Synthesis of Congeners and Prodrugs

Cushman, Mark S.

Abstract

The objectives of this project are to design and synthesize the following: (a) Congeners of lead compounds having confirmed activity, to enhance activity or potency; (b) Prodrugs with structural modifications that may provide altered pharmacokinetics, altered drug transport, improved bio-availability through increased water solubility, or increased chemical stability; (c) Other altered structures that possess elements of both congener and prodrug. Modifications of a lead may also include partial structures; and (d) Compounds related to natural products, e.g., alkaloids, heterocycles, nucleosides, peptides, etc. Active leads may also include metal complexes.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: Division of Cancer Treatment (NCI)
• Type: Research and Development Contracts (N01)
• Project #: N01CM017513-000
• Application #: 3609227
• Project Start: 1991-06-30
• Project End: 1994-06-29
• Budget Start: 1991-06-30
• Budget End: 1992-06-29
• Fiscal Year: 1991

Institution

• Name: Purdue University North Central Campus
• Type: Schools of Nursing
• City: Westville
• State: IN
• Country: United States
• Zip Code: 46391

Publications

Cushman, M; Casimiro-Garcia, A; Hejchman, E et al. (1998) New alkenyldiarylmethanes with enhanced potencies as anti-HIV agents which act as non-nucleoside reverse transcriptase inhibitors. J Med Chem 41:2076-89

Keyes, R F; Golebiewski, W M; Cushman, M (1996) Correlation of anti-HIV potency with lipophilicity in a series of cosalane analogs having normal alkenyl and phosphodiester chains as cholestane replacements. J Med Chem 39:508-14

Cushman, M; Golebiewski, W M; Graham, L et al. (1996) Synthesis and biological evaluation of certain alkenyldiarylmethanes as anti-HIV-1 agents which act as non-nucleoside reverse transcriptase inhibitors. J Med Chem 39:3217-27

Golebiewski, W M; Keyes, R F; Cushman, M (1996) Exploration of the effects of linker chain modifications on anti-HIV activities in a series of cosalane analogues. Bioorg Med Chem 4:1637-48

Cushman, M; Golebiewski, W M; Pommier, Y et al. (1995) Cosalane analogues with enhanced potencies as inhibitors of HIV-1 protease and integrase. J Med Chem 38:443-52

Cushman, M; Golebiewski, W M; McMahon, J B et al. (1994) Design, synthesis, and biological evaluation of cosalane, a novel anti-HIV agent which inhibits multiple features of virus reproduction. J Med Chem 37:3040-50

Cushman, M; Sherman, P (1992) Inhibition of HIV-1 integration protein by aurintricarboxylic acid monomers, monomer analogs, and polymer fractions. Biochem Biophys Res Commun 185:85-90