192803-60-4Relevant articles and documents
Simple syntheses of (S)-2- and 4-amino-5-hydroxypentanoic acids
Barlos,Mamos,Papioannou,Patrianakou
, p. 1583 - 1584 (1987)
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Antiviral and tumor cell antiproliferative SAR studies on tetracyclic eudistomins-II
Van Maarseveen, Jan H.,Scheeren, Hans W.,De Clercq, Erik,Balzarini, Jan,Kruse, Chris G.
, p. 955 - 970 (2007/10/03)
In a search for the minimum pharmacophore of the naturally occurring tetracyclic eudistomins, five structural analogues (4-8) were evaluated for their in vitro antiviral and tumor cell antiproliferative activities. For the synthesis of these derivatives both intra- and intermolecular Pictet-Spengler reactions have been used. Opening of the P-carboline annulated 7-membered D-ring in 6 and 7 resulted in a complete loss of activity. On the other hand, replacement of either the oxygen atom or the sulfur atom in the 7-membered ring by a methylene group in 5 and 8, respectively, is allowed. These results combined with previous SAR data underline the crucial importance of the D-ring in eudistomins as a scaffold for the correct positioning of both basic nitrogen atoms. Also bioisosteric replacement of the bicyclic indole system with a dimethoxyphenyl group, to give the isoquinoline skeleton, is allowed. The tricyclic isoquinoline derivative 4 is, so far, the most promising antiviral analogue; it combines a high potency (MIG at 100 ng/ mL (340 nM)) with high MCC/MIC ratios (ranging from 1000 to 5000 against HSV-1, HSV-2, vaccinia virus, and vesicular stomatitis virus).
