82186-77-4 Usage
Description
Lumefantrine is an antimalarial drug that is used in combination with artemether for the treatment of multi-drug resistant strains of falciparum malaria. It is a derivative of halofantrine and exhibits antimalarial activity. Lumefantrine is very lipophilic and has been reported to inhibit the formation of β-hematin by forming a complex with hemin. Its mechanism of action is not well understood, but it is believed to play a role in inhibiting hemozoin formation. Lumefantrine is a yellow solid and has been developed in China.
Uses
Used in Antimalarial Applications:
Lumefantrine is used as an antimalarial drug for the treatment of malaria. It is particularly effective against multidrug-resistant Plasmodium falciparum strains. The drug is usually classified based on its action against Plasmodia at different stages in their life cycle in the human body.
Used in Artemisinin Combination Therapy:
Lumefantrine is used in combination with artemether, forming a major form of oral artemisinin combination therapy used against uncomplicated P. falciparum malaria. This combination has shown promise for successful treatment of resistant organisms and has not demonstrated evidence of cardiotoxicity.
Used in Research and Development:
Lumefantrine has been used in various research studies, such as:
1. To study its effect on ex-vivo Plasmodium falciparum sensitivity using the tritiated hypoxanthine-based assay as a standard.
2. In the quantification of combined tablet formulation using HPTLC.
3. As a drug molecule in in vitro growth inhibition assay for in vitro B. caballi growth inhibition studies.
Antimalarial drug
Benflumetol and artemether are the widely used antimalarial drugs currently in clinical , they are the main ingredients of the well-known anti-malarial drugs called Compound artemether of Novartis ,which can kill plasmodia asexual, insecticidal rate is high, the cure rate is about 95%, but it is invalid in the pre-erythrocytic stage and gametophyte . Animal experiments suggest it is drug with micro toxicity,but the mutagenic and teratogenic tests are negative. It is mainly used for the treatment of falciparum malaria in clinical, especially for the chloroquine-resistant falciparum malaria treatment.
Physical and Chemical Properties
Yellow crystalline powder, bitter almond smell, tasteless. Soluble in chloroform, slightly soluble in acetone, almost insoluble in alcohol, melting point of 125~131 ℃.
Pharmacokinetics
Oral absorption is slow, elimination is also slow,it can stay a long time in the body . Tmax after administration is 4~5h, t1/2 is 24~72h.
Pharmacokinetics
Bioavailability after oral administration is variable; absorption
is substantially increased by co-administration with food,
particularly
with a high fat content. Peak plasma concentrations
occur after 6–8 h. The elimination half-life is 4–6 days. It
is almost completely protein bound and metabolized mainly
in the liver by CYP3A4.
Dosage
4d therapy: Adults eat 800mg at draught on the first day ,on day 2, 3, 4, each 400mg at draught; children daily take 8mg/kg at draught, and continue for 4d, the first dose is doubled, but the first dose does not exceed the maximum dose of 0.6g.
The above information is edited by the lookchem of Tian Ye.
Adverse reactions
There are no significant adverse reactions, a small number of patients suffer with electrocardiographic Q~T interval transient mild extending.
Precautions
Patients with heart, kidney dysfunction,should use with caution. After symptoms are controlled in patients with malignant malaria and the parasite is killed in the pre-erythrocytic stage ,primaquine can be used to kill gametocytes. It is saved in the dark, sealed, cool and dry place.
Antimicrobial activity
Lumefantrine has marked blood schizonticidal activity against a wide range of plasmodia, including chloroquineresistant P. falciparum. The 50% and 90% effective concentrations (EC50 and EC90) in vitro are similar: <10 and 40 nmol/L, respectively. The racemate and the two enantiomers exhibit similar activities. Blood schizonticidal activity of desbutylbenflumetol is four to five times greater than benflumetol in vitro.
Acquired resistance
Treatment with artemether–lumefantrine can select for polymorphisms
in the P. falciparum pfmdr1 gene. Resistance has
been selected experimentally in murine malaria.
Pharmaceutical Applications
A dichlorobenzylidene derivative given orally in combination
with artemether.
Biochem/physiol Actions
Lumefantrine is is an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.
Clinical Use
Treatment of P. falciparum infections (including mixed infections)
in a fixed-dose combination treatment with artemether.
Side effects
The most common adverse effects in combination with artemether
include headache, dizziness and gastrointestinal disturbances.
Metabolism
Primaquine is almost totally metabolized by CYP3A4 (99%), with the primary metabolite being
carboxyprimaquine. Trace amounts of N-acetylprimaquine plus aromatic
hydroxylation and conjugation metabolites also have been reported.
Check Digit Verification of cas no
The CAS Registry Mumber 82186-77-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,2,1,8 and 6 respectively; the second part has 2 digits, 7 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 82186-77:
(7*8)+(6*2)+(5*1)+(4*8)+(3*6)+(2*7)+(1*7)=144
144 % 10 = 4
So 82186-77-4 is a valid CAS Registry Number.
InChI:InChI=1/C30H32Cl3NO/c1-3-5-13-34(14-6-4-2)19-29(35)28-18-23(33)17-27-25(15-20-7-9-21(31)10-8-20)26-16-22(32)11-12-24(26)30(27)28/h7-12,15-18,29,35H,3-6,13-14,19H2,1-2H3/b25-15-
82186-77-4Relevant articles and documents
Preparation method for benflumetol and matched system thereof
-
, (2020/05/02)
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.
An improved manufacturing process for the antimalaria drug coartem. Part II
Beutler, Ulrich,Fuenfschilling, Peter C.,Steinkemper, Andreas
, p. 341 - 345 (2012/12/31)
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.
