@article{FeifelWagnerRoederStrohmannetal.1990,
  author    = {Feifel, R. and Wagner-R{\"o}der, M. and Strohmann, C. and Tacke, Reinhold and Waelbroeck, M. and Christophe, J. and Mutschler, E. and Lambrecht, G.},
  title     = {Stereoselective inhibition of muscarinic receptor subtypes by the enantiomers of hexahydro-difenidol and acetylenic analogues},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64002},
  year      = {1990},
  abstract  = {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.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{DoerjeWessLambrechtetal.1991,
  author    = {D{\"o}rje, F. and Wess, J. and Lambrecht, G. and Tacke, Reinhold and Mutschler, E. and Brann, M. R.},
  title     = {Antagonist binding profiles of five cloned human muscarinic receptor subtypes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64113},
  year      = {1991},
  abstract  = {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.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{TackeWiesenbergerBeckeretal.1992,
  author    = {Tacke, Reinhold and Wiesenberger, F. and Becker, B. and Rohr-Aehle, R. and Schneider, P. B. and Ulbrich, U. and Sarge, S. M. and Cammenga, H. K. and Koslowski, T. and Niessen, W. von},
  title     = {Ester von (Hydroxymethyl)diorganylsilanen: Synthese und thermisch induzierte Umlagerung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64188},
  year      = {1992},
  abstract  = {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 d{\"u}ferential 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 ...},
  subject      = {Anorganische Chemie},
  language  = {de}
}
@article{BungardtVockertFeifeletal.1992,
  author    = {Bungardt, E. and Vockert, E. and Feifel, R. and Moser, U. and Tacke, Reinhold and Mutschler, E. and Lambrecht, G. and Suprenant, A.},
  title     = {Characterization of muscarinic receptors mediating vasodilation in guinea-pig ileum submucosal arterioles by the use of computer-assisted videomicroscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64206},
  year      = {1992},
  abstract  = {Muscarinic receptors of rcsistance vessels (submucosal artcrioles, outside diametcr 50-75 J,Lm) from the guinea-pig small intestinc were invcstigatcd in vitro using a computcr-assisted vidcomicroscopy system (Diamtrak <~t ). The muscarinic receptor which mediates vasodilation of prccontractcd [U-46619 (300 nM) or (- )-noradrcnaline (1 0 J.L M)] artcriolcs was characterized with scveral muscarinic agonists and subtypc-sclectivc antagonists. Thc following agonists all produccd cquivalent maximum vasodilation (given in rank ordcr of potency): acctylcholinc = arccaidinc propargyl cstcr (APE) > oxotremorine = ( ± )-muscarinc = ( ± )-mcthacholinc > carbachol > 4-[[N-{4-chlorophenyl)carbamoyl]oxy]-2-hutynyltrimcthylammonium iodide (4-CI-McN-A- 343). 4-([N-(3-ChlorophcnyD-carbamoyl)oxy]-2-butynyltrimcthylammonium chloride (McN-A-343) and N-ethyl-guvacinc propargyl ester (NEN-APE) produccd minimal or no artcriolar vasodilation. Thc muscarinic antagonists pircnzcpinc, ( ± )-5,11-dihydro-11- [[[2-[2-((dipropylamino)methyl}-1-pipcridinyl]ethyl]amino ]-carbonyi]-6H-pyrido(2,3-h)( 1 ,4)-benzodiazcpin-6-onc (AF-DX 384 ), 11- [[ 4-[4-(dicthylamino)butyl]-1-piperidinyl]acetyl]-5, ll-dihydro-6H-pyrido(2.3-h)( 1,4 )-bcnzodiazepin-6-onc (AQ-RA 741 ), p-fluorohexahydro- sila-difcnidol (p-F-HHSiD), 4-diphcnylacetoxy-N-methylpipcridine mcthiodidc (4-DAMP) and (R)- and (S)hexahydro- difcnidol [(R)-HHD, (S)-HHD] shifted thc muscarinc, mcthacholinc or carbachol dosc-rcsponsc curve to the right in a compctitive manner. Schildanalysis of the data yicldcd pA\(_2\) valucs for pircnzcpinc (6.74/6.9), AF-DX 384 (6.72), AQ-RA 741 (6.58), p-F-HHSiD (7.53/7.57), 4-DAMP (9.06), (R)-HHD (7.88/8.32) and (S)-HHD (5.52/5.88). Thus, it can he concluded that submucosal arteriolcs posscss only the M\(_3\) functional muscarinic reccptor, the activation of which causcs hlood vcsscl dilation. The preparation dcscribcd is considcrcd to be a valuable now bioassay for pharmacological investigations of drug actions at muscarinic receptors in the peripheral vascular system.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{TackeNiednerFrohneckeetal.1980,
  author    = {Tacke, Reinhold and Niedner, R. and Frohnecke, J. and Ernst, L. and Sheldrick, W. S.},
  title     = {Darstellung und Eigenschaften potentiell curarewirksamer Silicium-Verbindungen, II},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63670},
  year      = {1980},
  abstract  = {Die potentiell curarewirksamen Silicium-Verbindungen Sa, Sc, Sd, Sg, Sh und 9a-9d wurden dargestellt. \(^1\)H-NMR-spektroskopische Untersuchungen ergaben Informationen {\"u}ber die Konformationen von 5 a- Sc in L{\"o}sung. Die Kristall- und Molek{\"u}lstruktur von 5 c wurde r{\"o}ntgenstrukturanalytisch bestimmt. Die muskelrelaxierenden Eigenschaften von S a- 5 h und 9 a-9 d wurden vergleichend an der Maus (i.v., LD50-Werte) untersucht. Die ermittelten Struktur-WirkungsBeziehungen werden in Hinblick auf die unterschiedlichen kovalenten Radien des Kohlenstoffund Siliciumatoms und die hieraus resultierenden N ... N-Abst{\"a}nde diskutiert.},
  subject      = {Anorganische Chemie},
  language  = {de}
}
@article{TackeStreckerNiedner1981,
  author    = {Tacke, Reinhold and Strecker, M. and Niedner, R.},
  title     = {Cholinesterase-hemmende Organophosphors{\"a}ureester und ihre Sila-Analoga},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63689},
  year      = {1981},
  abstract  = {Die Organophosphors{\"a}ureester 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-Aktivit{\"a}t die gleichen Struktur-Wirkungs-Beziehungen wie die Silicium-Verbindungen 1 b- 4 b. Letztere sind jeweils wirksamer als die entsprechenden C-Analoga.},
  subject      = {Anorganische Chemie},
  language  = {de}
}
@article{TackeFrohneckeNiedner1982,
  author    = {Tacke, Reinhold and Frohnecke, J. and Niedner, R.},
  title     = {Darstellung und Eigenschaften potentiell curarewirksamer Silicium-Verbindungen, IV},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63711},
  year      = {1982},
  abstract  = {Die Synthese der Organosilicium· Verbindungen 3 a- d wird erstmalig beschrieben. Sie wurden durch ihre physikalischen, chemischen und pharmakologischen Eigenschaften charakterisiert. Ja- d wirken als uKurzzeit-Muskelrelaxantien", deren Entgiftung durch Hydrolyse der Si- OeBindungen (Sollbruchstellen) erfolgt.},
  subject      = {Anorganische Chemie},
  language  = {de}
}
@article{LambrechtFeifelForthetal.1988,
  author    = {Lambrecht, G. and Feifel, R. and Forth, B. and Strohmann, C. and Tacke, Reinhold and Mutschler, E.},
  title     = {p-Fluoro-hexahydro-sila-difenidol: the first M\(_{2\beta}\)-selective muscarinic antagonist},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63872},
  year      = {1988},
  abstract  = {No abstract available},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{TackeRohrAehle1988,
  author    = {Tacke, Reinhold and Rohr-Aehle, R.},
  title     = {Ester des (Hydroxymethyl)[(trimethylsilyl)methyl]silans: Synthese und thermisch induzierte Umlagerung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63889},
  year      = {1988},
  abstract  = {Die Synthese des (Hydroxymethyl)[(trimethylsilyl)methyl]silans (3) sowie des hiervon abzuleitenden Acetats 4 und Chlorformiats 6 wird beschrieben. 4 und 6 unterliegen einer thermisch induzierten Umwandlung zu den difunktionellen Silanen 5 bzw. 8. Die Umwandlungen 4 -> 5 und 6 -> 8 erfolgen gem{\"a}ß einer Kinetik 1. Ordnung mit Halbwertszeiten von 10.0 bzw. 3.6 h (135 ° C, in C\(_6\)D\(_6\)).},
  subject      = {Anorganische Chemie},
  language  = {de}
}
@article{PfeifferRochlitzNoelkeetal.1990,
  author    = {Pfeiffer, A. and Rochlitz, H. and Noelke, B. and Tacke, R. and Moser, U. and Mutschler, E. and Lambrecht, G.},
  title     = {Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type},
  series = {Gastroenterology},
  volume    = {98},
  journal   = {Gastroenterology},
  number    = {1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128337},
  pages     = {218-222},
  year      = {1990},
  abstract  = {Five subtypes of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of these antagonists was determined by radioligand binding experiments. In addition, their inhibitory potency on carbachol-stimulated inositol phosphate production was investigated. Inhibition of carbachol-stimulated aminopyrine uptake was used as an indirect measure of proton production. Both M3 antagonists, hexahydrosiladifenidol and silahexocyclium, had nanomolar affinities for parietal cell muscarinic receptors and potently antagonized inositol phosphate production with nanomolar Ki values. Silahexocyclium similarly antagonized aminopyrine accumulation while hexahydrosiladifenidol behaved as a noncompetitive antagonist. AF-DX 116 was a low-affinity ligand and a weak competitive antagonist at parietal-cell muscarinic receptors. It was concluded that muscarinic M3 receptors mediate acid secretion probably by activation of the phosphoinositide second messenger system in rat gastric parietal cells.},
  language  = {en}
}
@article{TackeStreckerSheldricketal.1979,
  author    = {Tacke, R. and Strecker, M. and Sheldrick, W. S. and Heeg, E. and Berndt, B. and Knapstein, K. M.},
  title     = {Sila-Pharmaka, 14. Mitt. Darstellung und Eigenschaften sowie Kristall-und Molek{\"u}lstruktur von Sila-Difenidol},
  series = {Zeitschrift f{\"u}r Naturforschung B},
  volume    = {34},
  journal   = {Zeitschrift f{\"u}r Naturforschung B},
  number    = {9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128391},
  pages     = {1279-1285},
  year      = {1979},
  abstract  = {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) {\AA}, 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 {\AA} is observed. The anticholinergic, histaminolytic and musculotropic spasmolytic activities of 6 a and 6 b are reported.},
  language  = {de}
}
@article{WaelbroeckCamusTastenoyetal.1993,
  author    = {Waelbroeck, M. and Camus, J. and Tastenoy, M. and Lambrecht, G. and Mutschler, E. and Kropfgans, M. and Sperlich, J. and Wiesenberger, F. and Tacke, R. and Christophe, J.},
  title     = {Thermodynamics of antagonist binding to rat muscarinic \(M_2\) receptors: antimuscarinics of the pridinol, sila-pridinol, diphenidol and sila-diphenidol type},
  series = {British Journal of Pharmacology},
  volume    = {109},
  journal   = {British Journal of Pharmacology},
  number    = {2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128439},
  pages     = {360-370},
  year      = {1993},
  abstract  = {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.},
  language  = {en}
}
@article{TackeSchuberthBeckeretal.1982,
  author    = {Tacke, M. and Schuberth, W. and Becker, Charles R. and Haas, L. D.},
  title     = {The dielectric constant of PbTe at 4.2 K and \(\tilde ν\)=84.15 cm\(^{-1}\), 96.97 cm\(^{-1}\), 103.60 cm\(^{-1}\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30821},
  year      = {1982},
  abstract  = {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.},
  language  = {en}
}
@article{TackeBentlagemTowartetal.1980,
  author    = {Tacke, Reinhold and Bentlagem, A. and Towart, R. and Meyer, H. and Bossert, F. and Vater, W. and Stoepe, K.},
  title     = {Sila-Analoga von Nifedipin-{\"a}hnlichen 4-Aryl-2.6-dimethyl-1.4-dihydropyridin-3.5-dicarbons{\"a}ure-dialkylestern, I},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82430},
  year      = {1980},
  abstract  = {no abstract available},
  subject      = {Chemie},
  language  = {de}
}