COA of Formula: C4H2Cl2N2In 2019 ,《Discovery of a new class of valosine containing protein (VCP/P97) inhibitors for the treatment of non-small cell lung cancer》 appeared in Bioorganic & Medicinal Chemistry. The author of the article were Wang, Xueyuan; Bai, Enhe; Zhou, Hui; Sha, Sijia; Miao, Hang; Qin, Yanru; Liu, Zhaogang; Wang, Jia; Zhang, Haoyang; Lei, Meng; Liu, Jia; Hai, Ou; Zhu, Yongqiang. The article conveys some information:
Valosine containing protein (VCP/p97) is a member of the AAA ATPase family involved in several essential cellular functions and plays an important role in the ubiquitin-mediated degradation of misfolded proteins. P97 has a significant role in maintaining the cellular protein homeostasis for tumor cell growth and survival and has been found overexpressed in many tumor types. No new mol. entities based on p97 target were approved in clinic. Herein, a series of novel pyrimidine structures as p97 inhibitors were designed and synthesized. After enzymic evaluations, structure-activity relationships (SAR) were discussed in detailed. Among the screened compounds, derivative 35 showed excellent enzymic inhibitory activity (IC50, 36 nM). The cellular inhibition results showed that compound 35 had good antiproliferative activity against the non-small cell lung cancer A549 cells (IC50, 1.61 μM). Liver microsome stability showed that the half-life of compound 35 in human liver microsome was 42.3 min, which was more stable than the control CB-5083 (25.8 min). The in vivo pharmacokinetic results showed that the elimination phase half-lives of compound 35 were 4.57 h for ig and 3.64 h for iv, resp. and the oral bioavailability was only 4.5%. These results indicated that compound 35 could be effective for i.v. treatment of non-small cell lung cancer. In the experiment, the researchers used many compounds, for example, 2,4-Dichloropyrimidine(cas: 3934-20-1COA of Formula: C4H2Cl2N2)
2,4-Dichloropyrimidine(cas: 3934-20-1) 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.COA of Formula: C4H2Cl2N2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia