FIGURE 4.
Low molecular weight inhibitors of factor B. (A) Iptacopan (12) was developed from a fragment‐like high‐throughput screening hit (11), by optimizing interactions in the S1 and in the extended S3 pocket. 9 , 105 (B) Crystal structure of the complex between human factor B (green) and iptacopan (magenta, PDB code 6RAV). The indole moiety is binding into the S1 pocket and the piperidine core into the S3 pocket; Shown are key hydrogen bonds to Thr190 and Gly216, respectively. (C) Representative examples of factor B inhibitors with different structural motifs compared to iptacopan extracted from Novartis patents: (13), 112 (14) 113 and (15) 114