Novel Synthetic Options Towards the Manufacture of FXIa Inhibitor

This patent application describes innovative synthetic methods for manufacturing a critical anti-thrombotic pharmaceutical compound. Bristol-Myers Squibb Company and Janssen Pharmaceutica NV have developed highly efficient processes for preparing key intermediates in the synthesis of a factor XIa inhibitor, a compound with significant potential in treating blood clotting disorders.

The Problem

The synthesis of complex pharmaceutical compounds, particularly those with multiple chiral centers and intricate molecular architectures, poses significant challenges in drug manufacturing. Factor XIa inhibitors are valuable therapeutic agents for treating thromboembolic disorders like venous thrombosis and deep vein thrombosis, but their synthesis involves multiple steps that can be inefficient or costly at scale.

Existing synthetic routes often require complex protecting group strategies, inefficient conversions, or hazardous reagents. These limitations can significantly increase manufacturing costs and reduce overall yields, making it difficult to produce sufficient quantities for clinical needs.

What This Invention Does

The inventors have developed multiple improved synthetic routes that provide highly efficient methods for preparing key intermediates in the manufacture of their target factor XIa inhibitor compound. These methods are broadly applicable and can accommodate various substituents on key starting materials, allowing flexibility in synthesis.

By identifying superior synthetic pathways, the inventors have created processes that are more efficient, safer, and potentially more cost-effective than previously known methods. The improved procedures maintain high selectivity and yield while reducing the complexity of the overall synthetic sequence.

Key Features

Efficient Intermediate Synthesis. Novel methods for preparing key intermediates that are broadly applicable across multiple synthetic routes.

Versatile Substituent Compatibility. The disclosed processes can accommodate selected components with a variety of substituent groups.

Improved Manufacturing Routes. Multiple improved processes provide alternative synthetic pathways for industrial-scale production.

Factor XIa Inhibitor Target. Specifically designed for the preparation of compounds useful in treating venous thrombosis and deep vein thrombosis.

Who Is Behind It?

Bristol-Myers Squibb Company and Janssen Pharmaceutica NV are major pharmaceutical companies based in the United States and Belgium respectively. Bristol-Myers Squibb is a leading biopharmaceutical company known for developing innovative medicines, while Janssen Pharmaceutica is part of the Johnson and Johnson family of companies. The patent represents the combined expertise of multiple inventors from both organizations. This application is a divisional of Australian patent application 2020272973, which derives from the international PCT application PCT/US2020/027655, originally filed on 10 April 2020.

Why It Matters

Factor XIa plays a key role in the blood coagulation cascade, particularly in the amplification phase that leads to thrombin generation. As an attractive target for anti-thrombotic therapy, factor XIa inhibitors represent an important class of compounds for treating venous thrombosis, deep vein thrombosis, and potentially other thromboembolic conditions. Improvements in the synthesis of these compounds could significantly reduce manufacturing costs and increase their accessibility to patients who need them.

The IPC classifications (C07D 213/61 for heterocyclic chemistry, C07D 471/18 for macrocyclic compounds, and C07D 401/04 for nitrogen-containing heterocycles) reflect the complex organic chemistry involved. This work demonstrates the ongoing importance of synthetic chemistry innovation in bringing effective pharmaceuticals to market.

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AU 2026201396 was published in the Australian Official Journal of Patents on 19 March 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.

Related Concepts

Factor XIa is a serine protease that amplifies the coagulation cascade, making it an attractive target for anti-thrombotic drugs that may carry a lower bleeding risk than conventional anticoagulants. Inhibiting this factor can reduce clot formation in conditions such as deep vein thrombosis and stroke.

Efficient pharmaceutical synthesis is critical for cost-effective drug manufacturing. Shorter synthetic routes with higher yields reduce raw-material consumption, waste generation, and production cost – all key considerations for bringing a new anticoagulant to a broad patient population.