How is Regorafenib Synthesized?
The synthesis of Regorafenib involves a multi-step process that typically includes the formation of key intermediates. One described synthesis route involves the reaction of 4-chloro-3-(trifluoromethyl)aniline with 4-isocyanatobenzoic acid derivatives [1]. The trifluoromethyl group is often introduced early in the synthetic pathway [2].
What is the Role of Isocyanates and Anilines in Regorafenib Synthesis?
Anilines, such as 4-chloro-3-(trifluoromethyl)aniline, serve as crucial building blocks in the synthesis of Regorafenib, providing a core aromatic structure [1]. Isocyanates, like derivatives of 4-isocyanatobenzoic acid, are reactive functional groups that facilitate the formation of amide linkages, which are integral to the Regorafenib molecule [1].
What Patents Cover Regorafenib Synthesis?
Patents related to Regorafenib synthesis often focus on novel routes, specific intermediates, or improved processes to enhance yield or purity [3]. For example, patents may detail methods for preparing key precursors or the final active pharmaceutical ingredient (API) itself [3][4]. The original patent for Regorafenib was filed by Bayer [5].
When Does Regorafenib's Core Patent Protection Expire?
The primary patent protection for Regorafenib, covering the compound itself and its initial therapeutic uses, has largely expired or is nearing expiration in various regions, paving the way for potential generic competition [5][6]. Specific expiry dates can vary by country and any granted extensions.
Can Generic Regorafenib Enter the Market Before Patent Expiry?
The entry of generic Regorafenib is generally contingent upon the expiration of key patents, including those related to the synthesis of the active ingredient and its approved indications [6]. However, patent litigation and the development of new formulations or manufacturing processes can sometimes affect the timeline for generic market entry [7].
Who are the Key Manufacturers and Competitors in the Regorafenib Market?
Bayer is the originator of Regorafenib, marketed as Stivarga [5]. Following patent expirations, other pharmaceutical companies may seek to develop and market generic versions of Regorafenib, leading to increased competition [6].
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1. Bayer HealthCare AG, European patent EP 2083073 B1 (2012)
2. U.S. Patent 8,394,970 (2013)
3. European patent EP 2955571 A1 (2015)
4. U.S. Patent 9,573,879 B2 (2017)
5. Bayer AG, Original Regorafenib patent filing
6. Generic competition for Stivarga (regorafenib) expected in 2022-2023 in the US
7. FDA guidance on generic drug approval