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- Adrian Meredith, Jenny, 1971-, et al.
(författare)
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Design and Synthesis of BACE-1 Inhibitors Containing a New Hydroxyethylene (HE) Scaffold: Potent activities in a cellular assay
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In a preceding report from our group we disclosed the development of a novel HE transition state isostere with a difluorophenoxymethyl side chain in the P1 position and a methoxy group in the P1’ position furnishing highly potent inhibitors of BACE-1 (i.e. lead compound 1), which moreover exhibit very promising selectivity over cathepsin D. In a continuation of this work with the aim at improving on the cell-based activity and pharmacokinetic properties, we have further developed the SAR for the P1 side chain of inhibitor 1 whereby the P1 side chain oxygen has been substituted for an amine, a carbon or a bond. The chemistry developed for the previous HE inhibitor structure 1 has now been extended to readily accommodate the introduction of new P1 side chains into this new HE scaffold. These modifications have given rise to several highly potent inhibitors where the most potent displayed a BACE-1 Ki value of 0.2 nM and a cell-based Aβ40 IC50 value of 9 nM. Thus, regarding the enzyme inhibition in the cell assay a more than 600-fold improvement compared to compound 1 was achieved via minor structural alterations.
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- Peeker, Ralph, 1958
(författare)
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Ureteric reconstruction and replacement.
- 2009
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Ingår i: Current opinion in urology. - 1473-6586.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: To review the recent advances on ureteric reconstruction and replacement, in particular, ileal ureteric replacement and laparoscopic and robotic-assisted ureteral reconstruction. RECENT FINDINGS: Recently, the ureteric replacement with bowel has been carefully assessed by several authors, and the results are quite impressive. Also, very recent studies on laparoscopic and robotic-assisted ureteral repair have been published. Outcomes appear very promising, allowing for a faster recovery and shorter hospital stay for the patient. SUMMARY: Today, we can conclude that the field of ureteric reconstruction and replacement is still evolving. Old techniques are supported by an increasing degree of evidence, and new, more minimally invasive surgical strategies emerge. Clearly, there are some disadvantages as well as difficulties to overcome with the new techniques; however, recent studies appear to present promising results.
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- Persson, Ingmar, 1951
(författare)
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Välvillig egalitarianism
- 2005
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Ingår i: Tidskrift för politisk filosofi. - 1402-2710. ; :1, s. 47-49
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Tidskriftsartikel (refereegranskat)
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