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97 18 Peroxides Despite being strong oxidants and thermally unstable, organic peroxides are occasionally used as drugs. These include the artemisinin-derived antimalarials (Table 16.1) and the anthelmintic ascaridole (Scheme 18.1). One of the metabolic transformations of these compounds includes reductive O – O bond cleavage. O O Ascaridole O O O O H H OH Artenimol t 1/2 1.6 h, F 19% (rat) O O O O H H O Artemotil F 35% (rat) Scheme 18.1 Peroxide-containing drugs. Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and Organic Compounds, First Edition. Florencio Zaragoza D¨ orwald. 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2012 by Wiley-VCH Verlag GmbH & Co. KGaA.

Lead Optimization for Medicinal Chemists (Pharmacokinetic Properties of Functional Groups and Organic Compounds) || Peroxides

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97

18Peroxides

Despite being strong oxidants and thermally unstable, organic peroxides areoccasionally used as drugs. These include the artemisinin-derived antimalarials(Table 16.1) and the anthelmintic ascaridole (Scheme 18.1). One of the metabolictransformations of these compounds includes reductive O–O bond cleavage.

OO

Ascaridole

O

OOO

H

H

OH

Artenimolt1/2 1.6 h, F 19% (rat)

O

OOO

H

H

O

ArtemotilF 35% (rat)

Scheme 18.1 Peroxide-containing drugs.

Lead Optimization for Medicinal Chemists: Pharmacokinetic Properties of Functional Groups and OrganicCompounds, First Edition. Florencio Zaragoza Dorwald. 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2012 by Wiley-VCH Verlag GmbH & Co. KGaA.