Hopper, Allen T. published the artcileDiscovery of selective Toxoplasma gondii dihydrofolate reductase inhibitors for the treatment of toxoplasmosis, Related Products of piperazines, the publication is Journal of Medicinal Chemistry (2019), 62(3), 1562-1576, database is CAplus and MEDLINE.
A safer treatment for toxoplasmosis would be achieved by improving the selectivity and potency of dihydrofolate reductase (DHFR) inhibitors, such as pyrimethamine I, for Toxoplasma gondii DHFR (TgDHFR) relative to human DHFR (hDHFR). We previously reported on the identification of meta-biphenyl analog II, designed by in silico modeling of key differences in the binding pocket between TgDHFR and hDHFR. II improves TgDHFR selectivity 6.6-fold and potency 16-fold relative to I. Here, we report on the optimization and structure-activity relationships of this arylpiperazine series leading to the discovery of 5-(4-(3-(2-methoxypyrimidin-5-yl)phenyl)piperazin-1-yl)pyrimidine-2,4-diamine III. III has a TgDHFR IC50 of 1.57 ± 0.11 nM and a hDHFR to TgDHFR selectivity ratio of 196, making it 89-fold more potent and 16-fold more selective than I. III was highly effective in control of acute infection by highly virulent strains of T. gondii in the murine model, and it possesses the best combination of selectivity, potency, and prerequisite drug-like properties to advance into IND-enabling, preclin. development.
Journal of Medicinal Chemistry published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C16H18N2, Related Products of piperazines.
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https://en.wikipedia.org/wiki/Piperazine,
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