TY  - JOUR
A1  - Braunschweig, Holger
A1  - Dewhurst, Rian D.
A1  - Schwab, Katrin
A1  - Wagner, Katharina
T1  - {N ',N ''-Bis[2,6-bis(1-methylethyl)phenyl]-N,N-dimethylguanidinato-kappa N-2 ',N ''}dibromidoborane
N2  - In the molecular structure of the title compound, C27H40N3BBr2, the B atom is connected to two bromide substituents and a guanidinate scaffold, forming a four– membered ring. An aryl group is connected to each N atom in the ring that contains two isopropyl groups in positions 2 and 6.
KW  - Anorganische Chemie
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67622
ER  - 
TY  - JOUR
A1  - Braunschweig, Holger
A1  - Damme, Alexander
T1  - 1,2-Bis(dimethylamino)-1,2-bis(2,4,6-triisopropylphenyl)diborane(4)
N2  - In the molecular structure of the title compound, C34H58B2N2, each B atom of the diborane(4) is connected to one dimethylamino group and one Tip ligand (Tip = 2,4,6-triisopropylphenyl). These findings indicate that the increased steric demand of the Tip groups exerts influence solely on the B—B separation but not on the overall geometry of the title compound.
KW  - Anorganische Chemie
Y1  - 2010
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67639
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schnering, Hans Georg von
T1  - Ab Initio Comparision of the (MX\(_2\))\(_2\) Dimers (m=Zn, Cd, Hg; X F, Cl, H), and Study of Relativistic Effects in Crystalline HgF\(_2\)
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59971
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schnering, Hans Georg von
T1  - Origin of the Unique Stability of Condensed-Phase Hg\(_2 ^{2+}\). An ab Initio Investigation of M\(^I\) and M\(^{II}\) Species (M= Zn, Cd, Hg)
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59981
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schnering, Hans Georg von
T1  - The Dominance of Linear 2-Coordination in Mercury Chemistry: Quasirelativistic and Nonrelativistic ab Initio Pseudopotential Study of (HgX\(_2\))\(_2\) (X=F, Cl, Br, I, H)
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59995
ER  - 
TY  - JOUR
A1  - Wissing, Elmo
A1  - Kaupp, Martin
A1  - Boersma, Jaap
A1  - Spek, Anthony L.
A1  - Koten, Gerard van
T1  - Alkylation Reactions of Dialkylzinc Compounds with 1,4- Diaza- 1,3-butadienes: Cationic and radical Anionic Organozinc Intermediates. Molecular Structure of the Cationic Organozinc Species [MeZn(t-BuN=CHCH=N-t-Bu)]O\(_3\)SCF\(_3\) and Me\(_2\)Zn(bpy)(bpy = 2,2' -Bipyridine)
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60008
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Dolg, Michael
A1  - Stoll, Hermann
A1  - Schnering, Hans Georg von
T1  - Oxidation State +IV in Group 12 Chemistry : Ab Initio Study of Zinc(IV), Cadmium(IV), and Mercury(IV) Fluorides
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60018
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  - Sperlich, J.
A1  - Becker, B.
T1  - Bis[2,3-naphthalenediolato(2-)](pyrrolidinio-methyl)germanate-tetartoacetonitrile, the first zwitterionic \(\lambda_5\)-germanate: synthesis and crystal structure analysis
N2  - The zwitterionic spirocyclic \(\lambda_5\)-germanate bis(2,3-naphthalenediolato( 2-)](pyrrolidiniomethyl)germanate (8) was synthesized and the crystal structure of its tetartoacetonitrile solvate 8 · 1/4 CH\(_3\)CN studied by single-crystal X-ray diffraction. Compound 8 was prepared by reaction of (MeO)\(_3\)GeCH\(_2\)NC\(_4\)H\(_8\) (11; NC\(_4\)H\(_8\) = pyrrolidino) with two equivalents of 2,3-naphthalenediol (isolated as 8 · 1/4 CH\(_3\)CN; yield 92%). The coordination polyhedron around the pentacoordi- naphthalenediolatonate germanium atom of 8 · 1/4 CH\(_3\)CN can be described as a strongly distorted trigonal bipyramid (the structure is displaced by 38.9% from the ideal trigonal bipyrarnid towards the ideal square pyramid), the carbon atom occupying an equatorial position. In the crystal lattice of 8 · 1/4 CH\(_3\)CN, the zwitterions form intermolecular N-H ... o hydrogen bonds leading to the formation of dimers. 1H- and \(^{13}\C-NMR studies revealed that 8 also exists in solution ([D\(_6\)]DMSO).
KW  - Anorganische Chemie
KW  - Lambda5-Germanate
KW  - zwitterionic
KW  - Germanium
KW  - pentacoordinate
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64329
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Lopez-Mras, A.
A1  - Jones, P. G.
T1  - Syntheses, crystal structure analyses, and NMR studies of [2-(dimethylammonio)phenyl]bis[glycolato(2-)-O1,O2]silicate and related zwitterionic spirocyclic \(\lambda_5\)Si-silicates
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64339
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  - 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  - Wagner, S. A.
A1  - Brakmann, S.
A1  - Wuttke, F.
A1  - Eilert, U.
A1  - Fischer, L.
A1  - Syldatk, C.
T1  - Synthesis of acetyldimethyl(phenyl)silane and its enantioselective conversion into (R)-(1-hydroxyethyl)dimethyl(phenyl)silane by plant cell suspension culytures of Symphytum officinale L. and Ruta graveolens L.
N2  - Starting from chlorodimethyl(phenyl)silane (3), acetyldimethyl(phenyl)silane (l) was prepared by a two-step synthesis in a total yield of 90% [PhMe\(_2\)SiCl (3)-> PhMe\(_2\)SiCCOMe)=CH\(_2\) (4)-> PhMe\(_2\)SiC(O)Me (1)]. The prochiral acetylsilane 1 was transfonned enantioselectively into (R)-(1-hydroxyethyl)dimethyl(phenyl)silane [(R)-2] using plant cell Suspension cultures of Symphytum officinale L. or Ruta graveolens L. Under preparative conditions (300-mg scale, not optimized), (R)-2 was isolated in 15% (Symphytum) and 9% yield (Ruta), respectively. The enantiomeric purities of the products were 81% ee (Syrnphytum) and 60% ee (Ruta), respectively.
KW  - Anorganische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64299
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schnering, Hans Georg von
T1  - Gaseous Mercury(IV) Fluoride, HgF\(_4\): An ab Initio Study
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60038
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
T1  - The Peculiar Coordination of Brium: Ab Initio Study of the Molecular and Electronic Structures of the Group 2 Dihydride Dimers M\(_2\)H\(_4\) (M=Mg, Ca, Sr, Ba)
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60048
ER  - 
TY  - JOUR
A1  - Lambert, Christoph
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
T1  - “Inverted” Sodium-Lithium Electronegativity: Polarity and Metalation Energies of Organic and Inorganic Alkali-Metal Compounds
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60054
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
T1  - Ab Initio Study of Structures and Stabilities of Substituted Lead Compounds. Why is Inorganic Lead Chemistry Dominated by Pb\(^{II}\) but Organolead Chemistry by Pb\(^{IV}\)?
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60069
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Becht, J.
A1  - Lopez-Mras, A.
A1  - Sheldrick, W. S.
A1  - Sebald, A.
T1  - Syntheses, X-ray crystal structure analyses, and solid-state NMR studies of some zwitterionic organofluorosilicates
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64272
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  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
A1  - Stoll, Hermann
T1  - Model CaH\(_2\)(L) and CaF\(_2\)(L) Complexes (L = Ne, Ar, Kr, Xe, CO, N\(_2\)): Consequences of Interactions between "Inert-Gas" Ligands and Floppy Molecules
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60078
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Charkin, Oleg P.
A1  - Schleyer, Paul von Rague
T1  - The Ions MCp\(^{2+}\) (M = Sc, La): Significantly Bent Sandwich Species
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60082
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
A1  - Dolg, Michael
A1  - Stoll, Hermann
T1  - The Equilibrium Structures of Monomeric Group 2 and Lanthanide(II) Metallocenes MCp2 (M = Ca, Sr, Ba, Sm, Eu, Yb) Studied by ab Initio Calculations
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60139
ER  - 
TY  - JOUR
A1  - Schleyer, Paul von Rague
A1  - Kaupp, Martin
A1  - Hampel, Frank
A1  - Bremer, Matthias
A1  - Mislow, Kurt
T1  - Relationships in the Rotational Barriers of Group 14 Ethane Congeners H\(_3\)X-YH\(_3\) (X, Y = C, Si, Ge, Sn, Pb). Comparisons of ab Initio Pseudopotential and All-Electron Results
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60147
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Becker, B.
A1  - Berg, D.
A1  - Brandes, W.
A1  - Dutzmann, S.
A1  - Schaller, S.
T1  - Bis(4-fluorophenyl)methyl(1H-1,2,4-triazol-1-yl-methyl)germane, a germanium analogue of the agricultural fungicide flusilazole: synthesis and biological properties
N2  - Bis( 4-fluorophenyl)methyl(l H-1,2,4-triazol-1-yl-methyl)germane (2), a germanium analogue of the agricultural fungicide flusilazole (1), has been synthesized from Cl\(_3\)GeCH\(_2\)CI (3) by both a three-step and a four-step synthesis (3-> (p-F-C\(_6\)H\(_4\))\(_2\)Ge(CH\(_2\)Cl)Br (4)-> (p-F-C\(_6\)H\(_4\))\(_2\)Ge(CH\(_2\)CI)CH\(_3\) (S)-> 2; S ~ (p-F-C\(_6\)H\(_4\))\(_2\)Ge(CH\(_2\)I)CH\(_3\) (6)-> l). The fungicidal properties of l have been compared with those of the parent silicon compound 1 (studies on Si/Ge bioisosterism). In various test systems, the SijGe analogues 1 and 2 showed comparable fungicidal properlies (in activity against plant pathogenic fungi: in agar plate diffusion tests and greenhause evaluations; in activity against human pathogenic fungi: in serial dilution tests). In addition, 1 and 2 displayed comparable potencies in respect of sterol biosynthesis inhibition in Sacclulromycopsis üpolytica and Pyricularia oryzae, the mode of action being primarily an inhtbition of oxidative C14-demethylation.
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64224
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  - Bungardt, E.
A1  - Vockert, E.
A1  - Feifel, R.
A1  - Moser, U.
A1  - Tacke, Reinhold
A1  - Mutschler, E.
A1  - Lambrecht, G.
A1  - Suprenant, A.
T1  - Characterization of muscarinic receptors mediating vasodilation in guinea-pig ileum submucosal arterioles by the use of computer-assisted videomicroscopy
N2  - 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.
KW  - Anorganische Chemie
KW  - Muscarinic receptor subtypes; Muscarinic rcceptor agonists (M 1-selective)
KW  - Muscarinic receptor antagonists (M 3-selective)
KW  - Vidcomicroscopy
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64206
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
T1  - Struktur- und Stabilitätstrends bei Fluor(methyl)plumbanen
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60091
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
T1  - The Structure and Stability Trends Fluoro(methyl)plumbanes
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60105
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
T1  - Do Low-Coordinated Group 1-3 cations M\(^n\) \(^+\)L\(_m\) (Mn\(^+\) = K\(^+\), Rb\(^+\), Cs\(^+\), Ca\(^{2+}\), Sr\(^{2+}\), Ba\(^{2+}\), Sc\(^{3+}\), Y\(^{3+}\), La\(^{3+}\); L = NH\(_3\), H\(_2\)0, HF; m = 1-3) with a Formal Noble-Gas Electron Configuration Favor Regular or "Abnormal" Shapes?
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60111
ER  - 
TY  - JOUR
A1  - Mösges, Gabriele
A1  - Hampel, Frank
A1  - Kaupp, Martin
A1  - Schleyer, Paul von Rague
T1  - Experimental and Theoretical studies of Alkaline earth and Alkali Metal Coordination: X-ray crystal structures of Calcium, Strontium, and Barium Carbazoles and ab Initio Model calculations
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60127
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul. von Rague
T1  - The Structural Variations of Monomeric Alkaline Earth MX\(_2\)-Compounds (M = Ca, Sr, Ba; X = Li, BeH, BH\(_2\), CH\(_3\), NH\(_2\),OH, F). An ab Initio Pseudopotential Study
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60152
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Wuttke, F.
A1  - Henke, H.
T1  - Zur Stereochemie der mikrobiellen Reduktion von rac-Acetyl( t-butyl)methylphenylsilan mit Trigonopsis variabilis (DSM 70714) und Corynebacterium dioxydans (ATCC 21766): Aufklärung der absoluten Konfiguration der Biotransformationsprodukte (SiR,CR)- und ( SiS ,CR)-t-Butyl( 1-hydroxyethyl)methylphenylsilan
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64176
ER  - 
TY  - JOUR
A1  - Feifel, R.
A1  - Rodrigues de Miranda, J. F.
A1  - Strohmann, C.
A1  - Tacke, Reinhold
A1  - Aasen, A. J.
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Selective labelling of muscarinic M\(_1\) receptors in calf superior cervical ganglia by [\(^3\)H](\(\pm\))-telenzepine
N2  - A method was developed to detennine the affinities of antimuscarinic drugs at M\(_1\) receptors. [\(^3\)H](±)-Telenzepine served as radioligand in crude preparations of calf superior cervical ganglia and showed high affinity for a single receptor population. consisting of M1 receptors (K\(_D\) = 1.12 nM). Kinetic experiments showed monophasic association (k\(_1\) =0.017 min\(^{-1}\) nM\(^{-1}\) ) and dissociation (k\(_1\) = 0.017 min\(^{-1}\) ) kinetics, the half-life of dissociation being 41 min at 37°C. The kinetie K\(_D\) value amounted to 1.00 nM. M\(_1\) affinities for pirenzepine, methoctramine. hexahydro-sila-difenidol and p-fluoro-hexahydro-sila-difenidol detennined in competition experiments were similar to those found in functional studies with MI receptors in rabbit isolated vas deferens. The binding assay was used to deterriline the affinities of the (R) and (S) enantiomers of tertiary (trihexyphenidyl, hexahydro-difenidol. hexbutinol, p-fluoro-hexbutinol) and quatemary musearlnie antagonists (trihexyphenidyl methiodide. hexbutinol methiodide). Comparison of results obtained with the rabbit vas deferens suggested that the ionic environment may influence the affinities.
KW  - Anorganische Chemie
KW  - Muscarinic M1 receptors
KW  - Superior cervical ganglia (calf)
KW  - Hexahydro-difenidol analogues
KW  - Trihexyphenidyl
KW  - Hexbutinol
KW  - Stereoselectivity
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64082
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Brakmann, S.
A1  - Wuttke, F.
A1  - Fooladi, J.
A1  - Syldatk, C.
A1  - Schomburg, D.
T1  - Stereoselective microbial reduction of racemic acetyl(t-butyl)methylphenylsilane by Trigonopsis variabilis (DSM 70714) and Corynebacterium dioxydans (ATCC 21766)
N2  - (SiR,CR)- and (SiS,CR)-t-butyl(l-hydroxyethyl)methylphenylsilane [(SiR,CR)-2 and (SiS,CR)-3] have been prepared by (R)-selective microbial rcduction of racemic acetyl(t-butyl)methylphenylsilane (rac-1) using resting free cells of the yeast Trigonopsis variabilis (DSM 70714) or the bacterium Corynebacterium dioxydans (ATCC 21766). The biotransfonnations were carried out on a 10 g scale. Afterseparation by column chromatography on silica gel, the optically active diastereomers (SiR,CR)-2 and (SiS,CR)-3 produccd by T. variabilis were obtained in good yields [74% ((SiR,CR)-2). 78% ((SiS,CR)-3)]. The products obtained from the reduction with C. dioxydans were isolated in significantly lower yields [20% ((SiR,CR)-2), 20% ((SiS,CR)-3)]; reaction conditions not optimized). Both bioconversions gave products with high enantiomeric purities (T. variabilis: 91% ee ((SiR,CR)-2), 96% ee ((SiS,CR)-3); C. dioxydons: ~ 991 ee ((SiR,CR)-l), ~ 99% ee ((SiS,CR)-3)). To throw light on the stereochemical aspects of these biotransfonnations, an X-ray diffraction study was carried out on the 3,5-dinitrobenzoate of rac-(SiR,CS/SiS,CR)-3. In addition, 1H NMR spectroscopic stereochemical correlation studies were performed with the (S)-MTPA esters derived from (SiR,CR)-l, (SiS,CR)-3, rac-(SiR,CRjSiS,CS)-2 and rac-(SiR,CSjSiS,CR)-3 [rac-(SiR,CR/ SiS,CS)-2 and rac-(SiR,CS/SiS,CR)-3 were obtained by reduction of rac-1 with LiAIH\(_4\) in diethylether, followed by chromatographic separation of the diastereomers on silica gel]. These stereochemical studies allowed assignment of the absolute configurations and enantiomeric purities of the biotransformation products.
KW  - Anorganische Chemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64109
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Schleyer, Paul. von Rague
A1  - Stoll, Hermann
A1  - Preuss, Heinzwerner
T1  - The Question of bending of the Alkaline Earth Dihalides MX\(_2\) (M = Be, Mg, Ca, Sr, Ba; X = F, C1, Br, I). An ab Initio Pseudopotential Study
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60166
ER  - 
TY  - JOUR
A1  - Kaupp, Martin
A1  - Stoll, Hermann
A1  - Preuss, Heinzwerner
A1  - Kaim, Wolfgang
A1  - Stahl, Thomas
A1  - van Koten, Gerard
A1  - Wissing, Elmo
A1  - Smeets, Wilberth J. J.
A1  - Spek, Anthony L.
T1  - Theoretical and Experimential Study of Diamagnetic and Paramagnetic Products from Thermal and Light-Induced Alkyl Transfer between Zinc or Magnesium Dialkyls and 1,4-Diaza-1,3-butadiene Substrates
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60173
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  - 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  - Strohmann, C.
A1  - Bauerecker, S.
A1  - Cammenga, H. K.
A1  - Jones, P. G.
A1  - Mutschler, E.
A1  - Lambrecht, G.
A1  - Tacke, Reinhold
T1  - Enantiomers of the muscarinic antagonist 1-cyclohexyl-1-(4-fluorophenyl)-4-piperidino-1-butanol (p-fluoro-hexahydro-difenidol): synthesis, absolute configuration, and enantiomeric purity
N2  - The enantiomers of the antimuscarinic agent 1-cyclohexyl-1- (4-fluorophenyl)-4-piperidino-1-butanol [(R)- and (S)-p-fluorohexahydro- difenidol] ((R)- and (S)-2a] and their methiodides (R)- 3 and (S)-3 were prepared with high enantiomeric purity. (R)- 2a and (S)-2a (isolated as hydrochlorides) were obtained by catalytic hydrogenation (Pd/C contact) of the corresponding enantiomers of 1-cyclohexyl-1-( 4-fl uorophen yl)-4-piperidino- 2-butyn-1-ol [(R)- and (S)-4]. Reaction of (R)-2a and (S)-2a with rnethyl iodide led to (R)-3 and (S)-3, respectively. The unsaturated precursors (R)- and (S}-4 (enantiorneric purity ~ 99.80 and ~99.94% e.e.; calorimetric analysis) were prepared by res-sepaolution of rac-4 [available from 4-FC\(_6\)H\(_4\)C(O)C\(_6\)H\(_{11}\) by reaction with LiC ~ CCH\(_2\)NC\(_5\)H\(_{10}\)] using (R)- and (S)-mandelic acid as resolving agents. The absolute configurations of the (R) and (S) enantiomers of 2a, 3, and 4 were determined by an X-ray crystal-structure analysis of (S)-5, the methiodide of (S)-4. (R)- 2a and (R)-3 exhibit a higher affinity for muscarinic M1, M2, M3, and M4 receptors (by up to two orders of magnitude) than their corresponding antipodes (S)-2a and (S)-3, the degree of stereoselectivity depending on the receptor subtype involved. (R)-2a represents a useful tool for rnuscarinic receptor research (affinity profile: M1 ~ M3 ~ M4 > M2).
KW  - Anorganische Chemie
KW  - Difenidol
KW  - p-fluoro-hexahydro-
KW  - enantiomers of / Muscarinic receptors
KW  - subtypes of
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64144
ER  - 
TY  - JOUR
A1  - Hengelsberg, H.
A1  - Tacke, Reinhold
A1  - Fritsche, K.
A1  - Syldatk, C.
A1  - Wagner, F.
T1  - Synthesis and enantioselective enzymatic hydrolysis of rac-dimethylphenyl[1-(phenylacetamido)- ethyl]silane
N2  - Racemic dimethylphenyl(l-(phenylacetamido)ethyl)silane [rac-5) has been made by a four-step synthesis starting from (chloromethyl)dimethylphenylsilane [PhMe\(_2\)SiCH2Cl (1) ~ PhMe\(_2\)SiCH(Cl)Me (rac-2) - PhMe\(_2\)SiCH(l)Me (rac-3) - PhMe2SiCH(NH2)Me (rac-4) ~ PhMe\(_2\)SiCH[N(H)C(O)CH\(_2\)Ph]Me ( rac-5); total yield 41% ). Enantioselective enzymatic hydrolysis of rac-5, catalyzed by immobilized penicillin G acylase (E.C. 3.5.1.11) from Escherichia coli 5K (pHM 12), gave (R)-(1- aminoethyl)dimethylphenylsilane [( R )-4] in 40% yield with an enantiomeric purity of 92% ee.
KW  - Anorganische Chemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64153
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Mahner, K.
A1  - Strohmann, C.
A1  - Forth, B.
A1  - Mutschler, E.
A1  - Friebe, T.
A1  - Lambrecht, G.
T1  - Cyclohexyl(4-fluorophenyl)(3-piperidinopropyl)silanol (p-fluoro-hexahydro-sila-difenidol, p-F-HHSiD) and derivatives: synthesis and antimuscarinic properties
N2  - Four different syntheses of the potent and selective muscanruc antagonist cyclohexyl( 4- fluorophenyl)(3-piperidinopropyl)silanol ( p-fluoro-hexahydro-sila-difenidol, p-F-HHSiD (2b); isolated as hydrochloride 2b· HCl) are described (starting materials: (CH\(_3\)O)\(_2\)SiCH\(_2\)CH\(_2\)CH\(_2\)Cl and Si(OCH\(_3\))\(_4\) ). In addition, the synthesis of the corresponding carbon analogue p-fluoro-hexahydro-difenidol ( p-F-HHD (2a); isolated as 2a· HCI) and the syntheses of three p-F-HHSiD derivatives (3-5), with a modified cyclic amino group, are reported (3: piperidinojpyrrolidino exchange, isolated as 3· HCI; 4: piperidinoj hexamethylenimino exchange, isolated as 4 · HCl; 5: quaternization of 2b with methyl iodide). The chiral compounds 2a, 2b, 3, 4 and 5 were prepared as racemates. In functional pharmacological studies, 3-5 behaved as simple competitive antagonists at musearlnie Ml receptors in rabbit vas deferens, M2 receptors in guinea-pig atria, and M3 receptors in guinea-pig ileal smooth rnuscle. The pyrrolidino (3) and hexamethylenimino (4) analogues of the parent drug p-F-HHSiD (2b) displayed the highest affinity for Ml and M3 receptors (pA\(_2\) values: 7.0-7.4) but exhibited lower affinity for cardiac M2 receptors (pA\(_2\) : 5.9 and 6.0). Their affinity profile (Ml- M3 > M2) is different from that of p-F-HHSiD (2b) (M3 > Ml > M2), but qualitatively very similar tothat of p-F-HHD (2a). The methiodide 5 exhibited the highest affinity for Ml receptors (pA\(_2\) : 8.5) but lower affinity for M2 and M3 receptors by factors of 5.6 and 3.6, respectively.
KW  - Anorganische Chemie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64162
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  - 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  - Friebe, T.
A1  - Tacke, Reinhold
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Novel pharmacological profile of muscarinic receptors mediating contraction of the guinea-pig uterus
N2  - The present study was designed to further characterize the muscarinic receptors mediating contraction of the guinea-pig uterus. The affinities of various selective muscarinic antagonists were determined and compared with those obtained at M\(_1\) (rabbit vas deferens), M\(_2\) (guinea-pig atria) and M\(_3\) receptors (guinea-pig ileum). The contractile responses of uterine smooth muscle from immature guinea-pigs to carbachol (pD\(_2\) = 5.73) were competitively antagonized by pirenzepine (pA\(_2\) = 7.04), AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]- 5,11-dihydro-6H -pyrido[2,3-b][1 ,4]benzo. diazepin-6-one) (pA\(_2\) = 6.96), himbacine (pA\(_2\) = 7.92), methoctramine (pA\(_2\) = 7.52), 4-DAMP (4-diphenylacetoxy- N-methylpiperidine methiodide) (pA\(_2\) = 8.87) and sila-hexocyclium (pA\(_2\) = 8.81). A comparison of affinity values indicates that the muscarinic receptors present in guinea-pig uterus display a novel pharmacological profile which is not consistent with the presence of either an M\(_1\), M\(_2\) or M\(_3\) receptor. The affinities determined for the different antagonists rather showed a close similarity to those obtained at muscarinic receptors present in rat striatum and NG108-15 cells which are considered pharmacological equivalents (M\(_4\) receptors) of the m4 gene product. We thus hypothesize that the guinea-pig isolated uterus preparation may serve as a simple functional assay system to study the pharmacology of M\(_4\) receptors.
KW  - Anorganische Chemie
KW  - Muscarinic receptors
KW  - M4 receptors
KW  - Guinea-pig uterus
KW  - Pirenzepine
KW  - Methoctramine
KW  - Sila-hexocyclium
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64071
ER  - 
TY  - JOUR
A1  - Verspohl, E. J.
A1  - Tacke, Reinhold
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Muscarinic receptor subtypes in rat pancreatic islets: binding and functional studies
N2  - Cholinergie agents arepotent modulators of insulin release that aet via musearinie reeeptors. We now investigated the muscarinic receptor subtype present in rat panereatic islets in binding and funetional studies. Binding of 5 nM [ \(^3\)H]N-methylscopolamine ([\(^3\)H]NMS) was half maximal at 30 min. At 60 min, the maximal total bindingwas 1.29% and the non-specifie binding (presence of 100 ,uM atropine) was 0.18% of the total radioaetivity per 10 f.'g islet protein. Unlabelled atropine inhibited [\(^3\)H]NMS binding with an IC50 of ca. 30 nM. The rank order of antagonist high-affinity binding was atropine > sila-hexocyelium methyl sulfate (SiHC; M\(_1\) > M\(_3\) > M\(_2\) ) > pirenzepine (M\(_1\)> M\(_2\) = M\(_3\) ) = methoctramine (M\(_2\) > M\(_1\) > M\(_3\) ). The high-affinity K\(_d\)s were 8.5, 56, 1300 and 1300 nM, respectively. The high affinity Kd of the muscarinie receptor agonist, arecaidine propargyl ester (APE), was 8.1 nM. The EC\(_{50}\) for the biologieal effects of APE on insulin and glucagon secretion was 3.2 and 2.3 nM. The rank order for the high-affinity biological effects of antagonists (inhibition of APE-mediated insulin/ glucagon release) was almost the same as for binding. The data indicate that rat pancreatie islets contain neither an M\(_1\) subtype (high-affinity for pirenzepine) nor an M\(_2\) subtype (high-affinity for methoctramine) receptor. However, the data evidence an M\(_3\) receptor subtype, since SiHC in the absence of the M\(_1\) receptor subtype shows a relatively high affinity to the receptors in rat panereatic islets.
KW  - Anorganische Chemie
KW  - Muscarinic receptor subtypes
KW  - Islets of Langerhans (rat)
KW  - Insulin
KW  - Glucagon
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63993
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  - 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  -