2,6-Difluorophenol as a bioisostere of a carboxylic acid: bioisosteric analogues of gamma-aminobutyric acid.

doi:10.1021/JM980435L

Paper

2,6-Difluorophenol as a bioisostere of a carboxylic acid: bioisosteric analogues of gamma-aminobutyric acid.

Published Jan 28, 1999 · J. Qiu, S. Stevenson, M. J. O'Beirne

Journal of medicinal chemistry

Q1 SJR score

37

Citations

0

Influential Citations

Full textSemantic Scholar

Abstract

3-(Aminomethyl)-2,6-difluorophenol (6) and 4-(aminomethyl)-2, 6-difluorophenol (7) were synthesized in eight and four steps, respectively, starting from 2,6-difluorophenol, to test the potential of the 2,6-difluorophenol moiety to act as a lipophilic bioisostere of a carboxylic acid. Compounds 6 and 7 are potential bioisosteric analogues of gamma-aminobutyric acid (GABA). Substrate studies and inhibition studies were carried out with pig brain gamma-aminobutyric acid aminotransferase; 6 and 7 are very poor substrates, but both inhibit the enzyme, indicating that the 2, 6-difluorophenol moiety appears to be able to substitute for a carboxylic acid to increase the lipophilicity of drug candidates.

In Vitro Study

Study Snapshot

The 2,6-difluorophenol moiety can act as a lipophilic bioisostere of a carboxylic acid, increasing the lipophilicity of drug candidates.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

2,6-Difluorophenol as a bioisostere of a carboxylic acid: bioisosteric analogues of gamma-aminobutyric acid.

Sign up to use Study Snapshot

References

Citations

Highlights on U.S. FDA-approved fluorinated drugs over the past five years (2018-2022).

Fluorine-containing drugs approved by the U.S. FDA over the past five years include 38 for cancer therapy, 12 for infectious diseases, 11 for CNS disorders, and 6 for other diseases.

Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer.

ErSO-DFP, a modified ErSO, shows enhanced selectivity for estrogen receptor positive breast cancer cells and is well-tolerated in rodents, offering a promising new treatment option for ER+ breast cancers.

Analog Design as useful Strategy for Molecular Modification and Drug Design

Analog design is a useful strategy for modifying drug molecules to create new molecules showing chemical and biological similarity to the original model compound, leading to significant advances in pharmaceutical research and drug development.

A Difluoromethylene Linchpin/Synthon: Application in Conjunction with Anion Relay Chemistry (ARC) Permits Ready Access to Diverse Difluoromethylene Scaffolds.

This study presents a novel one-pot strategy for constructing diverse organodifluorine containing compounds using a difluoromethylene linchpin/synthon and anion relay chemistry.

The Influence of Varying Fluorination Patterns on the Thermodynamics and Kinetics of Benzenesulfonamide Binding to Human Carbonic Anhydrase II

Fluorination of benzenesulfonamides to human Carbonic Anhydrase II can lead to complex thermodynamic and kinetic structure-activity relationships, with a higher degree of fluorination not necessarily resulting in higher affinity or more favorable kinetic binding profiles.