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Craig W. Lindsley

Lindsley

Research

The Lindsley research group at Vanderbilt University is a unique environment for graduate and postgraduate training. The primary focus of research in our group is synthetic chemistry (total synthesis and synthetic methodology), drug discovery, and medicinal chemistry. The Lab features state-of-the-art technology, typically found only in major pharmaceutical companies, and a diverse group of scientists: staff synthetic and medicinal chemists, experienced Ph.D. Medicinal Chemists from Big Pharma, staff chromatography specialists and a diverse pool of graduate students pursuing Ph.D.s in Chemistry, Pharmacology and Chemical & Physical Biology.

A major focus of our group is synthetic organic chemistry. Graduate students in chemistry will have the opportunity to pursue the total synthesis of a complex, pharmacologically relevant natural product in order to develop classical synthetic skills. Another area of interest is methodology development in the fields of organocatalysis in order to facilitate library synthesis of key intermediates that can be elaborated towards pharmaceutical targets. Our lab has developed methods to generate enantio-enriched beta-fluoroamines, which can be used to improve pharmokinetic properties of drugable compounds, in addition to completing five total syntheses since October 2006 (carpanone, dispyrin, ciliatimides A-C, 8-epi-lucentamycin A, brevisamide) with many more nearing completion.

All members of our lab will collaborate with other members of the Pharmacology, Drug Metabolism, and Clinical Pharmacology departments to pursue small molecule hits from high throughput screens, perform lead optimization studies to develop structure-activity-relationships (SAR) and ultimately deliver small molecules with acceptable properties to validate novel targets/mechanisms in vivo animal models of target diseases. The molecular targets of interest are kinases, GPCRs, ion channels, nuclear hormone receptors and protein-protein interactions, with an emphasis on allosteric modulation as opposed to classical agonism/antagonism. Therapeutic areas of interest span cancer, neuroscience (schizophrenia, anxiety, pain, sleep, Parkinson's disease) and endocrinology (diabetes, obesity). Students will be exposed to every phase of classical drug discovery. As Director of Medicinal Chemistry in the Vanderbilt Program in Drug Discovery and Director of the Vanderbillt Specialized Chemistry Center (MLPCN), training in my laboratory will be broad and involve organic synthesis, medicinal chemistry, pharmacology and drug metabolism. For many programs in the neuroscience area, students will have the opportunity to also develop radioligands for binding assay development and PET tracers for imaging studies.

Another focus in the Lindsley group is parallel synthesis and the development of new technologies for library synthesis. The lab has state-of-the-art microwave synthesis technology, a mass-directed HPLC purification platform, automated normal and reverse phase chromatography, analytical and preparative chiral HPLC and a large collection of monomers and polymer-supported reagents. There are a number of projects directed at synthesizing libraries of small molecule protein-protein inhibitors, target family-directed libraries and other drug-like small molecule libraries for use in high throughput screening efforts.