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Design and Synthesis of Pyrrolidine-based Fragments That Sample Three-dimensional Molecular Space.

ABSTRACT: Fragment-based drug discovery (FBDD) is a well-established technology for lead compound generation in drug discovery. As this technology has evolved, the design of fragments for screening has also evolved to engender not just an understanding of the role of modulating the physicochemical properties of fragments (Rule of Three, Ro3) but also the importance and implications of incorporating shape and, in particular, 3D characteristics into fragments. Herein, we describe the design and synthesis of pyrrolidine-based fragments with good fragment-like (Ro3) physicochemical properties that effectively sample three-dimensional molecular space.

SUBMITTER: Garner P

PROVIDER: S-EPMC6511948 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Design and Synthesis of Pyrrolidine-based Fragments That Sample Three-dimensional Molecular Space.

Garner Philip P Cox Philip B PB Rathnayake Upendra U Holloran Nicholas N Erdman Paul P

ACS medicinal chemistry letters 20190412 5

Fragment-based drug discovery (FBDD) is a well-established technology for lead compound generation in drug discovery. As this technology has evolved, the design of fragments for screening has also evolved to engender not just an understanding of the role of modulating the physicochemical properties of fragments (Rule of Three, Ro3) but also the importance and implications of incorporating shape and, in particular, 3D characteristics into fragments. Herein, we describe the design and synthesis of ...[more]

PMID: 31098004

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