER - TY - JOUR A1 - Waelbroeck, M. A1 - Camus, J. A1 - Tastenoy, M. A1 - Lambrecht, G. A1 - Mutschler, E. A1 - Tacke, Reinhold A1 - Christophe, J. T1 - Stereoselectivity of procyclidine binding to muscarinic receptor subtypes M\(_1\), M\(_2\) and M\(_4\) N2 - The goals of the present study were: (1) to investigate thc binding properlies oi (R)- and (S)-procyclidine and two aehiral derivatives of muscarinic M\(_1\)• M\(_2\) and M\(_4\) receptor subtypes and (2) to identify the interaetions which allow these receptors to diseriminate between the two stereoisomers. (R)-Procyclidine showed a higher affinity for human neuroblastoma NB-OK 1 muscarinie M\(_1\) and rat striatum musearinie M\(_4\) receptors. a~ compared to rat cardiac M\(_2\) receptors. (S)-Procyclidine had a 130-iold lower affinity than (R)-procyclidine for M\(_1\) and M\(_4\) receptors. and a 40-fold lower affinity for M\(_2\) receptors. Pyrrinol. the aehiral diphenyl derivative with the eyclohexyl g.roup of (S}-procyclidine replaeed by a phenyl group, has an eight-fold lower affinity for M\(_1\) and M\(_4\) receptors. as eompared to (R)-procyclidine, and a three-fold lower affinity for M\(_2\) receptors. Hexahydro-procyclidine. the eorresponding achiral dicyclohexyl compound, had a 10- to 20-fold lower affinity than (R)-procyclidine for the three reeeptors. The inerease in binding free energy, which is observed when the phenyl and eyclohexyl groups of procyelidine are separately replaeed by cyclohexyJ and phenyl groups, respectively. was additive in the ease of M\(_1\)• M\(_2\) and M\(_4\) receptcrs. This indicates that the musearinic reeeptor s!ereoseleetivity was based on the eoexistence of two binding sites, one preferring a phenylrather than eyclohexyl group and the seeond preferring a cyclohexyl rather than a phenyl group. In addition. there were aiso binding sites for the hydroxy moiety and the protonated amino group of the ligands. The greater affinity and stereoselectivity of M\(_1\) and M\(_4\) muscarinic receptors for (R)-procyelidine reflected the better fit of the eyclohexyl group of (R)-procyclidine to the subsite of M\(_1\) and M\(_4\) as compared to M\(_2\) receptors. KW - Anorganische Chemie KW - Musearlnie M1 KW - receptors KW - Muscarinie M2 receptors KW - Musearinic M4 receptors KW - Pyrrinol KW - Hexahydro-procyclidine KW - Muscarinic receptors Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64034 ER - TY - JOUR A1 - Lambrecht, G. A1 - Feifel, R. A1 - Wagner-Röder, M. A1 - Strohmann, C. A1 - Zilch, H. A1 - Tacke, Reinhold A1 - Waelbroeck, M. A1 - Christophe, J. A1 - Boddeke, H. A1 - Mutschler, E. T1 - Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes N2 - In an attempt to assess the structural requirements of hexahydro-sila-difenidol for potency and selectivity, a series of analogues modified in the amino group and the phenyl ring were investigated for their affinity to muscarinic M1- (rabbit vas deferens), Mr (guinea-pig atria) and Mr (guinea-pig ileum) receptors. All compounds were competitive antagonists in the three tissues. Their affinities to the three muscarinic receptor subtypes differed by more than two orders of magnitude and the observed receptor selectivities were not associated with high affinity. The pyrrolidino and hexamethyleneimino analogues, compounds substituted in the phenylring with a methoxy group or a chlorine atom as weil as p-fluoro-hexahydro-difenidol displayed the same affinity profile as the parent compound, hexahydro-sila-difenidol: M1 = M3 > M2 • A different selectivity patternwas observed for p-fluoro-hexahydro-sila-difenidol: M3 > M1 > M2 • This compound exhibited its highest affinity for M3-receptors in guinea-pig ileum (pA 2 = 7.84), intermediate affinity for M1-receptors in rabbit vas deferens (pA 2 = 6.68) and lowest affinity for the Mrreceptors in guinea-pig atria (pA 2 = 6.01). This receptor selectivity profile of p-fluoro-hexahydro-sila-difenidol was confirmed in ganglia (M1), atria (M2 ) and ileum (M 3 ) of the rat. Furthermore, dose ratios obtained with either pirenzepine (Mt) or hexahydrosila- difenidol (M2 and M3) and the p-fluoro analogue used in combination suggested that the antagonism was additive, implying mutual competition with a single population of muscarinic receptor subtypes. These results indicate that p-fluoro-hexahydro-sila-difenidol represents a valuable tool for characterization of muscarinic receptor subtypes. KW - Anorganische Chemie KW - Muscarinic receptor subtypes KW - Muscarinic M3selective antagonists KW - Hexahydro-sila-difenidol analogues Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63979 ER - TY - JOUR A1 - Feifel, R. A1 - Wagner-Röder, M. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Waelbroeck, M. A1 - Christophe, J. A1 - Mutschler, E. A1 - Lambrecht, G. T1 - Stereoselective inhibition of muscarinic receptor subtypes by the enantiomers of hexahydro-difenidol and acetylenic analogues N2 - 1 Tbc affinities of the (R)- and (S)-enantiomers of hexahydro-difenidol (1) and its acetylenie analogues hexbutinol (2), hexbutinol methiodide (3) and p-fluoro-hexbutinol (4) (stereochemieal purity > 99.8%) for musearlnie receptors in rabbit vas deferens (M1), guinea-pig atria (M2) and guinea-pig ileum (M3) were measured by dose-ratio experiments. 2 The (R)-enantiomers consistently showed higher aßinities than the (S)-isomers. The stereosclectivity ratios [(R)/(S)] wcrc greatest with thc enantiomers of 1 (vas deferens: 550; ilcum: 191; atria: 17) and least with thosc ofthc p-Fluoro-analogue 4 (vas defercns: 34; ileum: 8.5; atria: 1.7). 3 The enantiomerie potency ratios for compounds 1-4 were highest in rabbit vas deferens, intermediate in guinea-pig ileum and much less in guinea-pig atria. Thus, these ratios may serve as a predietor of muscarinic receptor subtype identity. 4 (S)-p-Fluoro-hexbutinol [(S)-4] showed a novel receptor selectivity profile with preference for M\(_3\) receptors: M\(_3\) > M\(_2\) \(\geq\) M\(_1\)• 5 These results do not conform to Pfeiffer's rule that aetivity differences between enantiomers are greater with more potent compounds. KW - Anorganische Chemie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64002 ER - TY - JOUR A1 - Waelbroeck, M. A1 - Camus, J. A1 - Tastenoy, M. A1 - Mutschler, E. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Lambrecht, G. A1 - Christophe, J. T1 - Binding affinities of hexahydro-difenidol and hexahydro-sila-difenidol analogues at four muscarinic receptor subtypes: constitutional and stereochemical aspects N2 - Hexahydro-sila-difenidoJ and eight analogues behaved as simple cumpetitive inhibitors of eHJN·methyl·scopoJamine binding to homogenates frorn human neuroblastoma NB-OK 1 cells (M\(_1\) sites), rat heart (M\(_2\) sites), rat pancreas (M\(_3\) sites), and rat striatum 'B' sites (M\(_4\) sites). Pyrrolidino- and hexamethyleneimino analogues showed the same sekctivity profile as the parent compound. Hexahydro-sila-difenidol methiodide and the methiodide of p-fluoro-hexahydro·sila-difenidol had a fügher affinity but a lower selectivity than the tertiary amines. Compounds containing a p·methoxy, p-chJoro or p-fluoro substituent in the phenyl ring of hexahydro-sila-difenidol showed a qualitative)y similar selectivity profile as the parent compound (i.e., M\(_1\)= M\(_3\) = M\(_4\) >M\(_2\) ), but up to 16-fold lower affinities. o-Methoxy-hexahydro-sila-difenidol has a lower affinity than hexahydro-sila-difeni.:!o! at the four binding sites. lts selectivity profile (M\(_4\) > M\(_1\), M\(_3\) > M\(_2\) ) was different from hexahydro-sila-difenidol. Replacement of the centrat silicon atom of hexahydro-sila-difenidol, p-fluoro-hexahydro-sila-difenidol and thdr quatemary (N-methylated) analogues by a carbon atom did not change their binding affinities significantly. The iour muscarinic receptors showed a higher affinity for the (R)- than for the (S)-enantiomers of hexahydro-difenidol, p-fluorohexahydro-difenidol and their methiodides. The stereoselectivity varied depending on the receptor subtype and drug considered. KW - Anorganische Chemie KW - Muscarinic receptor antagonists (selective) KW - Hexahydro-sila-difenidol analogues KW - p-Fluoro-hexahydro-sila-difenidol KW - Stereoselectivity Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64128 ER - TY - JOUR A1 - Waelbroeck, M. A1 - Camus, J. A1 - Tastenoy, M. A1 - Mutschler, E. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Lambrecht, G. A1 - Christophe, J. T1 - Stereoselectivity of (R)- and (S)-hexahydro-difenidol binding to neuroblastoma M\(_1\), cardiac M\(_2\), pancreatic M\(_3\), and striatum M\(_4\) muscarinic receptors N2 - (R)-Hexahydro-difenidol has a higher affinity for M\(_1\) receptors in NB-OK 1 cells, pancreas M\(_3\) and striatum M\(_4\) receptors (pKi 7.9 to 8.3) than for cardiac M2 receptors (pKi 7 .0). (8)-Hexahydro-difenidol, by contrast, is nonselective (pKi 5.8 to 6.1). Our goal in the present study was to evaluate the importance ofthe hydrophobic phenyl, and cyclohexyl rings of hexahydro-difenidol for the stereoselectivity and reeeptor selectivity of hexahydro-difenidol binding to the four muscarinic receptors. Our results indieated that replacement of the phenyl ring of hexahydro-difenidol by a cyclohexyl group <~ dicyclidol) and ofthe cyclohexyl ring by a phenyl moiety <~ difenidol) indueed a !arge (4- to 80-fold) decrease in binding affinity for all musearlnie receptors. Difenidol had a signifieant preference for M\(_1\) , M\(_3\) , and M\(_4\) over M\(_2\) receptors; dicyclidol, by eontrast, had a greater affinity for M\(_1\) and M\(_4\) than for M\(_2\) and M\(_3\) receptors. The binding free energy deerease due to replacement ofthe phenyl and the cyelohexyl groups of(R)-hexahydro-difenidol by, respectively, a eyclohexyl and a phenyl moiety was almostadditive in the ease of M\(_4\) (striatum) binding sites. In the ease ofthe cardiac M\(_2\), pancreatic M\(_3\) , or NB-OK 1 M\(_1\) receptors the respective binding free energies were not eompletely additive. These results suggest that the four (R)-hexahydro-difenidol ''binding moieties" (phenyl, cyclohexyl, hydroxy, and protonated amino group) cannot simultaneously form optimal interaetions with the M\(_1\), M\(_2\), and M\(_3\) muscarinic receptors. When eaeh of the hydrophobic groups is modified, the position of the whole molecule, relative to the four subsites, was changed to allow an optimal overall interaction with the musearlnie receptor. KW - Anorganische Chemie KW - hexahydro-difenidol enantiomers KW - muscarinic receptor subtypes KW - stereoselective interaction KW - difenidol KW - dicyclidol Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64135 ER - TY - JOUR A1 - Waelbroeck, M. A1 - Camus, J. A1 - Tastenoy, M. A1 - Feifel, R. A1 - Mutschler, E. A1 - Tacke, R. A1 - Strohmann, C. A1 - Rafeiner, K. A1 - Rodrigues de Miranda, J. F. A1 - Lambrecht, G. T1 - Binding and functional properties of hexocyclium and sila-hexocyclium derivatives to muscarinic receptor suhtypes JF - British Journal of Pharmacology N2 - 1 We have compared the binding properties of several hexocyclium and sila-hexocyclium derivatives to muscarinic Ml receptors (in rat brain, human neuroblastoma (NB-OK I) cells and calf superior cervical ganglia), rat heart M2 receptors, rat pancreas M3 receptors and M4 receptors in rat striatum, with their functional antimuscarinic properties in rabbit vas deferens (Ml/M4-like), guinea-pig atria (M2), and guinea-pig ileum (M3) muscarinic receptors. 2 Si la-substitution (C/Si exchange) of hexocyclium (~ sila-hexocyclium) and demethyl-hexocyclium (~demethyl-sila-hexocyclium) did not significantly affect their affinities for muscarinic receptors. By contrast, sila-substitution of demethoxy-hexocyclium increased its affinity 2 to 3 fold for all the muscarinic receptor subtypes studied. 3 The p-fluoro- and p-chloro-derivatives of sila-hexocyclium had lower affinities than the parent compound at the four receptor subtypes, in binding and pharmacological studies. 4 In binding studies, o-methoxy-sila-hexocyclium (Ml = M4 ~ M3 ~ M2) had a much lower affinity than sila-hexocyclium for the four receptor subtypes, and discriminated the receptor subtypes more poorly than sila-hexocyclium (Ml = M3> M4> M2)' This is in marked contrast with the very clear selectivity of demethoxy-sila-hexocyclium for the prejunctional MtlM4-like heteroreceptors in rabbit vas deferens. 5 The tertiary amines demethyl-hexocyclium, demethyl-sila-hexocyclium and demethyl-o-methoxy-silahexocyclium had 10 to 30 fold lower affinities than the corresponding quaternary ammonium derivatives. KW - Hexocyclium/sila-hexocyclium derivatives KW - o-methoxy-sila-hexocyclium KW - muscarinic receptor subtypes KW - structure/ affinity relationships KW - binding/functional correlations KW - muscarinic receptor antagonists Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128265 VL - 112 ER - 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 - 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 - Lange, H. A1 - Attar-Bashi, M. T. T1 - Baseninduzierte 1,2-Hydridverschiebungen vom Silicium zum Kohlenstoff: "Anomale" Substitutionsreaktionen an (Halogen-methyl)diorganylsilanen T1 - Base Induced l,2-Hydride Shifts from Silicon to Carbon: "Anomalous" Substitution Reactionswith (Halomethyl)diorganosilanes N2 - (C\(_6\)H\(_5\))\(_2\)Si(H)CH\(_2\)X (1 a: X = Cl; 1 b: X = I) und C\(_6\)H\(_5\)(CH\(_3\))Si(H)CH\(_2\)CI (10) reagieren mit LiOCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\) (2b) zu den Alkoxysilanen (C\(_6\)H\(_5\))\(_2\)Si(CH\(_3\))OCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\) (5) bzw. C\(_6\)H\(_5\)(CH\(_3\))\(_2\)SiOCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\) (12). Die Bildung dieser unerwarteten Reaktionsprodukte wird durch einen nucleophilen Angriff des Alkoxids am Si-Atom gedeutet. dem sich eine intramolekulare 1 ,2-Hydridverschiebung vom Si zum C und Eliminierung von Cl e anschließt. Mit weichen Basen, wie z. B. I (-) und (-)SCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\), wurden dagegen "normale" Substitutionsreaktionen am C-Atom der SiCH\(_2\)Cl-Gruppe beobachtet N2 - (C\(_6\)H\(_5\))\(_2\)Si(H)CH\(_2\)X (Ia: X = Cl; 1 b: X = I) and C\(_6\)H\(_5\)(CH\(_3\))Si(H)CH\(_2\)CI (10) react with LiOCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\) (2b) to give the alkoxysilanes (C\(_6\)H\(_5\))\(_2\)Si(CH\(_3\))OCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\) (5) and C\(_6\)H\(_5\)(CH\(_3\))\(_2\)SiOCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\) (12), respectively. The formation of these unexpected reaction products is interpreted by a nucleophilic attack of the alkoxide at the Si atom, followed by an intramolecular 1 ,2-hydride shift from Si to C and elimination of Cl 8. However, with soft bases [for example l e and (-)SCH\(_2\)CH\(_2\)N(CH\(_3\))\(_2\) "normal" substitution reactions at the C atom of the SiCH\(_2\)Cl group were observed. KW - Anorganische Chemie Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63734 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 - Eltze, M. A1 - Ullrich, B. A1 - Mutschler, E. A1 - Moser, U. A1 - Bungardt, E. A1 - Friebe, T. A1 - Gubitz, C. A1 - Tacke, Reinhold A1 - Lambrecht, G. T1 - Characterization of muscarinic receptors mediating vasodilation in rat perfused kidney N2 - The muscarinic receptor mediating vasodilation of resistance vessels in the rat isolated, constant-pressure perfused kidney (preconstriction by w- 7 M cirazoline) was characterized by subtype-preferring agonists and se]ective antagonists. The agonists produced vasodi1ation with the fol1owing rank order of potency: arecaidine propargy] ester (APE) > 5-methylfurtrethonium = methacholine = oxotremorine > (S)-aceclidine > arecaidine 2-butyne-1,4-diyl bisester > 4-Cl-McN-A-343 = (R)-nipecotic acid ethyl ester = N-ethyl-guvacine propargyl ester- (R)-aceclidine = (S)-nipecotic acid ethyl ester > McN-A-343. Agonist-induced vasodilation disappeared after destruction of the endothelium with detergent. Highly significant correlations of agonist potencies for vasodilation were found between rat kidney and guinea-pig ileum submucosal arterioles as weH as agonist potencies at smooth muscle muscarinic M\(_3\) receptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-Nmethylpiperidine methiodide (4-DAMP) > (R)-hexahydro-difenidol - hexahydro-sila-difenidol > pirenzepine - p-fluorohexahydro- sila-difenidol- himbacine- AF-DX 384- AQ-RA 741 > (S)-hexahydro-difenidol) to attenuate vasodilation to APE in rat kidney, correlated significantly with affinities at M\(_3\) receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M\(_1\) and M\(_2\) receptors in rabbit vas deferens. The agonist and antagonist potencies suggest that vasodilation elicited by muscarinic stimuli in endothelium-intact rat renal vasculature is mediated by functional muscarinic M\(_3\) receptors. KW - Anorganische Chemie KW - Kidney (perfused KW - rat) KW - Muscarinic receptor agonists KW - Muscarinic receptor antagonists KW - Arterioles (submucosal) KW - Ileum; Atrium KW - Vas deferens Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64283 ER - TY - JOUR A1 - Mühleisen, M. A1 - Tacke, Reinhold T1 - Twofold deprotonated citric acid as a bidentate ligand of pentacoordinate silicon: synthesis and structural characterization of the zwitterionic \(\lambda_5\)Si-spirosilicate bis[citrato(2-)-O\(^3\),O\(^4\)][(dimethylammonio)methyl]silicate hydrate N2 - The zwitterionic \(\lambda_5\) Si-spirosilicate bis[ citrato(2-)-0\(^3\) ,0\(^4\) )[ ( dimethylammonio) methyl]silicate (4) was synthesized by reaction of (MeO)\(_3\)SiCH\(_2\)NMe\(_2\) (3) with citric acid (molar ratio 1 :2) in acetonitrile at room temperature and isolated, after crystallization from water, as the hydrate 4 · H\(_2\)O (yield 81 %). The crystal structure of 4 · H\(_2\)O was studied by single-crystal X-ray diffraction. The alcoxide oxygen atoms and central carboxylate oxygen atoms of two citrato(2-) ligands and one carbon atom coordinate to the silicon atom of 4 · H\(_2\)O. The coordination polyhedron around the pentacoordinate silicon atom (SiO\(_4\)C framework) can be described as a distorted trigonal bipyramid, the two carboxylate oxygen atoms occupying the axial sites. The \(\lambda_5\) Si~silicon(IV) complex 4 also exists in solution (DMSO, H\(_2\)O). KW - Anorganische Chemie KW - Silicon KW - pentacoordinate KW - Lambda5Si-Spirosilicate KW - zwitterionic KW - Citrato(2-)-03 KW - 04ligand Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64388 ER - TY - JOUR A1 - Mühleisen, M. A1 - Tacke, Reinhold T1 - meso-[1,4-Piperaziniumdiylbis(methylene)]bis{bis[2-methyllactato(2-)-O1,O2]silicate} octahydrate: synthesis and crystal structure analysis of a zwitterionic dispirocyclic \(\lambda^5\)Si,\(\lambda^5\)Si'-disilicate N2 - The zwitterionic dispirocyclic \(\lambda^5\)Si,\(\lambda^5\)Si'-disilicate meso-[1 ,4-piperaziniumdiylbis( methylene)]bis{ bis[ 2-methyllactato(2-)-O\(^1\),O\(^2\)]silicate} octahydrate (6-8H\(_2\)O) was synthesized by reaction of 1,4-bis[(trimethoxysilyl}methyl] piperazine (8) with 2-methyllactic acid (molar ratio 1:4) in water/acetone (yield 82%). The molecular dinuclear silicon(IV) complex 6 contains two pentacoordinate (formally negatively charged) silicon atoms and two tetracoordinate (formally positively charged) nitrogen atoms. The crystal structure of 6•8H20 was studied by X-ray diffraction. KW - Anorganische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64396 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Mühleisen, M. T1 - Bis[benzilato(2-)-O\(^1\),O\(^2\)][2-(dimethylammonio)ethoxy]silicate: synthesis and structural characterization of a zwitterionic \(\lambda^5\)Si-silicate with a SiO\(_5\) framework N2 - No abstract available KW - Anorganische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64400 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Pikies, J. A1 - Wiesenberger, F. A1 - Ernst, L. A1 - Schomburg, D. A1 - Waelbroeck, M. A1 - Christophe, J. A1 - Lambrecht, G. A1 - Gross, J. A1 - Mutschler, E. T1 - Sila-biperiden und endo-Sila-biperiden: Synthesen, Kristallstrukturen und antimuscarinische Eigenschaften N2 - Starting from trichloro(vinyl)silane (Cl\(_3\)SiCH=CH\(_2\)), the musearinic antagonists sila-biperiden [rac-(SiRS,C2SR>-ao-2] and endosila- biperiden [rac-(SiRS,C2SR)-endo-2] were prepared by a seven-step synthesis. Both silanols are configurationally stableininert organic solvents but undergo slow epimerization in aqueous solution (pH 7.4, 32°C) by inversion of the configuration at the silicon atom. The relative configurations of sila-biperiden and endo-sila-biperiden were detennined by single-crystal X-ray diffraction. Both compounds form intennolecular 0-H · · · N hydrogen bonds in the crystal leading to the fonnation of centrosymmetric dimers (sila-biperiden) and infinite chains (endo-sila-biperiden), respectively. Sila-biperiden is a silicon analogue (C/Si exchange) of the antiparkinsonian drug biperiden [rac-(CRS/C2SR}-exo-1]. In functional phannacological experiments, as well as in radioligand competition studies, biperiden, sila-biperiden and endo-sila-biperiden behaved as simple competitive antagonists at muscarinic Ml-, M2-, M3- and M4-receptors. The three compounds displayed the highest affinity for Ml-receptors (pA\(_2\) values: 8.72-8.80; pK\(_i\) values: 8.8-9.1), intermediate affinity for M4- and M3-receptors, and lowest affinity for M2-receptors (pA\(_2\) values: 7.57-7.79; pK\(_i\) values: 7.7-7.8). The affinity profile (Ml >. M4 > M3 > M2) of biperiden, sila-biperiden and endo-sila-biperiden is qualitatively similar to that of the M1-selective muscarinic antagonist pirenzepine. The antimuscarinic properlies of the C/Si analogues biperiden and sila-biperiden are almost identical. N2 - Die Antimuscarinica Sila-biperiden [rac-(SiRS,C2SR)-exo-2] und endo-Sila-biperiden [rac-(SiRS,C2SR)-endo-2] wurden ausgehend von Trichlor(vinyl)silan (Cl\(_3\)SiCH=CH\(_2\)) durch eine siebenstufige Synthese dargestellt. Die beiden Silanoie sind in inerten organischen Solvenzien konfigurationsstabil, unterliegen aber in wässeriger Lösung (pH 7.4, 3ZOC) einer Epimerisierung durch Inversion der Konfiguration am Silicium-Atom. Die relativen Konfigurationen von Sila-biperiden und endo-Sila-biperiden wurden durch Einkristall-Röntgenstrukturanalysen bestimmt. Beide Verbindungen bilden im Kristall intermolekulare 0-H · · · N-Wasserstoff- Brückenbindungen aus, die zum Aufbau von zentrosymmetrischen Dimeren (Sila-biperiden) bzw. unendlichen Ketten (endo-Sila-biperiden) führen. Sila-biperiden ist ein Silicium-Analogon (C/Si-Austausch) des Antiparkinsonmittels Biperiden [rac-(CRS,C2SR>-ao-1). Sowohl in funktionellen pharmakologischen Untersuchungen als auch in Radioligand-Kompetitionsexperimenten erwiesen sich Biperiden, Sila-biperiden und endo-Sila-biperiden als rein kompetitive Antagonisten an muscarinischen M1-, M2-, M3- und M4-Rezeptoren. Alle drei Verbindungen zeigten die höchste Affinität zu den Mt-Rezeptoren (pA\(_2\)-Werte: 8.72-8.80; pKrWerte: 8.8-9.1), eine deutlich geringere Affinität zu den M4- und M3-Rezeptoren und die niedrigste Affinität zu den kardialen M2-Rezeptoren (pA\(_2\)-Werte: 7.57-7.79; pKi-Werte: 7.7-7.8). Das Affinitätsprofil (Ml > M4 > M3 > M2) von Biperiden, Sila-biperiden und endo-Sila-biperiden ist dem des Mt-selektiven Antimuscarinicums Pirenzepin qualitativ sehr ähnlich. Die antimuscarinischen Eigenschaften der C/Si-Analoga Biperiden und Sila-biperiden sind nahezu identisch. KW - Anorganische Chemie KW - Silicon KW - Silanol KW - Sila-biperiden KW - Bioorganosilicon chemistry KW - Muscarinic antagonist KW - Muscarinic receptor subtype Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64303 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Mühleisen, M. A1 - Jones, P. G. T1 - Das erste zwitterionische, optisch aktive Disilicat mit pentakoordiniertem Silicium N2 - No abstract available KW - Anorganische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64343 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Mühleisen, M. A1 - Jones, P. G. T1 - The first zwitterionic, optically active disilicate with pentacoordinate silicon N2 - No abstract available KW - Anorganische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64358 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Mühleisen, M. T1 - Hexakoordiniertes Silicium in einer molekularen Verbindung mit einer F\(_5\)SiC-Einheit N2 - No abstract available KW - Anorganische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64365 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Mühleisen, M. T1 - Hexacoordinate silicon in a compound with an F\(_5\)SiC unit N2 - No abstract available KW - Anorganische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64378 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Link, M. A1 - Zilch, H. T1 - Eine neue in situ-Darstellung von (Trimethyl-silyl)trifluormethansulfonat durch thermisch induzierte Umlagerung T1 - A New in situ Preparation of Trimethylsilyl Trifluoromethanesulfonateby Thermally Induced Rearrangement N2 - A new in situ preparation of trimethylsilyl trifluoromethanesulfonate (3) is described: 3 is generated by a thermally induced rearrangement of (dimethylsilyl)methyl trifluoromethanesulfonate (2), which can be prepared by reaction of (CH\(_3\))\(_2\)Si(H)CH\(_2\)OH (1) with (CF\(_3\)SO\(_2\))\(_2\)O. Starting with C\(_6\)H\(_5\)(CH\(_3\))Si(H)CH\(_2\)OH (5), the derivative (methylphenylsilyl)methyl trifluoromethanesulfonate (6) can be obtained by a similar method. Its thermally induced rearrangement Ieads to dimethylphenylsilyl trifluoromethanesulfonate (7). The rearrangements 2---> 3 and 6---> 7 were found to be first-order reactions with half-lifes at 80 oc of 0.75 and 1.7 h, respectively. KW - Anorganische Chemie Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63784 ER - TY - JOUR A1 - Schomburg, D. A1 - Link, M. A1 - Linoh, H. A1 - Tacke, Reinhold T1 - Molekülstruktur der Akarizide Chlortrineophylstannan, Chlortris[(dimethylphenylsilyl)methyl]stannan und Trineophyl(1,2,4-triazol-1-yl)stannan-hemihydrat sowie des 2,5-Dimethyl-2,5-diphenylhexans (Bineophyl) N2 - Die Kristall- und Molekülstrukturen der Akarizide Chlortrineophylstannan (Ia), Chlortris[ ( dimethylphenylsilyl)methyl]stannan (tb) und Trineophyl(1,2,4-triazol-1- yl)stannan-hemihydrat (2a · 0.5H\(_2\)0) wurden durch Einkristall-Röntgenstrukturanalysen bestimmt. Zu V ergleichszwecken wurde ausserdem die Struktur des 2,5-Dimethyl-2,5-diphenylhexans (Bineophyl, 4) untersucht. Die Knüpfung von drei sehr raumerfüllenden N eophyl-Resten an ein Zinnatom führt zu einer deutlichen Verzerrung der tetraedrischen Geometrie [ta: C-Sn-C 117.2°, C-Sn-Cl99.7°; 2a·0.5H20: C-Sn-C 116.9° (Mittelwert), C-Sn-N 100.2° (Mittelwert)]. Austausch der zentralen Kohlenstoffatome in den Neophyt-Substituenten von la durch Siliciumatome führt zu einer Verringerung des Raumbedarfs und dadurch zu einer erkennbaren Angleichung an die tetraedrische Geometrie [lb: C-Sn-C 113.3° (Mittelwert), C-Sn-Cl 105.3° (Mittelwert)]. N2 - The crystal and molecular structures of the acaricides chlorotrineophylstannane (ta), chlorotris[( dimethylphenylsilyl)methyl]stannane (tb ), and trineophyl(1,2,4-triazol- 1-yl)stannane hemihydrate (2a · 0.5H\(_2\)0), have been determined by single-crystal X-ray diffraction studies. The structure of 2,5-dimethyl-2,5-diphenylhexane (4) was also investigated for comparison. Binding of three very bulky neophyl ligands around tin causes serious distortion of the tetrahedral geometry [la: C-Sn-C 117.2°, C-Sn-Cl 99.7°; la · 0.5H20: C-Sn-C 116.9° (mean), C-Sn-N 100.2° (mean)]. Replacement of the central carbon atoms in the neophyl substituents of ta by silicon atoms Ieads to a decrease in steric strain and hence to a much smaller distortion of the tetrahedral geometry [lb: C-Sn-C 113.3° (mean), C-Sn-Cl105.3° (mean)]. KW - Anorganische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63840 ER - TY - JOUR A1 - Polidori, C. A1 - Massi, M. A1 - Lambrecht, G. A1 - Mutschler, E. A1 - Tacke, Reinhold A1 - Melchiorre, C. T1 - Selective antagonists provide evidence that M\(_1\) muscarinic receptors may mediate carbachol-induced drinking in the rat N2 - The present study served to investigate the ability of seven selective muscarinic antagonists to inhibit carbachol-induced drinking in the rat. The muscarinic antagonists were given by intracerebroventricular (i.c.v.) injection 1 min before the i.c.v. injection of carbachol (1 \(\mu\)g/rat). The M\(_2\) antagonist, methoctramine, was inactive up to 80.3 nmol/rat. The M\(_3\) antagonist, p-fluoro-hexahydro-sila-difenidol, elicited a modest (42%) but statistically significant inhibition of drinking only at 80 nmol/rat. On the other band, the selective M\(_1\) antagonists, (R)-trihexyphenidyl, o-methoxy-sila-hexocyclium and pirenzepine, produced a marked and dose-dependent inhibition of carbachol-induced drinking, their 1050 values being 0.51. 7.36 and 9.31 nmoljrat. Also the M\(_1\)/M\(_3\) antagonists, 4-diphenylacetoxy-Nmethylpiperidine methiodide and hexahydro-sila-difen.idol, were potent inhibitors of carbachol-induced drinking, their ID\(_50\) values (0.28 and 11.09 nmoljrat) being related to their pA\(_2\) values for M1 receptors in rabbi t vas deferens. These data suggest that carbachol-induced drinking may be mediated by activation of muscarinic M\(_1\) receptors. KW - Anorganische Chemie KW - Carbachol-induced drinking KW - Muscarinic receptor antagonists KW - Muscarinic receptor subtypes KW - Muscarinic M1 receptors; Muscarinic M2 receptors Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64044 ER - TY - JOUR A1 - Dörje, F. A1 - Wess, J. A1 - Lambrecht, G. A1 - Tacke, Reinhold A1 - Mutschler, E. A1 - Brann, M. R. T1 - Antagonist binding profiles of five cloned human muscarinic receptor subtypes N2 - A variety of muscarinic antagonists are currently used as tools to pharmacologically subclassify muscarinic receptors into M\(_1\), M\(_2\) and M\(_3\) subtypes. ln the present study I we have determined the affinity proflies of several of these antagonists at five cloned human muscarinic receptors (m1-m5) stably expressed in Chinesehamster ovary cells (CHO-K1). At all five receptorsl the (R)-enantiomers of trihexyphenidyl and hexbutinol displayed considerably higher affinities (up to 525-fold) than their corresponding (S)-isomers. The stereoselectivity ratios [inhibition constant( S)/inhibition constant(R)] for both pairs of enantiomers were lowest at m2 receptors, suggesting that less stringent configurational demands are made by this receptor subtype. The "M\(_1\)-selective" antagonist (R)-trihexyphenidyl displayed high affinities for m1 and m4 receptors. The "M\(_2\)-selective" antagonists himbacinel (±}-5, 11-dihydro-11-1[(2-[(dipropylamino)methyl]-1- piperidinyllethyl)amino]carbonyii-6H-pyrido(213-b)(1 ~4)benzodiazepine- 6-one (AF-DX 384)1 11-(14-[4-(diethylamino)butyl)-1-piperidinyll acetyl)-5~ 11-dihydro-6H-pyrido(2~3-b) (1~4)benzodiazepine-6-one (AQ-RA 741) and (+K11-(12-[(diethylamino)methyl]-1-piperidinyll acetyl)-5~ 11-di-hydro-6H-pyrido(2~3-b)(1,4)benzodiazepine-6-one (AF-OX 250; the (+)-enantiomer of AF-DX 116] exhibited high affinities for m2 and m41 intermediate affinities for m1 and m3 and low affinities for m5 receptors. This selectivity profile was most prominent for AQ-RA 7 41 I which displayed 195- and 129-fold higher affinities for m2 and m4 receptors than for mS receptors. The "M\(_3\)-selective" antagonist (±)-p-fluoro-hexahydro-sila-difenidol hydrochloride (pFHHsiD) exhibited high affinity for m1 I m3 and m4 receptors. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) bound with up to 7 -fold higher affinities to m1 I m31 m4 and m5 receptors than to m2 receptors. Although none of the tested antagonists showed more than 2-fold selectivity for one subtype over all other subtypes, each receptor displayed a unique antagonist binding profile. KW - Anorganische Chemie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64113 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Wiesenberger, F. A1 - Becker, B. A1 - Rohr-Aehle, R. A1 - Schneider, P. B. A1 - Ulbrich, U. A1 - Sarge, S. M. A1 - Cammenga, H. K. A1 - Koslowski, T. A1 - Niessen, W. von T1 - Ester von (Hydroxymethyl)diorganylsilanen: Synthese und thermisch induzierte Umlagerung T1 - Esters of (Hydroxymethyl)diorganylsllanes: Synthesis and Thermally Induced Rearrangement N2 - Twenty silanes of the type R\(^1\)R\(^2\)Si(H)CH\(_2\)OR\(^3\) (A) were syn- and entropy of activation) of these reactions were studied by thesized {R\(^1\), R\(^2\) = Me, Ph, 1-naphthyl, PhCH\(_2\), Me\(_3\)SiCH\(_2\); OR\(^3\) means of düferential scanning calorimetry (DSC). In addition, = OC(O)Me, OC(O)Ph, OC(O)CF\(_3\) , OS(0)\(_2\)CF\(_3\), OP(O)Ph\(_2\), the kinetics of all reactions were investigated by 1H-NMR OC(O)Cl, and studied for their thermal behaviour. The silanes spectroscopy. The transition state of the rearrangement was A undergo a thermally induced rearrangement to give the investigated by an ab initio study based on the model comcorresponding silanes R\(^1\)R\(^2\)Si(OR\(^3\))Me (B). For compounds with pound H\(_3\)SiCH\(_2\)OC(O)H (-> MeH\(_2\)SiOC(O)H]. The theoretical OR3 = OC(O)Cl, an additional decarboxylation takes place to data and the experimentally obtained energetic and kinetic yield the chlorosilanes R1R2Si(Cl)Me. Except for the deriva- data are discussed in terms of mechanistic aspects of the retives with OR\(^3\) = OC(O)Cl, the energetic (reaction enthalpy) arrangement reaction A -> B. and kinetic data (reaction order, frequency factor, enthalpy ... KW - Anorganische Chemie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64188 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 - TY - JOUR A1 - Eltze, M. A1 - Gmelin, G. A1 - Wess, J. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Mutschler, E. A1 - Lambrecht, G. T1 - Presynaptic muscarinic receptors mediating inhibition of neurogenic contractions in rabbit vas deferens are of the ganglionic M\(_1\)-type N2 - The present study was designed to further charaeterize the presynaptie musearlnie M\(_1\)-reeeptor responsible for the inhibition of neuragenie eontraetions in the isolated rabbit vas deferens. Eleetrically induced twiteh eontraetions of this preparation were inhibited by the M\(_1\)-agonist, MeN-A-343, and by some of its analogs: 4-ehloro-phenyl derivative> MeN-A-343 > trans-olefinie analog> cis-olefinie analog. The same rank order of potency was observed for these agonists to raise the blood pressure of pithed rats by stimulation of M\(_1\)-receptors in sympathetie ganglia. A highly signifieant eorrelation was found between the antimusearinie potencies of atropine, pirenzepine and a series of 9 antagonists strueturally related to the ganglionie M\(_{1\beta}\)-receptor selective compounds, hexocyclium and hexahydro-difenidol, to antagonize the MeN-A-343-indueed inhibition of twitch eontraetions in rabbit vas deferens or the musearine-indueed depolarization in rat isolated superior eerVieal ganglia. It is suggested that the presynaptie musearlnie receptor that mediates inhibition of neuragenie contraetions in rabbit vas deferens is of the ganglionic M\(_{1\beta}\)-type. KW - Anorganische Chemie KW - Musearlnie aeetyleholine receptor antagonists KW - McN-A-343 analogs KW - Musearlnie receptor subtypes KW - Vas deferens (rabbit) KW - Pithed rat KW - Ganglia (rat) KW - Musearlnie aeetyleholine receptor agonists Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63912 ER - TY - JOUR A1 - Pfeiffer, A. A1 - Hanack, C. A1 - Kopp, R. A1 - Tacke, R. A1 - Moser, U. A1 - Mutschler, E. A1 - Lambrecht, G. A1 - Herawi, M. T1 - Human Gastric Mucosa Expresses Glandular M3 Subtype of Muscarinic Receptors JF - Digestive Diseases and Sciences N2 - Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 ± 6 fmol/mg protein and the tritiated ligand N-methylscopolamine had an affinity of (Kn) 0.39 ± 0.08 nM (n = 11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF-DX 116 had low affinities of 148 ± 32 nM (n = 13) and 4043 ± 1011 nM (n = 3) K n , respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities ofKn 78 ± 23 nM (n = 5) and 5.6 ± 1.8 nM (n = 3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type. KW - glandular M3 receptor KW - acid secretion KW - muscarinic receptor subtype KW - human gastric mucosa KW - stomach Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128286 VL - 35 IS - 12 ER - TY - JOUR A1 - Tacke, M. A1 - Schuberth, W. A1 - Becker, Charles R. A1 - Haas, L. D. T1 - The dielectric constant of PbTe at 4.2 K and \(\tilde ν\)=84.15 cm\(^{-1}\), 96.97 cm\(^{-1}\), 103.60 cm\(^{-1}\) N2 - The dielectric constant of a PbTe epitaxial layer has been measured by surface wave spectroscopy using an optically pumped far-infrared laser and the technique of attenuated total reflection. Y1 - 1982 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30821 ER - TY - JOUR A1 - Tacke, Reinhold A1 - Saad, S. M. T1 - Silylation of cellulose N2 - Ethane-l:2-diol and propane-l:3-diol reaet with 1: 1:3:3-tetramethyl-l:3-dichlorodisiloxane forming the corresponding rings. However, no ring compounds could be traced tbrough the reaction between butane-l :4-diol, glycerol and the dichlorodisiloxane respectively, where only polymeric compounds are formed. The silylation products of the di- and trihydroxy alcohols, as model compounds, has confirmed that the ring formation during silylation of cellulose with dichlorodisiloxane is uncertain. KW - Anorganische Chemie Y1 - 1977 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78368 ER - TY - JOUR A1 - Saad, S. M. A1 - Tacke, Reinhold T1 - Zur Darstellung von 1,1,3,3-Tetramethyl-1,3-disila-2,4,7-trioxa-cycloheptan (1) und 1,1,3,3-Tetramethyl-1,3-disila-2,4,8-trioxa-cyclooctan (2) N2 - No abstract available. KW - Anorganische Analyse Y1 - 1977 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86958 ER -