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  • 1
    ISSN: 1432-1041
    Keywords: Key words (Deaminohydroxy)toremifene ; Pharmacokinetics ; Triphenylethylene ; FC-1271a ; SERM
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Purpose: New selective estrogen-receptor modulators for the treatment and prevention of osteoporosis, cardiovascular disease and breast cancer are currently the focus of intense research. (Deaminohydroxy)toremifene (Z-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol; FC-1271a) has been shown to prevent bone resorption in rats while having no or weak estrogen-like effects on the uterus, which makes it a good candidate drug for osteoporosis prevention. Our purpose here was to examine the pharmacokinetics of (deaminohydroxy)toremifene in humans included in two phase-I studies. Methods: The first was a single-dose, dose-escalation study with 28 healthy male volunteers. Doses ranged from 10 mg to 800 mg. The second study was conducted during a 12-week period with 40 healthy, post-menopausal women, who received repeated oral doses of 25–200 mg. Standard pharmacokinetic parameters were assessed. Results: In the single-dose study, time to reach peak concentration (tmax) ranged from 1.3 h to 4.0 h; peak concentration (Cmax) ranged from 15 ng/ml to 445 ng/ml; and the estimated terminal elimination half-life (mean ± SD; t1/2) was 24.8 ± 7.0 h. In the repeated-dose study, tmax ranged from 1.9 h to 2.6 h at 6 weeks and from 2.5 h to 2.9 h at 12 weeks. Cmax ranged from 295 ng/ml to 1043 ng/ml at 6 weeks and from 25 ng/ml to 1211 ng/ml at 12 weeks. The average t1/2 at all dose levels was 29.7 ± 1.5 h (overall mean ± SD). Strong linear correlations between the dose and Cmax and between the dose and the area under the curve were observed in both studies. Conclusion: Our results indicate that (deaminohydroxy)toremifene has pharmacokinetics suitable for single daily dosing. The prophylactic use of this agent in women susceptible to development of osteoporosis, cardiovascular disease and breast cancer could, therefore, be tested using a once-daily dosing schedule similar to those of other hormone-replacement therapy regimens.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1434-4475
    Keywords: Dihetero[2.2]orthometacyclophane ; Dynamic NMR spectroscopy ; Conformational analysis ; Ring interconversion of 9-membered ring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Die N,N′-Ditosyl-diaza[2.2]orthometacyclophane5a, b wurden aus N,N-Ditosylmetaphenylendiamin durch Umsetzung mit (Z)-1,4-Dichlorbuten bzw. 1,2-Bisbrommethylbenzol gewonnen. Tieftemperatur-NMR-Untersuchungen ergaben, daß5b als 1:1 Mischung einer Sessel- und einer Bootkonformation des gespanntenE,Z-Diazanonadienringes vorliegt. Bei Raumtemperatur ist die zugehörige Ringinversion schnell in der NMR-Zeitskala, die entsprechenden Protonen in beiden Konformeren, auch die aller CH2-Brückenprotonen, ergeben gemittelte Signale. Bei tiefen Temperaturen wird zunächst die Inversion der Methylenbrücken eingefroren (Signale für zweiexo- und zweiendo-CH2-Protonen werden erhalten, ΔG ≠ ca. 52 kJ mol−1). Bei weiterer Temperatursenkung können nach Einfrieren eines zweiten dynamischen Prozesses Sessel- und Bootkonformer anhand von getrennten Signalsätzen identifiziert werden (die freie Aktivierungsenthalpie für den zugehörigen Sessel-Boot-Flip beträgt ΔG ≠ ca. 43.5 kJ mol−1). Die Zuordnung der1H- und13C-NMR-Resonanzen wurde mit Hilfe von zweidimensionalen NMR-Experimenten gesichert.
    Notes: Summary The N,N′-ditosyl-diaza[2.2]orthometacyclophanes5a, b were synthesized from N,N-ditosyl-metaphenylenediamine by reaction with (Z)-1,4-dichlorobutene and 1,2-bis-bromomethylbenzene, respectively. Low temperature NMR studies showed that the compound5b exists as a 1:1 mixture of chair and boat form of the strained (E,Z)-diazanonadiene ring. At room temperature all corresponding resonances are averaged on the NMR time scale (including all four ethylene bridge protons). Going to lower temperatures, in a first step the methylene bridge inversion is frozen (giving twoexo H and twoendo H, ΔG ≠ ca. 52kJmol−1). In a second step the chair and boat form can be observed separately (ΔG ≠ ca. 43.5 kJ mol−1 for the chair/boat flip). The assignments were confirmed by 2D NMR experiments.
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  • 3
    ISSN: 1434-4475
    Keywords: Thiocarbonic acid imide ; Thiocarbamic acid S-methylester ; Methylthiopropenoic acid amides ; Imides ; Rutaceae-Aurantioideae ; Glycosmis mauritiana ; Glycosmis parviflora
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Zusammenfassung Aus den lipophilen Blatt-Extrakten vonGlycosmis mauritiana undG. parviflora (Rutaceae-Aurantioideae) wurde mit MPLC und DC das neue Methylthiocarbonsäureimid Ritigalin als Hauptkomponente isoliert. Seine Struktur wurde mit spektroskopischen Methoden aufgeklärt (1H-,13C-NMR; MS, IR; UV).
    Notes: Summary From the lipophilic leaf extracts ofGlycosmis mauritiana andG. parviflora (Rutaceae-Aurantioideae), the novel thiocarbonic acid derived imide ritigalin was isolated as major component by MPLC and TLC. The structure was elucidated by spectroscopic evidence (1H,13C NMR; MS; IR; UV).
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Tetrahedron 48 (1992), S. 1209-1218 
    ISSN: 0040-4020
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0031-9422
    Keywords: Glycosmis cf. chlorosperma ; Rutaceae ; cinnamides ; imides. ; leaves ; methyl-thioamides
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0031-9422
    Keywords: G. pentaphylla ; Glycosmis mauritiana ; Rutaceae ; antifungal activity. ; chemosystematics ; cinnamides ; leaves ; methylthioamides
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0031-9422
    Keywords: Glycosmis angustifolia ; Rutaceae ; chemosystematics. ; leaves ; methylthiopropenoic acid amides ; sulphones
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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