Discovery and SAR studies of novel 2-anilinopyrimidine-based selective inhibitors against triple-negative breast cancer cell line MDA-MB-468

Bioorg Med Chem Lett. 2019 Jan 1;29(1):62-65. doi: 10.1016/j.bmcl.2018.11.010.

Jeyun Jo ¹, Sou Hyun Kim ¹, Heegyu Kim ¹, Myeonggyo Jeong ¹, Jae-Hwan Kwak ², Young Taek Han ³, Jee-Yeong Jeong ⁴, Young-Suk Jung ⁵, Hwayoung Yun ⁶

Affiliations

1 College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
2 College of Pharmacy, Kyungsung University, Busan 48434, Republic of Korea.
3 College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
4 Department of Biochemistry, Kosin University College of Medicine, Busan 49267, Republic of Korea.
5 College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea. Electronic address: youngjung@pusan.ac.kr.
6 College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea. Electronic address: hyun@pusan.ac.kr.

PMID: 30447889 DOI: 10.1016/j.bmcl.2018.11.010

Abstract

Triple-negative breast cancers (TNBCs) are characterized as an invasive and intractable subtype of breast cancers. Overexpression of epidermal growth factor receptor (EGFR) has been considered to be an important target for TNBC therapy, but efficacies of EGFR inhibitors in clinical trials are elusive. In this study, novel series of 2-anilinopyrimidines were synthesized in an effort to identify selective inhibitors against an EGFR-overexpressing TNBC cell line. Biological evaluation demonstrated that compounds 21 and 38, with a 4-methylpiperidine group and a high ClogP value, exhibited good potency and selectivity for the TNBC cell line. This study has provided evidence to support further development of 2-anilinopyrimidine-based TNBC selective inhibitors and investigation of the targets of compounds 21 and 38.

Keywords

2-Anilinopyrimidine; Growth inhibition; Lipophilicity; Selectivity index; Triple-negative breast cancer.

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