581106-28-7

Upstream product

• 1186-10-3 diethyl 3-(bromopropyl)phosphonic acid 
• 2687-43-6 O-benzylhydoxylamine hydrochloride 
• 1401988-87-1 tert-butyl benzyloxy(3-(diethoxyphosphoryl)propyl)carbamate 
• 79722-21-7 tert-butyl N-(benzyloxy)carbamate 
• 108-24-7 acetic anhydride 
• 557090-55-8 O-(benzylhydroxylamino)propylphosphonic acid diethyl ester 
• 57943-11-0 N-(diethoxyphosphoryl)-O-benzylhydroxylamine 
• 622-33-3 N-benzyloxyamine 
• 4797-81-3 N-benzyloxyacetamide 
• 15110-17-5 diethyl 3,3-diethoxypropylphosphonate 
• 3986-95-6 diethyl (3-oxopropyl)phosphonate 
• 75-36-5 acetyl chloride 

Downstream Products

• 1350649-61-4 C₂₄H₄₂NO₅P 
• 1350649-62-5 C₂₄H₃₈NO₉P 
• 1350649-63-6 C₂₆H₄₂NO₁₁P 
• 1350649-64-7 C₂₈H₃₀NO₉P 
• 1350649-68-1 C₂₁H₂₄NO₉P 
• 73226-73-0 3-(N-acetyl-N-hydroxyamino)-propylphosphonic acid monosodium salt 
• 1417649-92-3 diethyl 3-(N-(phenethyloxy)acetamido)propylphosphonate 
• 1417649-93-4 diethyl 3-(N-(3-phenylpropoxy)acetamido)propylphosphonate 
• 1417649-94-5 diethyl 3-(N-(4-isopropylbenzyloxy)acetamido)propylphosphonate 
• 1417649-95-6 diethyl 3-(N-(cyclohexylmethoxy)acetamido)propylphosphonate 
• 1417695-46-5 C₁₃H₂₀NO₅P 
• 1417695-47-6 C₁₄H₂₂NO₅P 
• 1417695-48-7 C₁₅H₂₄NO₅P 
• 1417695-49-8 C₁₂H₂₄NO₅P 

Relevant academic research and scientific papers

Synthesis and antiplasmodial activity of novel fosmidomycin derivatives and conjugates with artemisinin and aminochloroquinoline

Malaria, despite many efforts, remains among the most problematic infectious diseases worldwide, mainly due to the development of drug resistance by Plasmodium falciparum. The antibiotic fosmidomycin (FSM) is also known for its antimalarial activity by targeting the nonmevalonate isoprenoid synthesis pathway, which is essential for the malaria parasites but is absent in mammalians. In this study, we synthesized and evaluated against the chloroquine-resistant P. falciparum FcB1/Colombia strain, a series of FSM analogs, derivatives, and conjugates with other antimalarial agents, such as artemisinin (ART) and aminochloroquinoline (ACQ). The biological evaluation revealed four new compounds with higher antimalarial activity than FSM: two FSM-ACQ derivatives and two FSM-ART conjugates, with 3.5–5.4 and 41.5–23.1 times more potent activities than FSM, respectively.

Compounds for inhibiting 1-deoxy-D-xylulose-5-phosphate reductoisomerase

In particular, the compound is effective to inhibit Dxr in Mycobacterium tuberculosis (Mtb). The present invention relates to compounds having general formula (I) or (II) where X is an acidic group, such as carboxylate, phosphonate, sulfate, and tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, preferably 2, 3, or 4. The compounds inhibits 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), particularly Dxr in Mycobacterium tuberculosis (Mtb).

Improved efficacy of fosmidomycin against plasmodium and mycobacterium species by combination with the cell-penetrating peptide octaarginine

Cellular drug delivery can improve efficacy and render intracellular pathogens susceptible to compounds that cannot permeate cells. The transport of physiologically active compounds across membranes into target cells can be facilitated by cell-penetrating peptides (CPPs), such as oligoarginines. Here, we investigated whether intracellular delivery of the drug fosmidomycin can be improved by combination with the CPP octaarginine. Fosmidomycin is an antibiotic that inhibits the second reaction in the nonmevalonate pathway of isoprenoid biosynthesis, an essential pathway for many obligate intracellular pathogens, including mycobacteria and apicomplexan parasites. We observed a strict correlation between octaarginine host cell permeability and its ability to improve the efficacy of fosmidomycin. Plasmodium berghei liver-stage parasites were only partially susceptible to an octaarginine-fosmidomycin complex. Similarly, Toxoplasma gondii was only susceptible during the brief extracellular stages. In marked contrast, a salt complex of octaarginine and fosmidomycin greatly enhanced efficacy against blood-stage Plasmodium falciparum. This complex and a covalently linked conjugate of octaarginine and fosmidomycin also reverted resistance of Mycobacteria to fosmidomycin. These findings provide chemical genetic evidence for vital roles of the nonmevalonate pathway of isoprenoid biosynthesis in a number of medically relevant pathogens. Our results warrant further investigation of octaarginine as a delivery vehicle and alternative fosmidomycin formulations for malaria and tuberculosis drug development. Copyright

Design of potential bisubstrate inhibitors against Mycobacterium tuberculosis (Mtb) 1-deoxy-d-xylulose 5-phosphate reductoisomerase (Dxr)-evidence of a novel binding mode

In most bacteria, the nonmevalonate pathway is used to synthesize isoprene units. Dxr, the second step in the pathway, catalyzes the NADPH-dependent reductive isomerization of 1-deoxy-d-xylulose-5-phosphate (DXP) to 2-C-methyl-d-erythritol-4-phosphate (MEP). Dxr is inhibited by natural products fosmidomycin and FR900098, which bind in the DXP binding site. These compounds, while potent inhibitors of Dxr, lack whole cell activity against Mycobacterium tuberculosis (Mtb) due to their polarity. Our goal was to use the Mtb Dxr-fosmidomycin co-crystal structure to design bisubstrate ligands to bind to both the DXP and NADPH sites. Such compounds would be expected to demonstrate improved whole cell activity due to increased lipophilicity. Two series of compounds were designed and synthesized. Compounds from both series inhibited Mtb Dxr. The most potent compound (8) has an IC50 of 17.8 μM. Analysis shows 8 binds to Mtb Dxr via a novel, non-bisubstrate mechanism. Further, the diethyl ester of 8 inhibits Mtb growth making this class of compounds interesting lead molecules in the search for new antitubercular agents.

COMPOUNDS FOR INHIBITING 1- DEOXY-D-XYLULOSE- 5 - PHOSPHATE REDUCTOISOMERASE

[0082] In particular, the compound is effective to inhibit Dxr in Mycobacterium tuberculosis (Mtb). The present invention relates to compounds having general formula (I) or where X is an acidic group, such as carboxylate, phosphonate, sulfate, and tetrazole; Ar is a substituted or unsubstituted aromatic or heteroaromatic group; and n is 0, 1, 2, 3, or 4, preferably 2, 3, or 4. The compounds inhibits l-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), particularly Dxr in Mycobacterium tuberculosis (Mtb).

Synthesis of antimalarial compounds fosmidomycin and FR900098 through N- or P-alkylation reactions

Two straightforward and convenient routes for the synthesis of the antimalarial agents FR900098 and fosmidomycin are described. In the key steps N- or P-alkylation reactions are used. The best overall yields of FR900098 and fosmidomycin in 15 mmol scale a

Growth inhibition of Mycobacterium smegmatis by prodrugs of deoxyxylulose phosphate reducto-isomerase inhibitors, promising anti-mycobacterial agents

Since Mycobacterium tuberculosis sets up several multiple anti-tuberculosis drug resistance mechanisms, development of new drugs with innovative target is urgent. The methylerythritol phosphate pathway (MEP) involved in the biosynthesis of essential metab

Antibacterial and antitubercular activity of fosmidomycin, FR900098, and their lipophilic analogs

The nonmevalonate pathway (NMP) of isoprene biosynthesis is an exciting new route toward novel antibiotic development. Inhibitors against several enzymes in this pathway are currently under examination. A significant liability of many of these agents is p

Double ester prodrugs of FR900098 display enhanced in-vitro antimalarial activity

Fosmidomycin and FR900098 are inhibitors of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR; IspC), a key enzyme of the mevalonate-independent isoprenoid biosynthesis pathway. We have determined the in-vitro antimalarial activity of two double ester prodrugs 2, 3 in direct comparison with the unmodified FR900098 1 against intraerythrocytic forms of Plasmodium falciparum. Temporarily masking the polar properties of the phosphonate moiety of the DXR inhibitor FR900098 1 enhanced not only its oral bioavailability but also the intrinsic activity of this series against the parasites.

Alkoxycarbonyloxyethyl ester prodrugs of FR900098 with improved in vivo antimalarial activity

FR900098 represents a derivative of the new antimalarial drug fosmidomycin with enhanced activity. The mechanism of action is the inhibition of the 1-desoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent