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ID: ALA4425186

Journal: Bioorg Med Chem Lett

Title: Discovery and SAR of pyrrolo[2,1-f][1,2,4]triazin-4-amines as potent and selective PI3Kδ inhibitors.

Authors: Bhide RS, Neels J, Qin LY, Ruan Z, Stachura S, Weigelt C, Sack JS, Stefanski K, Gu X, Xie JH, Goldstine CB, Skala S, Pedicord DL, Ruepp S, Dhar TG, Carter PH, Salter-Cid LM, Poss MA, Davies P.

Abstract: Aberrant Class I PI3K signaling is a key factor contributing to many immunological disorders and cancers. We have identified 4-amino pyrrolotriazine as a novel chemotype that selectively inhibits PI3Kδ signaling despite not binding to the specificity pocket of PI3Kδ isoform. Structure activity relationship (SAR) led to the identification of compound 30 that demonstrated efficacy in mouse Keyhole Limpet Hemocyanin (KLH) and collagen induced arthritis (CIA) models.

CiteXplore: 27476421

DOI: 10.1016/j.bmcl.2016.07.047