title: Approaches for introducing high molecular diversity in scaffolds: fast parallel synthesis of highly substituted 1H-quinolin-4-one libraries.
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.
authors.affiliation: Compugen Ltd, Ashkelon 78785, Israel.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kuznetsov
authors.forename: Sofia
authors.initials: S
authors.lastname: Gorohovsky
authors.forename: Amalia
authors.initials: A
authors.lastname: Levy
authors.forename: Simcha
authors.initials: S
authors.lastname: Meir
authors.forename: Vladimir
authors.initials: V
authors.lastname: Shkoulev
authors.forename: Naim
authors.initials: N
authors.lastname: Menashe
authors.forename: Moshe
authors.initials: M
authors.lastname: Greenwald
authors.forename: Alexander
authors.initials: A
authors.lastname: Aizikovich
authors.forename: Dror
authors.initials: D
authors.lastname: Ofer
authors.forename: Gerardo
authors.initials: G
authors.lastname: Byk
authors.forename: Garry
authors.initials: G
authors.lastname: Gellerman
mesh_terms: 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*
chemical_list: D019151:Peptide Library; D015363:Quinolones