Porton Participates in Publishing an OPRD Paper, Demonstrating Strength in Drug Synthesis Technology

The paper focuses on the optimization and development of a commercial synthesis route for the σ-2 receptor modulator CT1812. The first-generation process originates from a pharmaceutical chemistry route, using catechol and ortho-xylene as starting materials, and obtains the target product with 12 steps of reaction, although it has been scaled up to 80kg and used in phase II clinical trials, there are still significant shortcomings:
a) Lengthy steps causing a long production cycle, relatively high cost; part of the reaction steps have safety risks and solvents toxicity problems.
b) Poor selectivity of the key intermediate, a large amount of by-products, and restricted efficiency of scale production.
To resolve the above pain points, the R&D team successfully developed the second-generation process, achieved significant breakthroughs through technical optimization: total yield of straight-chain step increased from 13% to 20.8%, and the production of 94kg API has been successfully completed and applied in phase III clinical trials, which built a solid foundation for the advancement of commercialization of the drug.

As the global leading CDMO corporation, Porton played a key role in the collaboration based on its strong R&D ability and technical platform. Porton has an R&D service platform that covers the drug lifecycle, from process route discovery, optimization to pilot-scale experiment and commercialized production, then to quality research and CMC registration support, providing an end-to-end solution for the innovative drug industry. Especially during the late stage of drug development, Porton has established a systematic process development system centered on the Design of Experiments (DoE). By utilizing development strategies based on Quality by Design (QbD), this system can proactively identify potential risks during process scale-up and ensure a seamless transition of the process from laboratory pilot scale to commercialized production. It provides stable, cost-effective, and compliant process solutions for late-stage drug development. As in this project, the ideal synthesis condition of the intermediate 9 was successfully confirmed through DoE technology, which provided important support for the finalization of the design of second-generation process.

Porton’s metal catalytic technology platform is also an important contributor to this R&D breakthrough. The platform is equipped with a 24-/96 well plate micro-screening system, focusing on the screening and optimization of Pd, Cu catalyzed coupled reactions such as Suzuki, Buchwald, etc. which has the obvious advantage of low sample consumption, high throughput, and high efficiency. In this project, through high-throughput screening of catalysts, solvents, and additives, Porton confirmed the best reaction condition, overcoming the problem of controlling the by-products during the hydrogenation step of alkyne intermediate 13.

The publication of this collaborative paper epitomizes the technical accumulation of Porton in the field of drug synthesis process development. In the future, Porton will continue to cultivate into the core technology fields of biocatalysis, sequential chemistry, crystalline particle engineering, etc. We aim to promote technological innovation in the development of small molecules, peptides, oligonucleotides, and other new types of drugs. We provide one-stop solutions to our global partners with more efficient process development capabilities and more reliable quality management systems, to empower the research and development of innovative medicines and their commercialization, and enabling the public’s early access to good medicines.