Category: pyrimidinesIn 2021 ,《Discovery and Synthesis of a Pyrimidine-Based Aurora Kinase Inhibitor to Reduce Levels of MYC Oncoproteins》 appeared in Journal of Medicinal Chemistry. The author of the article were Chi, Ya-Hui; Yeh, Teng-Kuang; Ke, Yi-Yu; Lin, Wen-Hsing; Tsai, Chia-Hua; Wang, Wan-Ping; Chen, Yen-Ting; Su, Yu-Chieh; Wang, Pei-Chen; Chen, Yan-Fu; Wu, Zhong-Wei; Yeh, Jen-Yu; Hung, Ming-Chun; Wu, Mine-Hsine; Wang, Jing-Ya; Chen, Ching-Ping; Song, Jen-Shin; Shih, Chuan; Chen, Chiung-Tong; Chang, Chun-Ping. The article conveys some information:
The design and synthesis of a series of pyrimidine-based derivatives I (R1 = phenylcarbonyl, (3-chloro-2-fluorophenyl)carbonyl, (6-chloro-2-fluoropyridin-3-yl)carbonyl, etc.; R2 = 4-ethylpiperazin-1-yl, 3-(dimethylamino)azetidin-1-yl, (3S)-3-(dimethylamino)pyrrolidin-1-yl, etc.), which able to inhibit Aurora A kinase activity and reduce levels of cMYC and MYCN were described. Through structure-based drug design of a small mol. that induces the DFG-out conformation of Aurora A kinase, lead compound I (R1 = (4-chloro-2-fluorophenyl)carbonyl; R2 = 4-ethylpiperazin-1-yl) was identified, which potently (IC50 <200 nM) inhibited the proliferation of high-MYC expressing small-cell lung cancer (SCLC) cell lines. Pharmacokinetic optimization of I (R1 = (4-chloro-2-fluorophenyl)carbonyl; R2 = 4-ethylpiperazin-1-yl) by prodrug strategies resulted in orally bioavailable II, which demonstrated an 8-fold higher oral AUC (F = 62.3%). Pharmacodynamic studies of II showed it to effectively reduce cMYC protein levels, leading to >80% tumor regression of NCI-H446 SCLC xenograft tumors in mice. These results support the potential of II for the treatment of MYC-amplified cancers including SCLC. The experimental process involved the reaction of 2,4,6-Trichloropyrimidine(cas: 3764-01-0Category: pyrimidines)
2,4,6-Trichloropyrimidine(cas: 3764-01-0) is a member of organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. They are generally not present in crude oils and are typically the result of additives, cleaning solutions or chemicals used for oil recovery.Category: pyrimidines
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia