(The) synthesis of small molecule library using diagonal combinatorial chemistry

Abstract

Recent trends in search for novel pharmaceutical agents have focused on the preparation of small molecule libraries as potential sources of new lead compounds for drug discovery. Several powerful chemical and biological techniques have been developed for this purpose. This thesis presents an advanced method of constructing combinatorial library, which was demonstrated by generating twenty-fivecompounds through reductive amination with a set of five aldehyde derivatives and a set of five secondary amines. It was presented as three sets of subraries in which each of the reagent cumulatively reacted with the corresponding substrates as normal-diagonal,reversed-diagonal and crossed-diagonalmethods in order to deduced the most active compound exactly and efficiently. This diagonal library could provide intrinsic effectiveness that had never been favored in the orthogonal or indexed library known. The diagonal library was designed to have four approaching directions within the matrix, while conventional techniques had only two approaching directions. Thereby, we could improve the possibility of finding true active compound discovery because they had intrinsically acquired additional checking means. As a result, we could reduce the inexactness that associated with surveying true lead compound from libraries.