Artemether

One of two molecules for this week.
July 30, 2018
We are key players in the struggle to develop effective malaria medicines.
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Figure 1: Artemether
Image of Artemether 3D Image of Artemether
Figure 2: Artesunate

Artemisinin is a venerable malaria drug that was introduced more than 40 years ago. It was the Molecule of the Week for December 12, 2005.

Artemisinin is an excellent remedy for malaria. For many years, however, its supply has been unpredictable. The sole source of the drug is the sweet wormwood plant (Artemisia annua) that grows in Southeast Asia; but its production cycle is vicious. Farmers grow the plant only when prices are high; the inevitable oversupply lowers prices and production drops, raising prices again.

As a result, medicinal researchers sought to synthesize an artemisinin precursor that would ensure a constant supply of the drug at lower cost than agricultural artemisinin. Sanofi (Gentilly, France) developed a synthesis of artemether (Figure 1), which it commercialized in 2013. Unfortunately, the project failed because the semisynthetic artemisinin could not be produced less expensively than the farmed product.

Since then, drug researchers concentrated on improving the yield of artemisinin and its derivatives from A. annua. For example, the leaves of the plant contain as much dihydroartemisinic acid (DHAA) as artemisinin. Earlier this year, Kerry Gilmore and Peter H. Seeberger at Max Planck Institute of Colloids and Interfaces (Potsdam, Germany) reported that crude extracts of A. annua can be fed into a photochemical flow reactor to produce artemisinin, artemether, and a third active pharmaceutical ingredient, artesunate (Figure 2).

Artesunate turns out to be a particularly attractive malaria drug. It is much more water-soluble than artemisinin, so it can be taken by mouth* or by injection. It is safe and well-tolerated by adults and children. Its success has earned it a place in the World Health Organization's List of Essential Medicines.

*But overdoses can be harmful; see hazard information table.

 

Artemether hazard information

GHS classification**: acute toxicity,oral, category 4
H302—Harmful if swallowedChemical Safety Warning

**Globally Harmonized System of Classification and Labeling of Chemicals. Explanation of pictograms.

Artesunate hazard information

GHS classification: acute toxicity,oral, category 4
H302—Harmful if swallowedChemical Safety Warning
GHS classification: acute toxicity,dermal, category 4 
H312—Harmful in contact with skinChemical Safety Warning
GHS classification: acute toxicity,inhalation, category 4
H332—Harmful if inhaledChemical Safety Warning

Artemether fast facts

CAS Reg. No.71963-77-4
Molar mass298.37 g/mol
Empirical formulaC16H26O5
AppearanceWhite to pale yellow crystals or powder
Melting point86–90 ºC
Water solubility12 mg/L (est.)

Artesunate fast facts

CAS Reg. No.88495-63-0
Molar mass384.42 g/mol
Empirical formulaC19H28O8
AppearanceWhite crystals or powder
Melting point140–142 ºC 
Water solubility680 mg/L

MOTW update: 
July 1, 2024

Artemether1 is a precursor to the malaria drug artemisinin2 that was developed in the 2010s; but it was abandoned because it is more expensive than natural artemisinin.

In June, Qi-qun Tang at Fudan University (Shanghai) and coauthors there and at other Chinese universities described a potential new use for artemether. They discovered that the compound could be the first effective treatment for polycystic ovary syndrome (PCOS), a widespread endocrine disorder that affects ≈10% of reproductive-age women. In a pilot clinical study of 19 women with PCOS, most of the subjects exhibited fewer symptoms of the syndrome and had more regular menstrual cycles.

1. CAS Reg. No. 71963-77-4.
2. CAS Reg. No. 63968-64-9.

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