The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, 2927-71-1, formula is C4HCl2FN2, Name is 2,4-Dichloro-5-fluoropyrimidine. including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. SDS of cas: 2927-71-1.
Bronner, Sarah M.;Merrick, Karl A.;Murray, Jeremy;Salphati, Laurent;Moffat, John G.;Pang, Jodie;Sneeringer, Christopher J.;Dompe, Nicholas;Cyr, Patrick;Purkey, Hans;Boenig, Gladys de Leon;Li, Jun;Kolesnikov, Aleksandr;Larouche-Gauthier, Robin;Lai, Kwong Wah;Shen, Xiaoli;Aubert-Nicol, Samuel;Chen, Yi-Chen;Cheong, Jonathan;Crawford, James J.;Hafner, Marc;Haghshenas, Pouyan;Jakalian, Araz;Leclerc, Jean-Philippe;Lim, Ngiap-Kie;O’Brien, Tom;Plise, Emile G.;Shalan, Hadil;Sturino, Claudio;Wai, John;Xiao, Yang;Yin, Jianping;Zhao, Liang;Gould, Stephen;Olivero, Alan;Heffron, Timothy P. research published 《 Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma》, the research content is summarized as follows. CDK4 and CDK6 are kinases with similar sequences that regulate cell cycle progression and are validated targets in the treatment of cancer. Glioblastoma is characterized by a high frequency of CDKN2A/CCND2/CDK4/CDK6 pathway dysregulation, making dual inhibition of CDK4 and CDK6 an attractive therapeutic approach for this disease. Abemaciclib, ribociclib, and palbociclib are approved CDK4/6 inhibitors for the treatment of HR+/HER2- breast cancer, but these drugs are not expected to show strong activity in brain tumors due to poor blood brain barrier penetration. Herein, we report the identification of a brain-penetrant CDK4/6 inhibitor derived from a literature mol. with low mol. weight and topol. polar surface area (MW = 285 and TPSA = 66 Å2), but lacking the CDK2/1 selectivity profile due to the absence of a basic amine. Removal of a hydrogen bond donor via cyclization of the pyrazole allowed for the introduction of basic and semi-basic amines, while maintaining in many cases efflux ratios reasonable for a CNS program. Ultimately, a basic spiroazetidine (cpKa = 8.8) was identified that afforded acceptable selectivity over anti-target CDK1 while maintaining brain-penetration in vivo (mouse Kp,uu = 0.20-0.59). To probe the potency and selectivity, our lead compound was evaluated in a panel of glioblastoma cell lines. Potency comparable to abemaciclib was observed in Rb-wild type lines U87MG, DBTRG-05MG, A172, and T98G, while Rb-deficient cell lines SF539 and M059J exhibited a lack of sensitivity.
SDS of cas: 2927-71-1, 2,4-Dichloro-5-fluoropyrimidine is a useful research compound. Its molecular formula is C4HCl2FN2 and its molecular weight is 166.97 g/mol. The purity is usually 95%.
2,4-Dichloro-5-fluoropyrimidine is an aromatic hydrocarbon that has been shown to inhibit the growth of mouse tumor cells in vitro. It also inhibits the production of amines by reacting with industrial chemicals and sodium carbonate. This compound has potent inhibitory activity against autoimmune diseases and cytotoxic potency on mcf-7 cells. Furthermore, 2,4-Dichloro-5-fluoropyrimidine has been shown to have a chlorinating effect on cancer cells., 2927-71-1.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia