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Azabicycloalkanes: Synthesis and Applications

Project description

Exploring a new chemical space

Drug discovery usually involves the identification of active substances from natural sources or the rational synthesis of bioactive compounds through combinatorial chemistry. Modification or development of new synthetic methods is an ongoing effort to provide as many solutions as possible to the medicinal chemistry community. The EU-funded ABASynth project focuses on azabicyclic amines predicted to have great applicability considering the ubiquity of amines in bioactive organic molecules. Researchers will employ various chemical approaches to deliver novel functionalisation and molecular properties to azabicycloalkanes. The work is expected to introduce new chemical substituents of biologically relevant heterocycles with a variety of applications.

Objective

Small ring azabicyclic amines are predicted to possess unique molecular properties, but lack of synthetic access has to date prevented their thorough evaluation and deployment in high value functional molecules, including drugs. Much recent attention has focused on small-ring carbocyclic frameworks such as bicyclo[1.1.1]pentanes (BCPs), but analogous azabicyclic compounds are poorly described in the literature, which is surprising given the ubiquity of amines in bioactive organic molecules. A literature screen reveals that azabicyclo[2.2.1]heptanes are equivalent to BCPs in frequency of occurrence, but their [3.1.1] isomers and smaller azabicyclo[2.1.1]hexane relatives are much rarer. Azabicyclo[1.1.1]pentanes are essentially unknown, despite one isomer being an attractive bioisostere of the pyridine ring system. This proposal aims to address this ‘void’ in the bioisostere portfolio by introducing ‘small-ring azabicyloalkanes’ (ABAs) as novel motifs of great potential in drug discovery. As well as representing new bioisosteres for biologically-relevant heterocycles (not limited to pyridines, but also piperidines, pyrrolidines, etc.), ABAs offer new opportunities for drug design in their own right due to the impact of the bicyclic scaffold on amine hybridization. This project will deliver general access to small ring ABAs using a wide variety of novel chemical approaches, explore their functionalization, and demonstrate their application. It will use rational theoretical design to tailor ABA properties and develop structural models. Ultimately, this proposal will access a new domain of chemical space with broad application in organic and medicinal chemistry.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2020

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 212 933,76
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 212 933,76
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