The invention disclosed a kind of Smad3 protein degraders, their preparation method and application. The claimed compound is shown in structure I (W = CRR’ or C=O; R,R’ = H, D, halo, alkyl, etc.; L = NR”; R” = H, C1-6 alkyl, haloalkyl; X1 = CRx1 or N; X2 = CRx2 or N; X3 = CRx3 or N; X4 = CRx4 or N; X5 = CRx5 or N; Rx1,Rx2,Rx3,Rx4,Rx5 = H, D, halo, alkyl, etc.; Y1 = CRy1or N; Y2 = O, S, or NRy2; Ry1= H,D, halo, alkyl, etc.; Ry2 = H, alkyl, haloalkyl; R1,R2 = H, D, halo, alkyl, haloalkyl, etc.; L1 = CR1R1‘; L2 = O, S, NR2”, or CR2R2‘; L3 = O, S, NR3” or CR3R3‘; L4 = O, S, NR4” or CR4R4‘; L5 = O, S, NR5” or CR5R5‘; L6 = O, S, NR6” or CR6R6‘; L7 = O, S, NR7” or CR7R7‘; R1,R1‘-R7R7‘ = H, D, halo, alkyl, etc.; R2”-R7” = H, C1-6 alkyl or haloalkyl; Ra = D, halo, alkyl, or haloalkyl; n = 0-4 integers). The claimed compound is prepared via multiple steps (procedure given). Theprepd. compound can be used as Smad3 protein degraders for treating Smad3 protein mediated diseases such as autoimmune diseases, inflammation, tissue fibrosis and tumors, etc.
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