- An improved manufacturing process for the antimalaria drug coartem. Part II
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The manufacturing process for lumefantrine, 2, one of the two active principles in the fixed-dose combination of the anti-malarial drug Coartem, was reworked. For the conversion of 2-chloro-1-(2,7-dichloro-9H-fluoren-4-yl) ethanone, 5, to 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol, 8, a onepot process was developed that eliminated isolation of the epoxide 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane, 7. Significant increase in throughput was achieved by applying new reaction and crystallization conditions for the Knoevenagel condensation of 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl) ethanol, 8, to 2-dibutylamino-1-{2,7-dichloro-9-[1-(4-chlorophenyl)meth-(Z)- ylidene]-9H-fluoren-4-yl}ethanol, 2.
- Beutler, Ulrich,Fuenfschilling, Peter C.,Steinkemper, Andreas
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- Design, synthesis, molecular docking, and biological evaluation of novel selenium containing lumefantrine analogues
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A new series of 1-(9-benzylidene-2,7-dichloro-9H-fluoren-4-yl)-2-(methylselanyl)ethanol was synthesized by a simple Knoevenagel condensation of 1-(2,7-dichloro-9H-fluoren-4-yl)-2-(methylselanyl)ethanol with different substituted aromatic aldehydes in basic media. These synthesized compounds were confirmed on the basis of their elemental analyses, infrared (IR), 1H NMR, 13C NMR, and mass spectral data and screened for the antibacterial and antifungal activity. The preliminary antibacterial and antifungal screening revealed that the compounds 8c (dichloro), 8d (fluoro), 8e (chloro), 8i (methoxy), and 8l (methyl) displayed moderate to good activity. The antibacterial results of these compounds were further supported by in silico molecular docking studies, for the inhibition of Escherichia coli MurB enzyme (PDB code: 2MBR), wherein they showed higher binding energy and good affinity towards the active pocket of the enzyme compared with that of the standard drug Ciprofloxacin. Thus, the plausible mechanism of their antibacterial activity was owed to their inhibitory action of the bacterial MurB enzyme.
- Hegde, Hemant,Nayak, Soukhyarani Gopal,Poojary, Boja,Purushotham, Nikil,Puthran, Divyaraj,Rasheed, Mohammed Shafeeulla
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- Preparation method for benflumetol and matched system thereof
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The invention belongs to the field of benflumetol, and relates to preparation and a system for the benflumetol, in particular to a preparation method for the benflumetol and a matched system thereof.The preparation method for the benflumetol is completed by sequentially through bulk drugs, a plurality of intermediates and the benflumetol. The matched system for the preparation method sequentiallycomprises an intermediate I matched system, an intermediate II matched system, an intermediate IV matched system, an intermediate V matched system and a benflumetol matched system. According to the invention, overall preparation is simple, reasonable and highly-efficient; the required time is greatly shortened; and exploration of industrial production conditions of the benflumetol is completed.
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