1258145-91-3Relevant academic research and scientific papers
Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase
Park, Jaeok,Leung, Chun Yuen,Matralis, Alexios N.,Lacbay, Cyrus M.,Tsakos, Michail,Fernandez De Troconiz, Guillermo,Berghuis, Albert M.,Tsantrizos, Youla S.
, p. 2119 - 2134 (2017/03/17)
The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into nonskeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases. Hit-to-lead optimization of a new series of thienopyrimidine-based monosphosphonates (ThP-MPs) led to the identification of analogs with nanomolar potency in inhibiting hFPPS. Their interactions with the allosteric pocket of the enzyme were characterized by crystallography, and the results provide further insight into the pharmacophore requirements for allosteric inhibition.
Synthesis and antiplasmodial activity of highly active reverse analogues of the antimalarial drug candidate fosmidomycin
Behrendt, Christoph T.,Kunfermann, Andrea,Illarionova, Victoria,Matheeussen, An,Graewert, Tobias,Groll, Michael,Rohdich, Felix,Bacher, Adelbert,Eisenreich, Wolfgang,Fischer, Markus,Maes, Louis,Kurz, Thomas
scheme or table, p. 1673 - 1676 (2011/12/21)
Inhibition of enzymes involved in the nonmevalonate pathway of isoprenoid biosynthesis represents a promising strategy for the development of novel antimalarial agents. A small series of reverse hydroxamate-based fosmidomycin analogues was synthesized and evaluated for their inhibitory activity against the recombinant 1-deoxy-D-xylulose 5-phosphate reductoisomerases (DXRs) of Escherichia coli and Plasmodium falciparum, as well as for their in vitro antiplasmodial activity and cytotoxicity.
