Approaches for introducing high molecular diversity in scaffolds: Fast parallel synthesis of highly substituted 1H-quinolin-4-one libraries |
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Authors: | Kuznetsov Vladimir Gorohovsky Sofia Levy Amalia Meir Simcha Shkoulev Vladimir Menashe Naim Greenwald Moshe Aizikovich Alexander Ofer Dror Byk Gerardo Gellerman Garry |
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Affiliation: | Compugen Ltd, Ashkelon 78785, Israel. |
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Abstract: | We have developed a two steps strategy for the parallel synthesis of highly diversified quinolin-ones. In the first step we have combined and improved different synthetic methods for generating quinolin-4-ones bearing four different substitutions at specific positions using round bottomed flasks. The synthesis was assessed for a large number of substituted quinolin-4-ones. In the second step, the improved method was adapted to a parallel array synthesis using a 12 positions carrousel as demonstrated for the synthesis of 42-variable quinolin-4-ones. The first combinatorial library set 14(a-x) was obtained with a chemical purity of more than 95% without purification, the second library set 15(a-r), which included two synthetic steps, needed combinatorial purification using an innovative parallel purifier. The proposed approach contributes to a more extensive diversification of molecular scaffolds in general and provides access to highly substituted quinolinones in particular. |
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Keywords: | 1H-quinolin-one scaffold decoration |
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