The client in this program is a medium sized biotech with no internal chemistry capacity. Working from a few early hit compounds, the project involved lead generation, optimization and ultimately, selection of a development candidate.
”I want to recognize the team’s work in particular on several multi-gram quantity scale ups over the first half of this year. This includes many compounds in the 1-10 g range and has culminated with the very recent completion of a 100 g batch of one of our lead compounds. This material will enable us to run several key in vivo studies in parallel, and the data may represent an important breakthrough for the program. These scale-ups represent the most critical programs needs and the team has exceeded expectations”
The project involved development of an inhibitor of an epigenetic target for treatment of cancer and inflammatory diseases.
Medicinal chemistry design was driven by the client with input from SYNthesis based on chemical structure where appropriate. Synthetic routes to complex target structures were designed by SYNthesis.
- >1200 compounds registered
- 400+ compounds patented from main lead series.
- Lead analogs achieved up to 1000-fold improvement in potency over early hits.
- PK properties successfully optimized to achieve desirable predicted human dose.
- A lead candidate was selected for development along with two backup candidates. Scalable routes to each were developed, to be utilized in process chemistry campaigns.
Multiple hit start points with different chemical scaffolds were explored in parallel to identify a lead series, which was achieved in the first six months of the collaboration. The chemistry largely involved construction of heterocyclic aromatic core templates and preparation/installation of complex heterocycloalkyl functionality, often containing multiple chiral centres.
Impactful route optimization allowed rapid delivery of samples in 20-50mg quantities with >95% purity for screening and PK studies. This was supported by scale up of key synthetic intermediates to >500g scale.
In vitro tools compounds such as NanoBRET probes and PROTACs were also prepared, enabling exploration of new technologies within the program.
Scale up of a number of identified lead compounds was successfully conducted to deliver up to 100g of >98% purity material for in-vivo studies whist working to aggressive timelines. This was facilitated by process route development.
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Average number of steps per compound
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