Approaches for introducing high molecular diversity in scaffolds: fast parallel synthesis of highly substituted 1H-quinolin-4-one libraries.
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.
Kuznetsov
Vladimir
V
Compugen Ltd, Ashkelon 78785, Israel.
Gorohovsky
Sofia
S
Levy
Amalia
A
Meir
Simcha
S
Shkoulev
Vladimir
V
Menashe
Naim
N
Greenwald
Moshe
M
Aizikovich
Alexander
A
Ofer
Dror
D
Byk
Gerardo
G
Gellerman
Garry
G
D020650:Combinatorial Chemistry Techniques; D019992:Databases as Topic; D015195:Drug Design; D008956:Models, Chemical; D008958:Models, Molecular; D019151:Peptide Library; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry*
D019151:Peptide Library; D015363:Quinolones