ABSTRACT
The solid-phase synthesis of a 10,000 member combinatorial library of 1,5-benzodiazepine-2-one derivatives is reported. The 3-amino-1,5-benzodiazepine-2-one scaffold was prepared in solution, and the benzamide nitrogen was used as a point of attachment to the resin. The 5-aniline and 3-amine were then used as points of diversity. A 10,000 member library was synthesized using the Irori directed sorting system, and after analysis of a representative sample from the library, the Irori system was used to remove the compounds of lower purity.
Subject(s)
Anti-Anxiety Agents/chemistry , Benzodiazepinones/chemistry , Benzodiazepinones/chemical synthesis , Amines/chemical synthesis , Amines/chemistry , Amino Acid Sequence , Combinatorial Chemistry Techniques/methods , Drug Design , Dynorphins/chemistry , Ligands , Molecular Sequence Data , Molecular Structure , Structure-Activity RelationshipABSTRACT
A Lead Discovery Library of piperazine-2-carboxamide derivatives was produced for general screening. This paper discloses two novel solid phase synthetic routes used to produce 15,000 single compounds via the Irori directed sorting technique. Computational methods such as reagent clustering and library profiling were used to maximize reagent diversity and optimize pharmacokinetic parameters. The results of a four center pharmacophore analysis revealed the added diversity gained by using two independent synthetic routes.
