1000894-87-0Relevant articles and documents
Core modification of substituted piperidines as Novel inhibitors of HDM2-p53 protein-protein interaction
Pan, Weidong,Lahue, Brian R.,Ma, Yao,Nair, Latha G.,Shipps Jr., Gerald W.,Wang, Yaolin,Doll, Ronald,Bogen, Stéphane L.
, p. 1983 - 1986 (2014/04/17)
The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency.
