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Solid-phase/solution-phase combinatorial synthesis of neuroimmunophilin ligands
M Rabinowitz1, P Seneci, T Rossi
1Glaxo Wellcome, Inc., Research Triangle Park, NC 27709, USA. mhr20812@glaxowellcome.com
Bioorganic & Medicinal Chemistry Letters
|June 8, 2000
Summary
A new synthesis method for neuroimmunophilin ligands was created. This approach efficiently produces many compounds for drug discovery using a novel purification technique.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Neuroscience
Background:
- Neuroimmunophilins are crucial targets in neurological research.
- Developing efficient synthesis strategies for novel ligands is essential for drug discovery.
- GPI 1046 serves as a key structural motif for neuroimmunophilin ligands.
Purpose of the Study:
- To develop a novel solid-phase/solution-phase synthesis strategy for neuroimmunophilin ligands.
- To enable the production of multi-milligram quantities of discrete compounds for biological assays.
- To create a scalable and high-throughput method for ligand synthesis and purification.
Main Methods:
- A combined solid-phase esterification and solution-phase pyruvic amide formation strategy was employed.
- The protocol was validated through the synthesis of a library of 880 discrete compounds.
- A novel aqueous liquid/ice extraction system was utilized for high-throughput purification.
Main Results:
- The developed strategy successfully produced multi-milligram quantities of neuroimmunophilin ligands.
- The synthesis protocol was applied to generate a library of 880 distinct compounds.
- The novel extractive purification method proved effective for high-throughput compound isolation.
Conclusions:
- The novel solid-phase/solution-phase strategy offers an efficient route to neuroimmunophilin ligands.
- The high-throughput purification system facilitates rapid compound isolation for screening.
- This approach supports the advancement of drug discovery for neurological targets.