1639810-56-2

Upstream product

• 622-33-3 N-benzyloxyamine 
• 2687-43-6 O-benzylhydoxylamine hydrochloride 
• 79722-21-7 tert-butyl N-(benzyloxy)carbamate 
• 66498-61-1 diethyl (2,3-dibromopropyl)phosphonate 
• 1067-87-4 Diethyl allylphosphonate 

Downstream Products

• 1642790-69-9 (+/-)-diethyl ((1-(benzyloxy)-3-ethyl-2-oxoimidazolidin-4-yl)-methyl)phosphonate 
• 1642790-70-2 (+/-)-diethyl ((1-(benzyloxy)-3-phenyl-2-oxoimidazolidin-4-yl)-methyl)phosphonate 
• 1642790-71-3 (+/-)-diethyl ((1-(benzyloxy)-3-(4-fluorophenyl)-2-oxoimidazolidin-4-yl)methyl)phosphonate 
• 1642790-73-5 (+/-)-diethyl ((1-hydroxy-3-phenyl-2-oxoimidazolidin-4-yl)-methyl)phosphonate 
• 1642790-74-6 (+/-)-diethyl ((1-hydroxy-3-(4-fluorophenyl)-2-oxoimidazolidin-4-yl)methyl)phosphonate 
• 1639810-61-9 (E)-diethyl (3-(1-(benzyloxy)-3-ethylureido)prop-1-en-1-yl)phosphonate 
• 1639810-06-2 (E)-diethyl (3-(1-(benzyloxy)-3-phenylureido)prop-1-en-1-yl)phosphonate 
• 1639809-91-8 (E)-diethyl (3-(1-(benzyloxy)-3-(4-fluorophenyl)ureido)prop-1-en-1-yl)phosphonate 
• 1639810-57-3 (E)-diethyl (3-(1-(benzyloxy)-3-ureido)prop-1-en-1-yl)phosphonate 

Relevant academic research and scientific papers

MEPicides: α,β-Unsaturated Fosmidomycin Analogues as DXR Inhibitors against Malaria

Severe malaria due to Plasmodium falciparum remains a significant global health threat. DXR, the second enzyme in the MEP pathway, plays an important role to synthesize building blocks for isoprenoids. This enzyme is a promising drug target for malaria due to its essentiality as well as its absence in humans. In this study, we designed and synthesized a series of α,β-unsaturated analogues of fosmidomycin, a natural product that inhibits DXR in P. falciparum. All compounds were evaluated as inhibitors of P. falciparum. The most promising compound, 18a, displays on-target, potent inhibition against the growth of P. falciparum (IC50 = 13 nM) without significant inhibition of HepG2 cells (IC50 > 50 μM). 18a was also tested in a luciferase-based Plasmodium berghei mouse model of malaria and showed exceptional in vivo efficacy. Together, the data support MEPicide 18a as a novel, potent, and promising drug candidate for the treatment of malaria.

Fosmidomycin analogues with N-hydroxyimidazole and N-hydroxyimidazolone as a chelating unit

Fosmidomycin has been reported to have many biological activities as an antibacterial and antimalarial, along with being a herbicidal agent. Its unique mode of action involves the inhibition of a key step of the non mevalonate pathway by blockade of a crucial enzyme, the 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), whose expression is present in bacteria, plasmodium parasites and higher plants, but not in mammals. Herein we report the development of fosmidomycin and of FR-900098 constrained analogues belonging to an unusual heterocyclic based complexing subunit involving N-hydroxyimidazoles and cyclic N-hydroxyureas.