Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors
Neratinib is an oral pan HER inhibitor, that irreversibly inhibits EGFR and HER2 and was proven to be effective against multiple EGFR mutations. In previous study, we reported spiro [indoline-3, 4′-piperidine]-2-ones as anticancer agents. In this study, we designed aminopyridine-containing spiro [in...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2019.1634704 |
| _version_ | 1819076992125894656 |
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| author | Lianbao Ye Tao Zhao Wenjun Du Anhu Li Wei Gao Jingrong Li Ling Wang Weiqiang Chen |
| author_facet | Lianbao Ye Tao Zhao Wenjun Du Anhu Li Wei Gao Jingrong Li Ling Wang Weiqiang Chen |
| author_sort | Lianbao Ye |
| collection | DOAJ |
| description | Neratinib is an oral pan HER inhibitor, that irreversibly inhibits EGFR and HER2 and was proven to be effective against multiple EGFR mutations. In previous study, we reported spiro [indoline-3, 4′-piperidine]-2-ones as anticancer agents. In this study, we designed aminopyridine-containing spiro [indoline-3,4′-piperidine] derivatives A1-A4 using Neratinib and spiro [indoline-3, 4′-piperidine]-2-one compound patented as lead structure, then replaced piperidine with cyclopropane to obtain B1-B7 and replaced indoline with benzmorpholine to get C1-C4 and D1-D2. We synthesized these compounds and evaluated their residual activities under 0.5 M drug concentration on EGFR and ERBB2. Most of compounds showed stronger inhibition on EGFR-wt and ERBB2, in which A1-A4 showed excellent inhibitory activity with inhibition percentage on EGFR-wt kinase of 7%, 6%, 19%, 27%, respectively and 9%, 5%, 12%, 34% on ERBB2 kinase compared with 2% and 6% of Neratinib. |
| first_indexed | 2024-12-21T18:50:06Z |
| format | Article |
| id | doaj.art-24f7f6140f094cf69ee321516054852f |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-21T18:50:06Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-24f7f6140f094cf69ee321516054852f2022-12-21T18:53:47ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-013411233124610.1080/14756366.2019.16347041634704Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitorsLianbao Ye0Tao Zhao1Wenjun Du2Anhu Li3Wei Gao4Jingrong Li5Ling Wang6Weiqiang Chen7Guangdong Pharmaceutical UniversityGuangdong Pharmaceutical UniversityGuangdong Pharmaceutical UniversityEsa Biotech Co., LTD.Guangdong Pharmaceutical UniversityEsa Biotech Co., LTD.South China University of TechnologyGuangdong Pharmaceutical UniversityNeratinib is an oral pan HER inhibitor, that irreversibly inhibits EGFR and HER2 and was proven to be effective against multiple EGFR mutations. In previous study, we reported spiro [indoline-3, 4′-piperidine]-2-ones as anticancer agents. In this study, we designed aminopyridine-containing spiro [indoline-3,4′-piperidine] derivatives A1-A4 using Neratinib and spiro [indoline-3, 4′-piperidine]-2-one compound patented as lead structure, then replaced piperidine with cyclopropane to obtain B1-B7 and replaced indoline with benzmorpholine to get C1-C4 and D1-D2. We synthesized these compounds and evaluated their residual activities under 0.5 M drug concentration on EGFR and ERBB2. Most of compounds showed stronger inhibition on EGFR-wt and ERBB2, in which A1-A4 showed excellent inhibitory activity with inhibition percentage on EGFR-wt kinase of 7%, 6%, 19%, 27%, respectively and 9%, 5%, 12%, 34% on ERBB2 kinase compared with 2% and 6% of Neratinib.http://dx.doi.org/10.1080/14756366.2019.1634704egfr/her2 inhibitorsaminopyridinespiro derivativesegfr mutationsmolecular docking |
| spellingShingle | Lianbao Ye Tao Zhao Wenjun Du Anhu Li Wei Gao Jingrong Li Ling Wang Weiqiang Chen Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry egfr/her2 inhibitors aminopyridine spiro derivatives egfr mutations molecular docking |
| title | Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors |
| title_full | Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors |
| title_fullStr | Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors |
| title_full_unstemmed | Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors |
| title_short | Discovery of aminopyridine-containing spiro derivatives as EGFR mutations inhibitors |
| title_sort | discovery of aminopyridine containing spiro derivatives as egfr mutations inhibitors |
| topic | egfr/her2 inhibitors aminopyridine spiro derivatives egfr mutations molecular docking |
| url | http://dx.doi.org/10.1080/14756366.2019.1634704 |
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