The specific objectives of this project are to design and synthesize the following: l Congeners of lead compounds having confirmed activity, to enhance activity or potency. 2. Prodrugs with structural modifications that may provide improved pharmacokinetics, altered drug transport, improved bio-availability through increased water solubility, or increased chemical stability. 3. Other altered structures that possess elements- of both congener and prodrug. Modifications of a lead may also include partial structures. 4. Compounds related to natural products, e.g., such as alkaloids, heterocycles, nucleosides, peptides.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Treatment (NCI)
Type
Research and Development Contracts (N01)
Project #
N01CM067259-005
Application #
2852559
Study Section
Project Start
1996-09-30
Project End
2001-09-29
Budget Start
1998-07-30
Budget End
1999-09-29
Support Year
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
072933393
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Kimball, F Scott; Turunen, Brandon J; Ellis, Keith C et al. (2008) Enantiospecific synthesis and cytotoxicity of 7-(4-methoxyphenyl)-6-phenyl-2,3,8,8a-tetrahydroindolizin-5(1H)-one enantiomers. Bioorg Med Chem 16:4367-77
Scott Kimball, F; Himes, Richard H; Georg, Gunda I (2008) Synthesis and evaluation of heteroaromatic 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-ones for cytotoxicity against the HCT-116 colon cancer cell line. Bioorg Med Chem Lett 18:3248-50
Kimball, F Scott; Tunoori, Ashok Rao; Victory, Samuel F et al. (2007) Synthesis, in vitro and in vivo cytotoxicity of 6,7-diaryl-2,3,8,8a-tetrahydroindolizin-5(1H)-ones. Bioorg Med Chem Lett 17:4703-7
Yang, KyoungLang; Blackman, Burchelle; Diederich, Wibke et al. (2003) Formal total synthesis of (+)-salicylihalamides A and B: a combined chiral pool and RCM strategy. J Org Chem 68:10030-9