In 2022,Goldberg, Frederick W.; Ting, Attilla K. T.; Beattie, David; Lamont, Gillian M.; Fallan, Charlene; Finlay, M. Raymond V.; Williamson, Beth; Schimpl, Marianne; Harmer, Alexander R.; Adeyemi, Oladipupo B.; Nordell, Par; Cronin, Anna S.; Vazquez-Chantada, Mercedes; Barratt, Derek; Ramos-Montoya, Antonio; Cadogan, Elaine B.; Davies, Barry R. published an article in ACS Medicinal Chemistry Letters. The title of the article was 《Optimization of hERG and Pharmacokinetic Properties for Basic Dihydro-8H-purin-8-one Inhibitors of DNA-PK》.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:
Series of neutral DNA-PKcs inhibitors were modified to incorporate a basic group, with the rationale that increasing the volume of distribution while maintaining good metabolic stability should increase the half-life. However, adding a basic group introduced hERG activity and basic compounds with modest hERG activity (IC50 = 10-15μM) prolonged QTc (time from the start of the Q wave to the end of the T wave, corrected by heart rate) in an anesthetized guinea pig cardiovascular model. Further optimization were necessary, including modulation of pKa, to identify I, which combines low hERG activity (IC50 = 75μM) with excellent kinome selectivity and favorable pharmacokinetic properties. In the experiment, the researchers used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate)
tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem