Composition for HER2 inhibition containing a heteroaryl derivative as an active ingredient

Quinazoline-based anticancer candidate with a methylquinoline oxyphenyl structure that selectively inhibits HER2 over EGFR

This technology features novel heteroaryl derivative compounds, along with their salts, solvates, and stereoisomers, in which a methyl-substituted quinoline or isoquinoline is linked via oxygen to a phenyl group on a quinazolin-4-amine backbone. These compounds selectively inhibit HER2 tyrosine kinase and are used as agents for the treatment and prevention of HER2-related cancers.

HER2 is amplified in 15–30% of breast cancer patients and is associated with brain metastasis; it is also overexpressed in colorectal, gastric, non-small cell lung, and ovarian cancers. However, most drugs reported to date are dual inhibitors that block both EGFR and HER2. Strong inhibition of EGFR often leads to side effects such as acneiform skin rashes and severe diarrhea, creating a persistent need for selective HER2 inhibitors.

This technology consists of detailed series (Chemical Formulas 1-1 through 1-4) featuring side chains such as 2-methoxyethoxy, morpholinoalkoxy, propargyloxy, or triazole methoxy at the 6th and 7th positions of the quinazoline, or amide/cycloalkylamine groups at the 6th position. In experiments, these derivatives showed higher selectivity for HER2 than EGFR and demonstrated cell proliferation inhibitory effects comparable to the existing drug lapatinib. Applicable to the development of HER2-positive breast cancer targeted therapies, HER2-inhibiting anticancer drugs for gastric and ovarian cancers, and the exploration of health supplement ingredients for cancer prevention, this technology provides HER2-selective candidates that reduce the skin rash and diarrhea side effects caused by EGFR inhibition.

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Key Features:

• Heteroaryl derivative compounds of Formula 1 having a methyl-substituted or unsubstituted quinoline or isoquinoline as Ar
• Heteroaryl derivative compounds having R1 and R2 substituents selected from hydrogen, methyl, methoxy, fluorine, and chlorine
• Quinazoline derivative compounds of Formula 1-2 where R3 is hydrogen or -O-R5 and R4 is hydrogen, methoxy, or 2-methoxyethoxy
• Derivative compounds of Formula 1-4 with a (C5-C6)cycloalkyl or tetrahydropyran amino group bonded at the 6th position of the quinazoline

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This invention was developed with support from the Ministry of Science and ICT for research on platform technology for the discovery of reversible covalent inhibitors.

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