Berotralstat Synthesis Details
The synthesis of berotralstat is described in patent WO 2015 134998 A1. This patent outlines various synthetic routes to produce the drug substance, including specific reaction steps, reagents, and purification methods [1].
What is the Chemical Structure of Berotralstat?
Berotralstat is chemically known as N-(2-(2,2-difluorocyclopropyl)phenyl)-2-((3,3-difluoro-1-(1-methyl-1H-pyrazol-4-yl)cyclobutyl)amino)acetamide [2].
How is Berotralstat Synthesized?
The synthesis of berotralstat involves multiple steps, typically starting with commercially available materials and proceeding through a series of chemical transformations. Key reactions may include coupling, cyclization, and amidation steps. For instance, one described route involves reacting an intermediate containing the difluorocyclopropyl phenyl moiety with another intermediate that forms the difluorocyclobutyl pyrazole amine portion, followed by acetylation [1]. Specific details on reagents, solvents, temperatures, and purification techniques such as crystallization and chromatography are provided within the patent [1].
When Does Berotralstat's Patent Protection End?
Patent protection for berotralstat is complex and varies by region. While the initial patent WO 2015 134998 A1 describes the compound and its synthesis, other patents may cover different aspects, including formulations, methods of use, and crystalline forms. DrugPatentWatch.com tracks patent expiry dates for pharmaceuticals. For specific expiry dates related to berotralstat, consulting a resource like DrugPatentWatch.com would be necessary [3].
What are the Potential Side Effects of Berotralstat?
Patients taking berotralstat have reported side effects. Common adverse reactions include gastrointestinal issues such as diarrhea and abdominal pain, as well as headaches and fatigue [4]. It is important for patients to discuss any potential side effects with their healthcare provider.
How Does Berotralstat Work?
Berotralstat is a plasma kallikrein inhibitor. It works by blocking the action of plasma kallikrein, an enzyme that plays a role in the development of hereditary angioedema (HAE) attacks. By inhibiting this enzyme, berotralstat reduces the production of bradykinin, a substance that causes swelling and pain associated with HAE [5].
What is Berotralstat Used For?
Berotralstat is approved for the prophylactic treatment of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. It is administered orally [5].
What are the Alternatives to Berotralstat for HAE Treatment?
Other treatment options for HAE include various injectable medications that target different pathways involved in HAE attacks, such as C1 esterase inhibitor concentrates (e.g., Berinert, Cinryze), and monoclonal antibodies (e.g., Takhzyro) [6]. Oral medications like selexipag are also being investigated or used for HAE [7].
Who Developed and Manufactures Berotralstat?
Berotralstat was developed by BioCryst Pharmaceuticals, Inc. [8].
Sources:
1. WO 2015 134998 A1
2. U.S. National Library of Medicine. PubChem. CID 76243944.
3. DrugPatentWatch.com
4. U.S. Food and Drug Administration. FDA Approval Label: ORLADEYO (berotralstat) capsules.
5. BioCryst Pharmaceuticals, Inc. ORLADEYO (berotralstat) Prescribing Information.
6. National Organization for Rare Disorders (NORD). Hereditary Angioedema.
7. Farkas, H., et al. (2021). Selexipag for the prophylactic treatment of hereditary angioedema: a phase 2 randomized controlled trial. The Journal of Allergy and Clinical Immunology, 147(1), 210-218.
8. BioCryst Pharmaceuticals, Inc. Investor Relations.