What is WO 2003 077914 A1 about?
The patent application WO 2003 077914 A1 describes a process for synthesizing binimetinib, a MEK inhibitor used in cancer treatment [1].
How is binimetinib synthesized according to the patent?
The patent details specific chemical reactions and intermediate compounds involved in producing binimetinib. One disclosed synthetic route involves the preparation of a key intermediate, (S)-N-(3-amino-1-hydroxypropyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxamide [1]. This intermediate is then reacted with 4-bromo-2-fluoro-N-(2-fluoro-5-methoxyphenyl)benzenesulfonamide to yield binimetinib [1]. The process emphasizes the stereoselective synthesis of the chiral intermediate, ensuring the correct enantiomer of binimetinib is produced [1].
What are the key intermediates in binimetinib synthesis?
Key intermediates identified in the synthesis process include compounds that facilitate the stepwise assembly of the binimetinib molecule. The patent specifically mentions (S)-N-(3-amino-1-hydroxypropyl)-2-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxamide as a crucial intermediate [1].
What is the therapeutic use of binimetinib?
Binimetinib is a selective inhibitor of MEK1 and MEK2 enzymes [2]. It is used in combination with encorafenib to treat certain types of melanoma with BRAF mutations [2].
What is the patent status of binimetinib synthesis?
WO 2003 077914 A1 is a published patent application, indicating a potential patent filing related to the synthesis of binimetinib [1]. Patents protect the inventive aspects of a synthesis process, granting exclusive rights to the patent holder for a specific period.
Who developed the synthesis process described in WO 2003 077914 A1?
The inventors listed on the patent application WO 2003 077914 A1 are associated with Array BioPharma, Inc. [1]. Array BioPharma, Inc. is the company that developed binimetinib, which was later acquired by Pfizer [3].
What are other methods for synthesizing binimetinib?
While WO 2003 077914 A1 describes a specific synthetic route, other chemical processes may exist or have been developed for binimetinib synthesis. These could involve different starting materials, reagents, or reaction conditions aimed at improving yield, purity, or cost-effectiveness.
How does binimetinib work as a MEK inhibitor?
Binimetinib inhibits MEK1 and MEK2, which are kinases downstream of BRAF in the mitogen-activated protein kinase (MAPK) signaling pathway [2]. This pathway is often dysregulated in cancers with BRAF mutations, and inhibiting MEK can help to block tumor cell proliferation and survival [2].
What are the risks associated with binimetinib treatment?
Common side effects of binimetinib, when used in combination with encorafenib, can include diarrhea, nausea, vomiting, fatigue, and skin-related issues [2]. More serious risks can also occur [2].
How does binimetinib compare to other MEK inhibitors?
Other MEK inhibitors, such as trametinib and cobimetinib, are also used in cancer therapy, often in combination with BRAF inhibitors [4]. The choice of MEK inhibitor may depend on the specific cancer type, genetic mutations present, and physician preference, with differences in efficacy, side effect profiles, and dosing schedules [4].
What is the commercial availability of binimetinib?
Binimetinib is available by prescription, typically marketed under brand names such as Braftovi (encorafenib) in combination with Mektovi (binimetinib) [2].
Sources:
[1] WO 2003 077914 A1 - https://patents.google.com/patent/WO2003077914A1/en
[2] U.S. Food & Drug Administration - https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-encorafenib-and-binimetinib-combination-treatment-unresectable-or-metastatic-melanoma-with-braf
[3] Pfizer Inc. - https://www.pfizer.com/news/press-release/press-release-detail/pfizer-completes-acquisition-array-biopharma-advancing-precision
[4] National Cancer Institute - https://www.cancer.gov/about-cancer/treatment/drugs/binimetinib