Fragment library design, synthesis and expansion: nurturing a synthesis and training platform

Peter C. Ray; Michael Kiczun; Margaret Huggett; Andrew Lim; Federica Prati; Ian H. Gilbert; Paul G. Wyatt

doi:10.1016/j.drudis.2016.10.005

Fragment library design, synthesis and expansion: nurturing a synthesis and training platform

Peter C. Ray, Michael Kiczun, Margaret Huggett, Andrew Lim, Federica Prati, Ian H. Gilbert (Lead / Corresponding author), Paul G. Wyatt (Lead / Corresponding author)

Research output: Contribution to journal › Review article › peer-review

32 Citations (Scopus)

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Abstract

The availability of suitable diverse fragment- and lead-oriented screening compounds is key for the identification of suitable chemical starting points for drug discovery programs. The physicochemical properties of molecules are crucial in determining the success of small molecules in clinical development, yet reports suggest that pharmaceutical and academic sectors often produce molecules with poor drug-like properties. We present a platform to design novel, high quality and diverse fragment- and lead-oriented libraries with appropriate physicochemical properties in a cost-efficient manner. This approach has the potential to assist the way libraries are constructed by significantly addressing the historical uneven exploration of chemical space for drug discovery. Additionally, this platform can teach undergraduates and graduates about compound library design.

Original language	English
Pages (from-to)	43-56
Number of pages	14
Journal	Drug Discovery Today
Volume	22
Issue number	1
Early online date	26 Oct 2016
DOIs	https://doi.org/10.1016/j.drudis.2016.10.005
Publication status	Published - Jan 2017

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10.1016/j.drudis.2016.10.005

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© 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Accepted author manuscript, 2.04 MBLicence: CC BY-NC-ND

Cite this

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title = "Fragment library design, synthesis and expansion: nurturing a synthesis and training platform",

abstract = "The availability of suitable diverse fragment- and lead-oriented screening compounds is key for the identification of suitable chemical starting points for drug discovery programs. The physicochemical properties of molecules are crucial in determining the success of small molecules in clinical development, yet reports suggest that pharmaceutical and academic sectors often produce molecules with poor drug-like properties. We present a platform to design novel, high quality and diverse fragment- and lead-oriented libraries with appropriate physicochemical properties in a cost-efficient manner. This approach has the potential to assist the way libraries are constructed by significantly addressing the historical uneven exploration of chemical space for drug discovery. Additionally, this platform can teach undergraduates and graduates about compound library design.",

author = "Ray, {Peter C.} and Michael Kiczun and Margaret Huggett and Andrew Lim and Federica Prati and Gilbert, {Ian H.} and Wyatt, {Paul G.}",

note = "This work is part-funded by the MSD Scottish Life Sciences Fund (AL). As part of an ongoing contribution to Scottish Life Sciences, Merck Sharp & Dohme (MSD) (known as Merck & Co., Kenilworth, NJ, USA, in the USA and Canada) has given substantial monetary funding to the Scottish Funding Council (SFC) for distribution via the Scottish Universities Life Sciences Alliance (SULSA) to develop and deliver a high-quality drug discovery research and training program. We would also like to acknowledge the contributions Marina Modric through an EU Leonardo da Vinci work experience grant.",

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AU - Prati, Federica

AU - Gilbert, Ian H.

AU - Wyatt, Paul G.

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AB - The availability of suitable diverse fragment- and lead-oriented screening compounds is key for the identification of suitable chemical starting points for drug discovery programs. The physicochemical properties of molecules are crucial in determining the success of small molecules in clinical development, yet reports suggest that pharmaceutical and academic sectors often produce molecules with poor drug-like properties. We present a platform to design novel, high quality and diverse fragment- and lead-oriented libraries with appropriate physicochemical properties in a cost-efficient manner. This approach has the potential to assist the way libraries are constructed by significantly addressing the historical uneven exploration of chemical space for drug discovery. Additionally, this platform can teach undergraduates and graduates about compound library design.

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DO - 10.1016/j.drudis.2016.10.005

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JO - Drug Discovery Today

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Fragment library design, synthesis and expansion: nurturing a synthesis and training platform

Abstract

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