Halogen atoms in the modern medicinal chemistry: hints for the drug design

Hernandes, Marcelo; Cavalcanti, Suellen Melo; Moreira, Diogo Rodrigo; de Azevedo Junior, Walter; Leite, Ana Cristina

doi:10.2174/138945010790711996

Cited by 723Crystallography and molecular interactionsComputational Drug Discovery MethodsVanadium and Halogenation Chemistry

Halogen atoms in the modern medicinal chemistry: hints for the drug design

Hernandes, Marcelo, Cavalcanti, Suellen Melo, Moreira, Diogo Rodrigo, de Azevedo Junior, Walter, Leite, Ana Cristina·2010·Current Drug Targets

DOI 10.2174/138945010790711996

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Abstract

A significant number of drugs and drug candidates in clinical development are halogenated structures. For a long time, insertion of halogen atoms on hit or lead compounds was predominantly performed to exploit their steric effects, through the ability of these bulk atoms to occupy the binding site of molecular targets. However, halogens in drug - target complexes influence several processes rather than steric aspects alone. For example, the formation of halogen bonds in ligand-target complexes is now recognized as a kind of intermolecular interaction that favorably contributes to the stability of ligand-target complexes. This paper is aimed at introducing the fascinating versatility of halogen atoms. It starts summarizing the prevalence of halogenated drugs and their structural and pharmacological features. Next, we discuss the identification and prediction of halogen bonds in protein-ligand complexes, and how these bonds should be exploited. Interesting results of halogen insertions during the processes of hit-to-lead or lead-to-drug conversions are also detailed. Polyhalogenated anesthetics and protein kinase inhibitors that bear halogens are analyzed as cases studies. Thereby, this review serves as one guide for the virtual screening of libraries containing halogenated compounds and may be a source of inspiration for the medicinal chemists.

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From a synthesis point-of-view, the emergence of brorphine analogues differing in the halogen substituent seems not only feasible (only involving a one-step procedure), but may actually be likely, as halogenation is an important tool in drug optimization.
“Specifically, from a synthesis point-of-view, the emergence of brorphine analogues differing in the halogen substituent seems not only feasible (only involving a one-step procedure), but may actually be likely, as halogenation is an important tool in drug optimization (Hernandes et al., 2010; Kurczab et al., 2019; Xu et al., 2014).”
From Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization (2024) · cites this paper as Hernandes et al., 2010

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Authors: Hernandes, M., Cavalcanti, S. M., Moreira, D. R., de Azevedo Junior, W., & Leite, A. C.
Affiliations: Universidade Federal de Pernambuco (BR)
Corresponding author: Leite, Ana Cristina
ORCID: Hernandes, Marcelo
Moreira, Diogo Rodrigo
Leite, Ana Cristina
Venue: Current Drug Targets
Publisher: Bentham Science Publishers Ltd.
Published: 2010-03-01
Volume: 11
Issue: 3
Pages: 303-314
ISSN: 1389-4501 (ISSN-L)
DOI: 10.2174/138945010790711996
OpenAlex: W2105058945
Cited by: 723
References: 76
Citations by year: 2026: 53 · 2025: 70 · 2024: 71 · 2023: 57 · 2022: 58 · 2021: 66 · 2020: 54 · 2019: 65 · 2018: 31 · 2017: 32 · 2016: 34 · 2015: 27 · 2014: 29 · 2013: 32 · 2012: 25
FWCI: 17.58
Type: journal article
Language: en
Open access: closed
Locations: Current Drug Targets (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Crystallography and molecular interactions
Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
Physical Sciences › Chemistry › Inorganic Chemistry › Vanadium and Halogenation Chemistry
Keywords: halogen bonding, hit-to-lead optimization, protein-ligand complex, protein kinase inhibitors, drug design
MeSH terms: Animals, Binding Sites, Chemistry, Pharmaceutical, Halogens, Humans, Ligands, Models, Molecular, Protein Binding, Drug Design, Drug Delivery Systems

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Halogen atoms in the modern medicinal chemistry: hints for the drug design

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