Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns

Nicola Luise; Paul Wyatt

doi:10.1002/chem.201801313

Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns

Nicola Luise, Paul Wyatt (Lead / Corresponding author)

Drug Discovery Unit

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

433 Downloads (Pure)

Abstract

Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. We report the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed.

Original language	English
Pages (from-to)	10443-10451
Number of pages	9
Journal	Chemistry: a European Journal
Volume	24
Issue number	41
Early online date	7 May 2018
DOIs	https://doi.org/10.1002/chem.201801313
Publication status	Published - 20 Jul 2018

Keywords

Fragment-based drug discovery
synthetic methods
polar small molecules
pyrazole
fused-ring systems
drug discovery
heterocycles

ASJC Scopus subject areas

General Chemistry

Access to Document

10.1002/chem.201801313

Author Accepted ManuscriptAccepted author manuscript, 880 KB
Supporting Information Accepted author manuscript, 11.7 MB

To Design and Develop Semi-Saturated and Unsaturated Bicyclic Heterocycles for Fragment-Based Drug Discovery (FBDD) Campaigns
Luise, N. (Author), Wyatt, P. (Supervisor), 2019
Student thesis: Doctoral Thesis › Doctor of Philosophy

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Cite this

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title = "Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns",

abstract = "Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. We report the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed.",

keywords = "Fragment-based drug discovery, synthetic methods, polar small molecules, pyrazole, fused-ring systems, drug discovery, heterocycles",

author = "Nicola Luise and Paul Wyatt",

note = "We thank the School of Life Sciences, University of Dundee and the Nicholl-Lindsay Studentship for supporting our research.",

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journal = "Chemistry: a European Journal",

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T1 - Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns

AU - Luise, Nicola

AU - Wyatt, Paul

N1 - We thank the School of Life Sciences, University of Dundee and the Nicholl-Lindsay Studentship for supporting our research.

PY - 2018/7/20

Y1 - 2018/7/20

N2 - Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. We report the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed.

AB - Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. We report the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed.

KW - Fragment-based drug discovery

KW - synthetic methods

KW - polar small molecules

KW - pyrazole

KW - fused-ring systems

KW - drug discovery

KW - heterocycles

U2 - 10.1002/chem.201801313

DO - 10.1002/chem.201801313

M3 - Article

C2 - 29732638

SN - 0947-6539

VL - 24

SP - 10443

EP - 10451

JO - Chemistry: a European Journal

JF - Chemistry: a European Journal

IS - 41

ER -

Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns

Abstract

Keywords

ASJC Scopus subject areas

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Student theses

To Design and Develop Semi-Saturated and Unsaturated Bicyclic Heterocycles for Fragment-Based Drug Discovery (FBDD) Campaigns

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