BCPPlus · New directions in bicyclopentane research

New directions in bicyclopentane research

The pharmaceutical industry is increasingly seeking new tactics for the structural modification of drug candidates that avoid problems with metabolic susceptibility, or to improve pharmacokinetic properties. Analogues called 'bioisosteres', which mimic the dimensions and substituent vectors of problematic structural motifs, but which are not themselves subject to the same pharmacological limitations, offer one solution. These are often based on scaffolds that are not found in ‘typical’ drug candidates. Within this growing field, rigid polycycles such as bicyclo[1.1.1]pentane (BCP) are receiving significant attention as arene bioisosteres, as they exhibit similar size and shape. Current methods for BCP synthesis require harsh conditions; this limits product scope and therefore the development of medicinally-relevant compounds. The invention of new methodology to access this motif will revolutionize use of BCPs in the pharmaceutical sector. The knowledge generated from this project will advance our understanding of caged hydrocarbons, transition metal catalysis and photoredox catalysis and will facilitate and accelerate the production of high-value pharmaceutical chemicals bearing BCP motifs. Translation of this research to drug discovery programs will create opportunities for commercialisation, adding substantial value to the biotechnology and pharmaceutical sectors. In addition, this proposal will lead to strong and rewarding national and international collaborations with global pharmaceutical and academic leaders. Objectives: The central objective of the project is to create methodology which will allow for the widespread use of the BCP motif in medicinal and agrochemical industries. Specifically we sought to: Explore general and mild ATRA-based syntheses of BCP derivatives with a particular focus on exploiting photoredox catalysis; Functionalize the bicyclo[1.1.1]pentane ring system, focussing on transition metal and photoredox catalysed transformations; Synthesise novel bicyclo[1.1.1]pentanes analogues of peptidic and non-peptidic drugs and natural product analogues. Conclusions: The methods which we have developed in this project enable easy synthesis to BCP compounds, significantly increasing the accessibility of these compounds in medicinal chemistry. These methodologies are already being utilised in the drug discovery programmes of our industrial collaborators and we anticipate that this research will soon result in new drugs which feature the BCP motif.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз