Escape from planarity in fragment-based drug discovery: A physicochemical and 3D property analysis of synthetic 3D fragment libraries.
Drug Discov Today Technol
; 38: 77-90, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-34895643
ABSTRACT
Fragment-based drug discovery (FBDD) has grown into a well-established approach in the pursuit of new therapeutics. Key to the success of FBDD is the low molecular complexity of the initial hits and this has resulted in fragment libraries that mainly contain compounds with a two-dimensional (2D) shape. In an effort to increase the chemical diversity and explore the impact of increased molecular complexity on the hit rate of fragment library screening, several academic and industrial groups have designed and synthesised novel fragments with a three-dimensional (3D) shape. This review provides an overview of 25 synthetic 3D fragment libraries from the recent literature. We calculate and compare physicochemical properties and descriptors that are typically used to measure molecular three-dimensionality such as fraction sp3 (Fsp3), plane of best fit (PBF) scores and principal moment of inertia (PMI) plots. Although the libraries vary widely in structure and properties, some key common features can be identified which may have utility in designing the next generation of 3D fragment libraries.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bibliotecas de Moléculas Pequenas
/
Descoberta de Drogas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Drug Discov Today Technol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Holanda