1628184-28-0Relevant articles and documents
Design, Synthesis, and Biological Evaluation of Imidazopyridines as PD-1/PD-L1 Antagonists
Butera, Roberto,Wa?yńska, Marta,Magiera-Mularz, Katarzyna,Plewka, Jacek,Musielak, Bogdan,Surmiak, Ewa,Sala, Dominik,Kitel, Radoslaw,De Bruyn, Marco,Nijman, Hans W.,Elsinga, Philip H.,Holak, Tad A.,D?mling, Alexander
supporting information, p. 768 - 773 (2021/05/31)
The PD-1/PD-L1 axis has proven to be a highly efficacious target for cancer immune checkpoint therapy with several approved antibodies. Also, small molecules based on a biphenyl core can antagonize PD-1/PD-L1, leading to the in vitro formation of PD-L1 dimers. However, their development remains challenging, as we do not yet fully understand their mode of action. In this work, we designed a new scaffold based on our previously solved high-resolution structures of low-molecular-weight inhibitors bound to PD-L1. A small compound library was synthesized using the Groebke-Blackburn-Bienaymé multicomponent reaction (GBB-3CR), resulting in the structure-activity relationship of imidazo[1,2-a]pyridine-based inhibitors. These inhibitors were tested for their biological activity using various biophysical assays giving potent candidates with low-micromolar PD-L1 affinities. An obtained PD-L1 cocrystal structure reveals the binding to PD-L1. Our results open the door to an interesting bioactive scaffold that could lead to a new class of PD-L1 antagonists.
2-AMINOPYRIMIDIN-6-ONES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
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Paragraph 0183, (2014/09/29)
Described are compounds of Formula I which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-IR), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c- FMS, c-KIT, or PDGFR kinases.
IMIDAZOLIDINONES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
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Paragraph 0309, (2014/10/29)
Described are compounds of Formula I which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-1R), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c-FMS, c-KIT, or PDGFR kinases.
