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- Kirkland, Thomas A., et al.
(författare)
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Synthesis of glutamic acid analogs as potent inhibitors of leukotriene A(4) hydrolase
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 16:9, s. 4963-4983
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Tidskriftsartikel (refereegranskat)abstract
- Leukotriene B-4 (LTB4) is a potent pro-inflammatory mediator that has been implicated in the pathogenesis of multiple diseases, including psoriasis, inflammatory bowel disease, multiple sclerosis and asthma. As a method to decrease the level of LTB4 and possibly identify novel treatments, inhibitors of the LTB4 biosynthetic enzyme, leukotriene A(4) hydrolase (LTA(4)-h), have been explored. Here we describe the discovery of a potent inhibitor of LTA(4)-h, arylamide of glutamic acid 4f, starting from the corresponding glycinamide 2. Analogs of 4f are then described, focusing on compounds that are both active and stable in whole blood. This effort culminated in the identification of amino alcohol 12a and amino ester 6b which meet these criteria.
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| 3. |
- Leloudas, G., et al.
(författare)
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The normal Type Ia SN 2003hv out to very late phases
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 505:1, s. 265-279
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We study a thermonuclear supernova (SN), emphasizing very late phases. Methods: An extensive dataset for SN 2003hv that covers the flux evolution from maximum light to day +786 is presented. This includes 82 epochs of optical imaging, 24 epochs of near-infrared (NIR) imaging, and 10 epochs of optical spectroscopy. These data are combined with published nebular-phase IR spectra, and the observations are compared to model light curves and synthetic nebular spectra. Results: SN 2003hv is a normal Type Ia supernova (SN Ia) with photometric and spectroscopic properties consistent with its rarely observed B-band decline-rate parameter, Δ m15(B) = 1.61 ± 0.02. The blueshift of the most isolated [Fe ii] lines in the nebular-phase optical spectrum appears consistent with those observed in the IR at similar epochs. At late times there is a prevalent color evolution from the optical toward the NIR bands. We present the latest-ever detection of a SN Ia in the NIR in Hubble Space Telescope images. The study of the ultraviolet/optical/infrared (UVOIR) light curve reveals that a substantial fraction of the flux is “missing” at late times. Between 300 and 700 days past maximum brightness, the UVOIR light curve declines linearly following the decay of radioactive 56Co, assuming full and instantaneous positron trapping. At 700 days we detect a possible slowdown of the decline in optical-bands, mainly in the V-band. Conclusions: The data are incompatible with a dramatic infrared catastrophe (IRC). However, the idea that an IRC occurred in the densest regions before 350 days can explain the missing flux from the UVOIR wavelengths and the flat-topped profiles in the NIR. We argue that such a scenario is possible if the ejecta are clumpy. The observations suggest that positrons are most likely trapped in the ejecta. Based on observations collected at the European Southern Observatory, Paranal, Chile (ESO Programmes 073.D-0294(AB), 074.D-0259(BC) and 075.D-0116(AB)), Cerro Tololo Inter-American Observatory, Lick Observatory, Las Campanas Observatory, Siding Spring Observatory, and the Hubble Space Telescope. Tables 3, 4, and Appendix A are only available in electronic form at http://www.aanda.org
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