The author of 《Structure overhaul affords a potent purine PI3Kδ inhibitor with improved tolerability》 were Methot, Joey L.; Zhou, Hua; Kattar, Sam D.; McGowan, Meredeth A.; Wilson, Kevin; Garcia, Yudith; Deng, Yongi; Altman, Michael; Fradera, Xavier; Lesburg, Charles; Fischmann, Thierry; Li, Chaomin; Alves, Steve; Shah, Sanjiv; Fernandez, Rafael; Goldenblatt, Peter; Hill, Armetta; Shaffer, Lynsey; Chen, Dapeng; Tong, Vince; McLeod, Robbie L.; Yu, Hongshi; Bass, Alan; Kemper, Ray; Gatto, Nicholas T.; LaFranco-Scheuch, Lisa; Trotter, Benjamin Wesley; Guzi, Timothy; Katz, Jason D.. And the article was published in Journal of Medicinal Chemistry in 2019. Product Details of 87120-72-7 The author mentioned the following in the article:
PI3Kδ catalytic activity is required for immune cell activation, and has been implicated in inflammatory diseases as well as hematol. malignancies in which the AKT pathway is overactive. A purine PI3Kδ inhibitor bearing a benzimidazolone-piperidine motif was found to be poorly tolerated in dog, which was attributed to diffuse vascular injury. Several strategies were implemented to mitigate this finding, including reconstruction of the benzimidazolone-piperidine selectivity motif. Structure-based design led to the identification of O- and N-linked heterocycloalkyls, with pyrrolidines being particularly ligand efficient and kinome selective, and having an improved safety pharmacol. profile. A representative was advanced into a dog tolerability study where it was found to be well tolerated, with no histopathol. evidence of vascular injury. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Product Details of 87120-72-7)
tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Large quantities of aliphatic amines are made synthetically. The most widely used industrial method is the reaction of alcohols with ammonia at a high temperature, catalyzed by metals or metal oxide catalysts (e.g., nickel or copper). Mixtures of primary, secondary, and tertiary amines are thereby produced.Product Details of 87120-72-7
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem