Author ORCID Identifier

https://orcid.org/0000-0003-3603-5099

Date of Award

Spring 5-4-2022

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dr. Binghe Wang

Second Advisor

Dr. Maged Henary

Third Advisor

Dr. Kostiantyn Marichev

Abstract

A prodrug is a modified drug molecule having no significant biological activity but converts to the parent drug in the biological system. Conventionally, the prodrug is designed and synthesized by modifying a functional group that serves as a ‘synthetic handle’. However, certain drugs do not have any functional group for easy manipulations. For these drugs, it becomes challenging to design or synthesize a prodrug. Herein, we examine a series of methods for bioreversible derivatization of drugs with a pyridine ring to improve their physicochemical properties including water solubility and conjugation with a targeting moiety. Several model prodrugs were synthesized and examined for solubility, stability, and bioreversible conversion. Three water-soluble prodrug models (BW-HIF-352, BW-HIF-354, and BW-HIF-355) showed significant amount of drug activation under physiological conditions. The same method should be applicable to the preparation of prodrugs of other drugs that contain a pyridine ring or even a quinoline ring.

DOI

https://doi.org/10.57709/29000717

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