2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]-9H-fluoren-4-yl]ethan-1-ol

• ChemBase ID: 4445
• Molecular Formular: C30H32Cl3NO
• Molecular Mass: 528.94018
• Monoisotopic Mass: 527.15494769
• SMILES: CCCCN(CCCC)CC(c1c2c3c(cc(cc3)Cl)/C(=C/c3ccc(cc3)Cl)/c2cc(c1)Cl)O
• Canonical SMILES: CCCCN(CC(c1cc(Cl)cc2c1c1ccc(cc1/C/2=C/c1ccc(cc1)Cl)Cl)O)CCCC
• InChI: InChI=1S/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-
• InChIKey: DYLGFOYVTXJFJP-MYYYXRDXSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]-9H-fluoren-4-yl]ethan-1-ol; 2-(dibutylamino)-1-{2,7-dichloro-9-[(4-chlorophenyl)methylidene]-9H-fluoren-4-yl}ethan-1-ol
• IUPAC Traditional name: lumefantrine; 2-(dibutylamino)-1-[(9Z)-2,7-dichloro-9-[(4-chlorophenyl)methylidene]-9H-fluoren-4-yl]ethan-1-ol; 2-(dibutylamino)-1-{2,7-dichloro-9-[(4-chlorophenyl)methylidene]fluoren-4-yl}ethanol
• Brand Name: Coartem
• Synonyms: (9Z)-2,7-Dichloro-9-[(4-chlorophenyl)methylene]-α-[(dibutylamino)methyl]-9H-fluorene-4-methanol; 2-Dibutylamino-1-[2,7-dichloro-9-[1-(4-chlorophenyl)meth-(Z)-ylidene]-9H-fluoren-4-yl]ethanol; Benflumelol; dl-Benflumelol; Benflumetol; Lumefantrine; (Z)-2-(Dibutylamino)-1-(2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl)ethanol; (9Z)-2,7-Dichloro-9-[(4-chlorophenyl)methylene]-?-[(dibutylamino)methyl]-9H-fluorene-4-methanol; CPG-56695; Lumefantrine

Database IDs

• CAS Number: 82186-77-4
• MDL Number: MFCD05662268
• PubChem SID: 160967877; 99443260
• PubChem CID: 6437380

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.101684
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 5.7563324
• LogD (pH = 7.4): 6.838559
• Log P: 9.191258
• Molar Refractivity: 160.8105 cm^3
• Polarizability: 59.880398 Å^3
• Polar Surface Area: 23.47 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 8.34
• LOG S: -7.23
• Solubility (Water): 3.09e-05 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO: ≥20 mg/mL; Methanol
• Apperance: yellow powder; Yellow Solid
• Melting Point: 129-131°C

Safety Information

• Storage Condition: Refrigerator
• Storage Warning: IRRITANT
• German water hazard class: 3
• TSCA Listed: false
• Storage Temperature: room temp

Product Information

• Purity: ≥98% (HPLC); 95+%; 97%
• Application(s): Antimalarial agent
• Empirical Formula (Hill Notation): C30H32Cl3NO

DETAILS

DrugBank - DB06708

• Drug Groups: approved
• Description: Lumefantrine is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with artemether for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas.
• Indication: Lumefantrine and artemether combination therapy is indicated for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum, including malaria acquired in chloroquine-resistant areas. May also be used to treat uncomplicated malaria when the Plasmodium species has not been identified. Indicated for use in adults and children greater than 5 kg.
• Pharmacology: Lumefantrine is a blood schizonticide active against erythrocytic stages of Plasmodium falciparum. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.
• Toxicity: Common side effects of combination artemether/lumefantrine therapy in adults include headache, anorexia, dizziness, and asthenia. Common side effects in children include pyrexia, cough, vomiting, anorexia, and headache. Possible serious adverse effects include QT prolongation, bullous eruption, urticaria, splenomegaly (9%), hepatomegaly (adults, 9%; children, 6%), hypersensitivty reaction, and angioedema.
• Affected Organisms: Plasmodium
• Biotransformation: Extensively metabolized in the liver primarily by cytochrome P450 3A4. The major metabolite found in plasma is desbutyl-lumefantrine.
• Absorption: Food increases absorption.
• Half Life: ~ 4.5 days
• Protein Binding: 99.7% bound
• References: Artemether and Lumefantrine (2010). AHFS Drug Information [Electronic versionb]. Retrieved October 24, 2010.; Artemether/Lumefantrine (2010). DrugPoints? System [Electronic version]. Retrieved October 24, 2010.; Novartis. Coartem (artemether/lumefantrine) tablets prescribing information. East Hanover, NJ; 2010 Feb.
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - L5420

Biochem/physiol Actions
Lumefantrine is is an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.

Toronto Research Chemicals - L474000

Inhibits hemozoin formation. Antimalarial.

REFERENCES

• Artemether and Lumefantrine (2010). AHFS Drug Information [Electronic versionb]. Retrieved October 24, 2010.
• Artemether/Lumefantrine (2010). DrugPoints? System [Electronic version]. Retrieved October 24, 2010.
• Novartis. Coartem (artemether/lumefantrine) tablets prescribing information. East Hanover, NJ; 2010 Feb.
• Kumar, N., et al.: Parasitol Res., 76, 214 (1990)
• Pradines, B., et al.: Antimicrob. Agents Chemother., 43, 418 (1990)
• Chotivanich, K., et al.: J. Infect. Dis., 182, 629 (1990)
• Mutabingwa, T., et al.: Lancet, 365, 1474 (1990)
• Wang, Y. et al., CA, 1982, 97, 28538
• Yang, Q. et al., Yaoxue Xuebao, 1988, 23, 921, (resoln)
• Chinese Pat., 1990, 1 042 535; CA, 114, 6046, (synth)
• Mansor, S.M. et al., J. Chromatogr., B: Biomed. Appl., 1996, 682, 321-325, (hplc)