7-site substituted pyrrolotriazine compounds or pharmaceutically available salt thereof, and preparation method and use thereof

Abstract

The present invention relates to 7-site substituted pyrrole [2,1-f][1,2,4] triazine compounds or pharmaceutically acceptable salts thereof, and a preparation method therefor and uses thereof. This kind of compound shows good PI3K inhibition activity, can effectively inhibit the activity of the PI3K kinase; and due to the introduction of 7-site groups, bioavailability and other pharmacokinetic properties have been greatly improved. In addition, the compounds in the present invention show an unpredictable high selectivity and strong inhibitory activity on PI3kdelta, accordingly, the compounds can be used to treat diseases associated with PI3K pathways, especially for resisting against cancers or treatment of tumors, leukemia and autoimmune diseases. After further optimization and screening,the compounds are expected to develop into new antitumor drugs.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to a 7-position substituted pyrrolotriazine compound or a pharmaceutically acceptable salt thereof, as well as a preparation method and use thereof. Background technique [0002] The PI3K-Akt-mTOR signaling pathway is one of the main pathways that transmit signals from receptor tyrosine kinases and G protein-coupled receptors, and plays an important role in a variety of cellular functions. Recent studies have found that in a variety of human tumors, multiple key node proteins in the PI3K-Akt-mTOR signaling pathway are overactivated due to mutations or amplifications in the encoding genes [Vivancod et al., Nat Rev Cancer 2 (2002) , pp. 489-501]. Among them, PI3K, as a bridge molecule linking extracellular signals and cell response effects, is a key factor in regulating cell growth, metabolism and survival, and its overactivation is closely related to the occurrence of vari...

AI Technical Summary

Problems solved by technology

Although this type of compound also has PI3Kδ selectivity reported [Murray et al., J Med Chem 55 (2012), p. 7686-7695], the properties of the core and pyrrolotriazine are quite different

However, there are only a few reports of PI3K inhibitors based on pyrrolotriazine as the mother nucleus, such as CN102675323A, and there is no report on the inhibitory activity of PI3Kδ so far.

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