Antiviral Agents: 3,5-Disubstituted 1,2,4-Oxadiazole Derivatives and Novel Peptidomimetics Containing Hydroxyethyl Isostere and Imidazolidinone Structures

<p>The search for new compounds with biological activity is the major goal of medicinal research.</p><p>One way to discover new lead compounds is the screening of large compound libraries, followed by the optimization of the found compounds. With this method, <b>A3</b> was recently identified as a lead compound showing activity against a variety of viruses, including influenza. The reoccurrence of seasonal and pandemic influenza makes this disease a major thread to human life and economic productivity.</p><p>This dissertation is concerned with the development of a small library of derivatives exploring possible optimization of the <b>A3</b> scaffold. The presence of an indole moiety is seen as a main reason for stability issues with the lead compound. Therefore, the second goal is the finding of a suitable bioisosteric replacement for this residue.</p><p>Four new lead compounds (<b>SKB-126</b>, <b>SKB-134</b>, <b>SKB-136</b> and <b>SKB-150</b>) have been identified from this library, containing new substitution on the indole moiety as well as replacement of the indole with naphthalene and aromatic urea unit.</p><p>With continuous development in biochemical research, the understanding of biological mechanisms on the cellular level has brought attention to peptides as means to manipulate those mechanisms in order to treat diseases. Peptidomimetics are compounds with behavior similar to that of the peptide they mimic, but typically have structural enhancements that prevent quick metabolism or excretion from the system.</p> <p>A new class of peptidomimetics derived from both imidazolidinones and hydroxyethylene isosteres is described herein. The key step of their synthesis is the opening of a fused ring aziridine with amino acids or small peptides to form an oxazolidinone, followed by rearrangement to the target imidazolidinone. A chain elongation on the resulting diol with a second amino acid or peptide fragment provides the novel peptidomimetics containing hydroxyethylene isosteres and imidazolidinone structures.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry and Biochemistry (Arts and Sciences)

Grantor dc:publisher

Ohio University

Year dc:date

2013

Author dc:creator

• Krake, Susann H.

Contributors dc:contributor

• Bergmeier, Stephen C.

• Chemistry
• Organic Chemistry
• Imidazolidinone
• Peptidomimetic
• Antiviral
• Oxadiazole

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1357572368

OAI identifier oai:identifier

oai:etd.ohiolink.edu:ohiou1357572368