Fragment‐Based Drug Design: Considerations for Good ADME Properties

LiGen: A High Performance Workflow for Chemistry Driven de Novo Design

“…Therefore, computer programs have been actively sought during the past two decades to help (medicinal) chemists to find the best local solutions in terms of pharmacological properties, chemical feasibility, innovation, and patentability. As a result, several molecular de novo programs, such as LUDI, LEGEND, LeapFrog, LigBuilder 2, SPROUT, , HOOK, PRO-LIGANDS, − and DOGS have been developed and thorough reviews of the de novo programs are available. ,− Despite several successful applications having been reported, many problems eventually prevented molecular de novo design approaches to become established tools in drug design, and, in fact, methods like virtual screening and molecular docking received higher attention, either in terms of successful applications or widespread use. The most common problems associated with these early de novo design methods are the following: (i) producing chemically invalid structures or structures that do not have drug-like properties; (ii) poor synthetic accessibility of the suggested ligand; (iii) low structural diversity; (iv) low potential for parallel synthesis applications (a part when combinatorial chemistry is directly addressed); (v) generally low throughput if compared to docking programs.…”