Prodrugs for colon-restricted delivery: Design, synthesis, and in vivo evaluation of colony stimulating factor 1 receptor (CSF1R) inhibitors
Fig 19
Synthesis of ester, glucoside and glucuronide prodrugs.
Reagents and conditions: (a) 2-(dimethylamino)acetic acid, EDC, DMAP, DCM, rt, 92%; (b) Boc-(D)-valine, EDC, DMAP, DCM, rt, 72%; (c) TFA, DCM, 0°C to rt, 73% (d) 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl trichloroacetimidate, BF3.OEt2, -78°C to rt, DCM, 95%; (e) Pd/C, H2 (10 bar), rt, 30% 9, 17% 10; (f) (2R,3R,4S,5S,6S)-2-bromo-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate, AgOTf, DCM, 5°C to rt, 7%; (g) LiOH, THF/H2O, 0°C, 50%.