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 journalArticle

7 Citations (Scopus)

Abstract

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
Volume19
Issue number33
DOIs
Publication statusPublished - 2012

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Pharmaceutical Chemistry
Metabolites
Pharmaceutical Preparations
Metabolism
Phenacetin
Drug Monitoring
Enzymes
Cytochromes
Acetaminophen
Mixed Function Oxygenases
Foreign Bodies
Aldehydes
Hydroxyl Radical
Cytochrome P-450 Enzyme System
Amines
Pharmacology
Animals
Liver
Monitoring

Keywords

  • 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

  • Molecular Medicine
  • Pharmacology

Cite this

Medicinal chemistry of drugs with active metabolites (N-, O-, and S-desalkylation and some specific oxidative alterations). / Ram, N.; Kalász, H.; Adeghate, E.; Darvas, F.; Hashemi, F.; Tekes, K.

In: Current Medicinal Chemistry, Vol. 19, No. 33, 2012, p. 5683-5704.

Research output: Contribution to journalArticle

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