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Strom T Shokati T Klawitter J Klawitter J Hoffman K Schiebel HM Christians U 《Journal of mass spectrometry : JMS》2011,46(7):615-624
SAR-943 (32-deoxo rapamycin) is a proliferation signal inhibitor via interaction with the mammalian target of rapamycin (mTOR). Most importantly, SAR-943 has improved chemical stability compared to rapamycin (sirolimus) and is currently under investigation as a drug coated on coronary stents. It was the goal of this study to identify the SAR-943 metabolites generated after incubation with human liver microsomes using high-resolution mass spectrometry (MS) and MS/iontrap (MS(n)) and comparison of fragmentation patterns of the metabolites with those of SAR-943 and other known rapamycin derivatives. Our study showed that SAR-943 is mainly hydroxylated and/or demethylated by human liver microsomes. The structures of the following metabolites were identified: O-demethylated metabolites: 39-O-desmethyl, 16-O-desmethyl and 27-O-desmethyl SAR-943; hydroxylated metabolites: hydroxy piperidine SAR-943, 11-hydroxy, 12-hydroxy, 14-hydroxy, 23-hydroxy, 24-hydroxy, 25-hydroxy, 46-hydroxy and 49-hydroxy SAR-943; didemethylated metabolites: 16,39-O-didesmethyl and 27,39-O-didesmethyl SAR-943; demethylated-hydroxylated metabolites: 39-O-desmethyl, 23- or 24-hydroxy and 39-O-desmethyl, hydroxy piperidine SAR-943 and dihydroxylated metabolites: 12-,23- or 24-dihydroxy SAR-943. In addition, several other demethylated-hydroxylated and dihydroxylated metabolites were detected. However, their exact structures could not be identified. 相似文献
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Background
Numerous stroke studies have controversially shown estrogens to be either neuroprotective or neurodamaging. The discordant results observed in rat brain ischemia models may be a consequence of discrepancies in estrogen administration modes resulting in plasma concentration profiles far from those intended. To test this hypothesis we reproduced in detail and extended an earlier study from our lab using a different mode of 17β-estradiol administration; home-made silastic capsules instead of commercial slow-release 17β-estradiol pellets. Four groups of female rats (n = 12) were ovariectomized and administered 17β-estradiol or placebo via silastic capsules. All animals underwent MCAo fourteen days after ovariectomy and were sacrificed three days later. 相似文献4.
The Jahn-Teller (J-T) effect in systems of four-fold symmetry is well known to differ from that in all other point groups with respect to the nature of the J-T active normal modes of vibration. The present report addresses some previously unnoticed features which are of intrinsic importance in recognizing and understanding the unique manifestations of quadrate symmetry in both the static and dynamic Jahn-Teller effects. We first consider the nature of the static J-T potential surfaces when coupling to and strains in two modes, b 1 and b 2, are included in the hamiltonian. The second part of this paper is devoted to an examination of the dynamic J-T effect in four-fold systems. Utilizing both perturbation theory and numerical solution to the Schrödinger equation, we examine the spin-hamiltonian parameters for a metalloporphyrin 3 Eu triplet state and discuss some dynamical processes, including reorientation of the system between minima, spin-lattice relaxation, and the dependences of these phenomena on the nature and magnitude of the off-diagonal terms in the hamiltonian. There emerge from this analysis several signal differences between the Jahn-Teller effect for a doubly degenerate state in four-fold systems and in the more usual cubic or tetrahedral situation. 相似文献
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M. Werner P. Brenner N. Goldowski R. Heinze M. Marder H. von der Heyden D. A. Strom B. M. Rybak M. M. Ognew A. Cousen G. Schikorr Z. Karpinski Ch. Dufraisse R. May K. Laurell und M. G. Ammon 《Fresenius' Journal of Analytical Chemistry》1938,115(7-8):283-289
Ohne Zusammenfassung 相似文献
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Numerical Algorithms - The problem of computing the roots of a particular sequence of sparse polynomials pn(t) is considered. Each instance pn(t) incorporates only the n +?1 monomial terms... 相似文献