1. A Novel "One-Bead Two-Scaffold" Method For Solid-Phase Synthesis Of A Small Molecule Heterocyclic Compound Library And Their Inhibition Of Caspase-3 2. An Efficient Synthesis Approach Of 6,8,9,10-Tetrahydro-1,4,6,10-tetraaza-cyclohepta[b]-naphthalene-7

Combinatorial chemistry has been a powerful tool for the preparation of the largenumber of compounds. Obviously, it benefits the process of lead-compound discoveryand optimization. Combinatorial chemistry integrated combinatorial synthesis, highthroughput analysis and high throughput screening. The combinatorial synthesis issurely fundamental for the high throughput analysis and high throughput screening.Generally, combinatorial synthesis includes solid phase synthesis and solution phasesynthesis.Privileged structures have become a popular theme in medicinal chemistry recently,because of their demonstrating "drug-like" or "lead-like" properties. They are notonly in the structure of launched medicines, but also in the biologically activecompounds which were extensively investigated in laboratories. Actually, theypresent a class of molecules capable of binding to multiple receptors with high affinity.Therefore, the exploration of synthesis of privileged structures may provide morechances for discovery of novel lead compounds.This paper comprises of two parts.PARTâ… A Novel "One-Bead Two-Scaffold" Method for Solid-PhaseSynthesis of A Small Molecule Heterocyclic CompoundLibrary and Their Inhibition of Caspase-3The large numbers of compounds based on a single scaffold in a library have limiteddiversity due to their similar chemical information in three-dimensional space.Efficient synthesis of scaffold-diversity libraries will greatly benefit the process ofhigh throughput generation of "lead-like" compounds. Small molecule heterocycliccompound libraries have attracted much interest for their promising biological andpharmacological activities. Quinoxalinone and benzimidazole are attractive privilegedsubstructures for drug design in medicinal chemistry, because they have been shown to possess significantly biological properties. We developed a novel "One-BeadTwo-Scaffold"("OBTS") method. It can simultaneously and efficiently generate twoscaffolds of small molecule heterocyclic compound of benzimidazole andquinoxalinone with a unique starting material. Obviously, it doubles the scaffolddiversity of library with fewer building blocks, and thus, significantly enhances thelibrary synthetic efficiency. We synthesized approximately 4000 compounds by usingthe solid-phase "split-and-pool" approach and the IRORI sorting system. Afterresynthesis and purification of those hit compounds, we found that 1m,1p,18O,18Q,18U,18W,18Z can inhibit caspase-3.19â…¢,19â…©â…¨,19â…©â…ªwere further confirmed asactive compounds after synthesis of 30 more analogues.PARTâ…¡an Efficient Synthesis Approach of6,8,9,10-Tetrahydro-1,4,6,10-tetraaza-cyclohepta[b]-naphthalene-7-one, a Novel Scaffold IntegratedTwo Privileged StructuresQuinoxaline and 1,5-benzodiazepin-2-one are both attractive privileged structures fordrug design since they have been shown to possess significantly biological activities.A novel structure scaffold 6, 8, 9, 10-tetrahydro-1, 4, 6, 10-tetraaza-cyclohepta[b]-naphthalene-7-one integrated both quinoxalin-2-ol and 1, 5-benzodiazepin-2-onetwo privileged structures. We established synthetic method via a five-step successivereaction using 1,5-difluoro-2,4-dinitro benzene as starting material. This syntheticmethod is highly efficient and offers good purity and yield that is adaptable to makingchemical library for screening against a variety of biological targets. Eighteen novelcompounds were synthesized in this paper.