The Role of Fluorine in Glycomimetic Drug Design.
Chemistry
; 27(7): 2240-2253, 2021 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-32901973
Glycans are well established to play important roles at various stages of infection and disease, and ways to modulate these interactions have been sought as novel therapies. The use of native glycan structures has met with limited success, which can be attributed to their characteristic high polarity (e.g., low binding affinities) and inherently poor pharmacokinetic properties (e.g., short drug-target residence times, rapid renal excretion), leading to the development of 'glycomimetics'. Fluorinated drugs have become increasingly common over recent decades, with fluorinated glycomimetics offering some unique advantages. Deoxyfluorination maintains certain electrostatic interactions, while concomitantly reducing net polarity through 'polar hydrophobicity', improving residence times and binding affinities. Fluorination destabilizes the oxocarbenium transition state associated with metabolic degradation, and can restore exo- and endo-anomeric effects in C-glycosides and carbasugars. Lastly, it has shown great utility in radiotracer development and enhancement of antigenicity in glycan-based vaccines. Owing to synthetic challenges, fluorinated glycomimetics have been somewhat underutilized to date, but methodological improvements will advance their use in glycomimetic drugs.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polisacáridos
/
Diseño de Fármacos
/
Biomimética
/
Materiales Biomiméticos
/
Flúor
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Chemistry
Asunto de la revista:
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Alemania