Synthesis and Biological Evaluation of Phthalazinone Inhibitors of ...
Synthesis and Biological Evaluation of Phthalazinone Inhibitors of ...
Synthesis and Biological Evaluation of Phthalazinone Inhibitors of ...
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
Figure I. IMPDH reaction scheme<br />
C. parvum’s IMPDH differs from human IMPDH due to a diverged<br />
nicotinamide adenosine dinucleotide (NAD + ) site 4 . This NAD + site has been exploited<br />
in high throughput screens as a potential drug target for C. parvum 5 . These<br />
discoveries have resulted in two previously published series <strong>of</strong> C. parvum IMPDH<br />
inhibitors which exhibit in vitro cell culture model <strong>of</strong> infection 6 . In this work, we<br />
have established a structure-activity relationship <strong>of</strong> phthalazine-based inhibitors<br />
derived from another hit from the same high throughput screening which exhibit<br />
potency in cell culture model <strong>of</strong> infection.<br />
Figure II: CpIMPDH inhibitor identified by HTS<br />
The lead compound (7) exhibited an IC50 <strong>of</strong> 945 nM upon resynthesis.<br />
2
Change language