Fig. 1: A schematic for the comparison of the old method and the 2D-FAST.

A Synthesis of the monopyridyls with various side chains (Ri,j,k) and the number of synthetic steps following the old method. (Inset) The chemical structures of the side chains on OPs. A flowchart for the synthesis of dipyridyls and tripyridyls and their testing against various biological targets. B The 2D-FAST schematic and conditions: a ROH, NaH or Na metal, toluene, 50 min. at 0 °C, then 5 h at r.t. b Screening and identication of the potent antagonist monopyridyls against αS aggregation using ThT aggregation assay. c, g Pd/C, H2 (g), EtOAc, 3 h at r.t. d 6-chloro-5-nitropicolinic acid, DCM (anhydrous), triethylamine, thionyl chloride, 0 °C to r.t., 45 min. e, i Primary amine/thiol, DIPEA, DCM, 3 h at r.t. f Screening and identication of the potent antagonist dipyridyls against αS aggregation using ThT aggregation assay. h 6-chloro-5-nitropicolinoyl chloride, dichloroethane (DCE), saturated sodium bicarbonate (NaHCO3), 10 min at 0 °C. j Screening and identication of the potent antagonist tripyridyls against αS aggregation using ThT aggregation assay. C The representation of two dimensions in the 2D-FAST.