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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)

FASEB J 17(1):6769

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

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

Davidson et al., 1977