@article{TackePikiesWiesenbergeretal.1994,
  author    = {Tacke, Reinhold and Pikies, J. and Wiesenberger, F. and Ernst, L. and Schomburg, D. and Waelbroeck, M. and Christophe, J. and Lambrecht, G. and Gross, J. and Mutschler, E.},
  title     = {Sila-biperiden und endo-Sila-biperiden: Synthesen, Kristallstrukturen und antimuscarinische Eigenschaften},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64303},
  year      = {1994},
  abstract  = {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.},
  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{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}
}