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Both leucovorin and folic acid can be transformed by different enzymes into 5-methyl-tetrahydro-folate, which efficiently crosses the BBB using the folate receptor alpha (FR) transporter, and is thought to be the main active folate in the CNS 99,100

Cells were cultured in the presence of the test compounds for 24 to 48 h at 37C

In sporadic cases, allergic reactions can occur

This trauma extends beyond hair cells, impacting supporting cells essential for cochlear architecture and function, thereby jeopardizing the structural integrity of the auditory system

Following the above general procedure F, A and B respectively and starting from the commercially available 4-chloro-3-nitrobenzoic acid (Scheme 4), the crude reaction mixture was purified by column chromatography (dichloromethane:methanol=40:1) to provide the desired tert-butyl 3-amino-4-(2-adamantylamino)-benzoate (SRS16-82, Scheme 4) (700 mg, 2.046 mmol, 88% (3 steps)

iScience 14 , 210225 (2019)