Borofalan (10B): Synthesis and Introduction

Synthesis of Borofalan (10B)

Borofalan (10B) is synthesised using (S)-4-iodophenylalanine as raw material by chemical reaction. The specific synthesis steps are as follows:

Several different routes to the API start from (S)-N-Boc-4- iodophenylalanine (230), which is readily accessible via Boc protection of (S)-4-iodophenylalanine (229). Borylation via metal−halogen exchange and quench with tributyl borate followed by Boc deprotection afforded borofalan (10B).

Introduction of Borofalan (10B)

Borofalan (10B) was developed by Stella Pharma and approved by the Japan PMDA for the treatment of patients with unresectable, locally advanced, or locally recurrent head and neck cancer. The drug alone does not inhibit tumor growth but instead is used with boron neutron capture therapy (BNCT). Upon irradiation of neutron beams from outside the body, 10B atoms incorporated in tumor cells release alpha rays and lithium nuclei with cell-killing effects. In an open-label, uncontrolled Phase 2 study of borofalan (10B)/ BNCT in Japan, the objective response rate (ORR) was 71% with no clear difference between patients with squamous cell carcinoma and nonsquamous cell carcinoma.