Fused cyanopyridine compound and preparation method and application thereof

Abstract

The invention discloses a fused cyanopyridine compound shown as a general formula I-1 or I-2, or a pharmaceutically acceptable salt thereof, or an enantiomer, a diastereoisomer, a tautomer, a torsional isomer, a solvate, a polymorphic substance or a prodrug thereof, and a preparation method and a pharmaceutical application of the fused cyanopyridine compound, wherein the definition of each group is shown in the specification.

Description

Technical field[0001]The invention belongs to the field of medicinal chemistry, and specifically relates to a class of condensed cyanopyridine compounds, compounds with the activity of inhibiting Ras mutein, preparation methods and uses.Background technique[0002]Ras was the first oncogene identified in human tumors, and was first discovered in two murine sarcoma viruses. The RAS gene family has three members, namely H-Ras, K-Ras, and N-Ras. In human tumors, K-Ras mutations are the most common, accounting for about 85%. Previous studies have shown that the K-Ras mutation can cause cancer because of a missense mutation in codon 12, which changes the structure of the K-Ras protein and keeps it in an active state. The role of Ras in signal pathway transmission is mainly to activate kinases that control gene transcription, thereby regulating cell differentiation and proliferation, and is closely related to tumor cell survival, proliferation, migration, metastasis and angiogenesis. Accord...

AI Technical Summary

Problems solved by technology

However, more than 30 years have passed since the K-Ras oncogene was first discovered, and several generations of targeted drugs for common proto-oncogenes such as EGFR and BCL have gone through, but the targeted drug for K-Ras has not been successfully developed yet.

For a long time, targeted drugs against K-Ras pathway mutant tumors have mainly focused on farnesyl transferase inhibitors and Raf-MEK pathway inhibitors, but with little success

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