Hit to lead studies on (hetero)arylpyrimidines—Agonists of the canonical Wnt-β-catenin cellular messaging system

Cartilage development and degeneration: a Wnt Wnt situation

“…118 Conversely, (hetero)arylpyrimidines have been identified as agonists of Wnt, and this warrants their investigation, along with other Wnt agonists such as R-spondin2, as therapeutic targets. 134 R-spondin2 and Dkk2 display decreased and increased expression respectively in response to the increased TGF-b observed in OA. Both these molecules contribute to the pathological changes observed in OA cartilage and, as such, warrant the future investigation of neutralizing TGF-b activity in OA.…”

“…Conversely, (hetero)arylpyrimidines have been identified as agonists of Wnt, and this warrants their investigation, along with other Wnt agonists such as R‐spondin2, as therapeutic targets . R‐spondin2 and Dkk2 display decreased and increased expression respectively in response to the increased TGF‐ β observed in OA.…”

Wnt signaling activation: targets and therapeutic opportunities for stem cell therapy and regenerative medicine

“…Gilbert et al reported that (hetero)arylpyrimidines were GSK-3β inhibitors with osteogenic activity in an animal model. 111 Other natural products from plants have also been identified to inhibit GSK-3β, such as andrographolide, from Andrographis paniculata , 112 Euonymus fortunei , Amygdalus communis , Flavone fukugetin , and Garcinia xanthochymus . 113…”

Recent Advances in Direct C–H Functionalization of Pyrimidines

“…100 A wide range of 2-amino-substituted 4-(hetero)arylpyrimidines were obtained from 2-chloropyrimidine (23a) and organolithium compounds 55 by a multistep reaction sequence (Scheme 31). 98,[100][101][102][103][104] Compounds 57 are agonists of the Wnt-b-catenin cellular messaging system, 102,103 while their structural analogues 58 exhibit properties of the serotonin 5-HT receptor ligands. 98,104 For a better understanding of the use of organolithium compounds in the nucleophilic…”