An Automated, Open-Source Workflow for the Generation of (3D) Fragment Libraries.
ACS Med Chem Lett
; 14(5): 583-590, 2023 May 11.
Article
em En
| MEDLINE
| ID: mdl-37197454
ABSTRACT
The recent success of fragment-based drug discovery (FBDD) is inextricably linked to adequate library design. To guide the design of our fragment libraries, we have constructed an automated workflow in the open-source KNIME software. The workflow considers chemical diversity and novelty of the fragments, and can also take into account the three-dimensional (3D) character. This design tool can be used to create large and diverse libraries but also to select a small number of representative compounds as a focused set of unique screening compounds to enrich existing fragment libraries. To illustrate the procedures, the design and synthesis of a 10-membered focused library is reported based on the cyclopropane scaffold, which is underrepresented in our existing fragment screening library. Analysis of the focused compound set indicates significant shape diversity and a favorable overall physicochemical profile. By virtue of its modular setup, the workflow can be readily adjusted to design libraries that focus on properties other than 3D shape.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Holanda