Wu, Chun-Feng published the artcileSynthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer, HPLC of Formula: 39546-32-2, the publication is European Journal of Medicinal Chemistry (2022), 114055, database is CAplus and MEDLINE.
The development of inhibitors targeting the PI3K-Akt-mTOR signaling pathway has been greatly hindered by the on-target AEs, such as hyperglycemia and hepatotoxicities. In this study, a series of diaryl urea derivatives has been designed and synthesized based on clin. candidate gedatolisib, and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, resp. The terminal L-proline amide substituted derivative I showed 8.6-fold more potent PI3Kα inhibitory activity (0.7 nM) and 4.6-fold more potent antiproliferative effect against HCT116 cell lines (0.11μM) compared with control gedatolisib. The potential antitumor mechanism and efficacy of I in HCT116 xenograft models have also been evaluated, and found I showed comparable in vivo antitumor activity with gedatolisib. The safety investigations revealed that compound I exhibited more safer profiles in the selectivity of liver cells (selectivity index: >6.6 vs 1.85) and blood glucose regulation than gedatolisib. In addition, the in vitro stability assays also indicated that developed compound I possessed good metabolic stabilities.
European Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C9H9BO2, HPLC of Formula: 39546-32-2.
Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem