The KU Center for Excellence in Chemical Methodologies and Library Development (KU CMLD), now in its fifth year of operation, has firmly established itself as a resource for parallel synthesis of chemical libraries in the US Midwest. In the previous funding period, vital cores for library synthesis as well as library design, analysis, and purification (LDAP) were established. The synthesis core has facilitated library synthesis by providing technology and library expertise to the group of CMLD researchers, while the LDAP core established protocols for in silico evaluation/database maintenance and the mass-directed purification of compounds. The infrastructure made possible through the CMLD program has also benefited the larger scientific community by providing these critical services to researchers outside the CMLD grant per se (e.g., to several groups maintaining separate Pilot Scale Library programs). Following a period of growth, the impact of the KU CMLD center has been established through ca. 60 scientific publications, steadily increasing submission of high-quality compounds to the Molecular Libraries Small Molecule Repository (MLSMR), and biological validation through collaborations with the MLSCN and eight additional biological evaluators that have yielded novel hits from various CMLD research programs. The present application for renewal of the KU CMLD presents programs that will build on its existing strengths and bring the program into new directions. Consistent with its adopted mission of enabling library synthesis as broadly as possible, a series of projects involving seven investigators at four academic institutions is described. Three of the four projects address the synthetic challenges inherent in library construction. These range from C-H functionalization reactions of phenols to Pd-promoted multicomponent reactions to the strategic deployment of a sulfonamide-forming """"""""click"""""""" reaction. The fourth project concerns the development of protocols and technology for carrying out microwave-assisted flow synthesis. Finally, we stand firm in our commitment to provide novel compounds to the MLSMR at the estimated rate of 1800 compounds/year and to follow up on our chemical methodology work by doing all that we can to ensure our compounds will have a positive impact on biomedical science.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM069663-10
Application #
8318259
Study Section
Special Emphasis Panel (ZGM1-PPBC-3 (CL))
Program Officer
Fabian, Miles
Project Start
2003-09-30
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2012
Total Cost
$1,734,421
Indirect Cost
$681,073
Name
University of Kansas Lawrence
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
076248616
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Faisal, Saqib; Maity, Pradip K; Zang, Qin et al. (2016) Application of Silica-Supported Alkylating Reagents in a One-Pot, Sequential Protocol to Diverse Benzoxathiazepine 1,1-Dioxides. ACS Comb Sci 18:387-93
Gowthaman, Ragul; Miller, Sven A; Rogers, Steven et al. (2016) DARC: Mapping Surface Topography by Ray-Casting for Effective Virtual Screening at Protein Interaction Sites. J Med Chem 59:4152-70
Gold, Ben; Smith, Robert; Nguyen, Quyen et al. (2016) Novel Cephalosporins Selectively Active on Nonreplicating Mycobacterium tuberculosis. J Med Chem 59:6027-44
Faisal, Saqib; Maity, Pradip K; Zang, Qin et al. (2016) Synthesis of High-Load, Hybrid Silica-Immobilized Heterocyclic Benzyl Phosphate (Si-OHBP) and Triazolyl Phosphate (Si-OHTP) Alkylating Reagents. ACS Comb Sci 18:394-8
Chandrasoma, Nalin; Pathmanathan, Sivadarshini; Buszek, Keith R (2015) A Practical, Multi-gram Synthesis of (±)-Herbindole A, (±)-Herbindole B, and (±)-Herbindole C from a Common Intermediate via 6,7-Indole Aryne Cycloaddition and Pd(0)-Catalyzed Cross-Coupling Reactions. Tetrahedron Lett 56:3507-3510
He, Shanshan; Jain, Prashi; Lin, Billy et al. (2015) High-Throughput Screening, Discovery, and Optimization To Develop a Benzofuran Class of Hepatitis C Virus Inhibitors. ACS Comb Sci 17:641-52
Frankowski, Kevin J; Liu, Ruzhang; Milligan, Gregory L et al. (2015) Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization. Angew Chem Int Ed Engl 54:10555-8
Loh, Joanna K; Asad, Naeem; Samarakoon, Thiwanka B et al. (2015) Modular, One-Pot, Sequential Aziridine Ring Opening-S(N)Ar Strategy to 7-, 10-, and 11-Membered Benzo-Fused Sultams. J Org Chem 80:9926-41
Maity, Pradip K; Faisal, Saqib; Rolfe, Alan et al. (2015) Silica-Supported Oligomeric Benzyl Phosphate (Si-OBP) and Triazole Phosphate (Si-OTP) Alkylating Reagents. J Org Chem 80:9942-50
Painter, Thomas O; Kaszas, Krisztian; Gross, Jacklyn et al. (2014) Constrained TRPV1 agonists synthesized via silver-mediated intramolecular azo-methine ylide cycloaddition of α-iminoamides. Bioorg Med Chem Lett 24:963-8

Showing the most recent 10 out of 204 publications