K2CO3 Promoted Cascade Reaction for the Preparation of 1H-Imidazol-4- yl-1-amine Derivatives

Abstract

: A K2CO3 promoted efficient one pot two-step method for the preparation of 1H-imidazol-4- yl-1-amine derivatives has been developed. A series of second amines with an imidazole group were obtained with 56%-91% yields by the K2CO3 promoted amination of acetates and nitrogen deprotection of the imidazole process.

Discovery of an Exceptionally Orally Bioavailable and Potent HPK1 PROTAC with Enhancement of Antitumor Efficacy of Anti-PD-L1 Therapy

“…We selected 30 HPK1 inhibitors from literature and patents and assessed their affinity with HPK1 using MM/GBSA and Glids software (Figure S3 and Table S1). ,,,− The correlation between MM/GBSA and Glids scores (Figure A) guided the selection of the top 10 inhibitors, which were then combined with the “linker + CRBN ligand” segment of SS47 , a HPK1 PROTAC that has been comprehensively evaluated to enhance tumor immunity, to create PROTACs P1–P10 (Figures S4 and S5). Predictions of the physicochemical properties of these assembled PROTACs using the ADMETlab 2.0 Web site (Table S2) indicated that PROTAC P10 exhibited more favorable characteristics (MW = 929.4, nRig = 49, nRing = 8, nRot = 22, TPSA = 211.89, nHD = 2) for oral absorption (Figure B).…”