Medicinal chemistry of drugs with active metabolites (N-, O-, and S-desalkylation and some specific oxidative alterations)

N. Ram, H. Kalász, E. Adeghate, F. Darvas, F. Hashemi, K. Tekes

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)


Metabolic fate plays an important role in the elimination of drugs and other foreign compounds from the body. Metabolism through various enzyme systems, makes the parent compound more hydrophilic, thus, it can be readily excreted from the body. Some active metabolites of drugs are produced following N-, O-, and S-desalkylation. These metabolites are either more or less potent, or as potent as their parent drugs. The removal of alkyl groups from tertiary aliphatic and acyclic amines is carried out by hepatic cytochrome P450 mixed-function oxidase enzymes. Several drugs undergo this process, which yields free hydroxyl-, or amino-groups, in addition to aldehyde from the splitted alkyl group. Metabolism of drugs into clinically active compounds indicates an extra target of therapeutic drug monitoring. Numerical data of logP values show how lipophilicity changes through metabolism to facilitate excretion. The example of phenacetin - paracetamol opened up a way for improving pharmacological effect by the use of a metabolite. This review gives a detailed description of these drugs, their active and major metabolites found in humans or animals, metabolizing cytochrome P450s, and the most recent analytical methods for their determination.

Original languageEnglish
Pages (from-to)5683-5704
Number of pages22
JournalCurrent Medicinal Chemistry
Issue number33
Publication statusPublished - 2012


  • Active metabolites
  • Analysis of active metabolites
  • LogP
  • N-demethylation
  • N-desalkylation
  • N-desethylation
  • O-demethylation
  • O-desethylation
  • S-demethylation
  • Total polar surface area

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


Dive into the research topics of 'Medicinal chemistry of drugs with active metabolites (N-, O-, and S-desalkylation and some specific oxidative alterations)'. Together they form a unique fingerprint.

Cite this