Bertrand, Jeanluc; Dostalova, Hana; Krystof, Vladimir; Jorda, Radek; Castro, Alejandro; Mella, Jaime; Espinosa-Bustos, Christian; Maria Zarate, Ana; Salas, Cristian O. published the article 《New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia》. Keywords: purine preparation SAR antileukemic activity cytotoxicity; Bcr-Abl inhibitors; Btk inhibitors; Docking; Leukemia; Purine derivatives; QSAR.They researched the compound: 2,6-Dichloropurine( cas:5451-40-1 ).Application In Synthesis of 2,6-Dichloropurine. Aromatic heterocyclic compounds can be divided into two categories: single heterocyclic and fused heterocyclic. In addition, there is a lot of other information about this compound (cas:5451-40-1) here.
Bcr-Abl and Btk kinases are among the targets that have been considered for the treatment of leukemia. Therefore, several strategies have focused on the use of inhibitors as chemotherapeutic tools to treat these types of leukemia, such as imatinib (for Bcr-Abl) or ibrutinib (for Btk). However, the efficacy of these drugs has been reduced due to resistance mechanisms, which have motivated the development of new and more effective compounds In this study, 2,6,9-trisubstituted purine derivatives I (R = C6H5, 3-FC6H4, 4-CH3OC6H4, etc.; R1 = H, F) were designed, synthesized and evaluated as novel Bcr-Abl and Btk inhibitors. The compounds I (R = 3-FC6H4; R1 = H) and (R = 3,4-(F)2C6H3; R1 = H) were identified as potent inhibitors of both kinases (IC50 values of 40 nM and 0.58/0.66μM for Abl and Btk, resp.). From docking and QSAR analyses, it was concluded that fluorination of the arylpiperazine system is detrimental to the activity against two kinases, and also validated the hypothesis that the substitution on the 6-phenylamino ring is important for the inhibition of both kinases. In addition, the studies indicated that most compounds could suppress the proliferation of leukemia and lymphoma cells (HL60, MV4-11, CEM, K562 and Ramos cells) at low micromolar concentrations in vitro. Finally, the compound I (R = 3-FC6H4; R1 = H) inhibited the downstream signaling of both kinases in the resp. cell models. Therefore, I (R = 3-FC6H4; R1 = H) and (R = 3,4-(F)2C6H3; R1 = H) possessed potency to be further optimized as anti-leukemia drugs by simultaneously inhibiting the Bcr-Abl and Btk kinases.
There is still a lot of research devoted to this compound(SMILES：C2=NC1=C(C(=NC(=N1)Cl)Cl)[NH]2)Application In Synthesis of 2,6-Dichloropurine, and with the development of science, more effects of this compound(5451-40-1) can be discovered.
Reference:
Oxazolidine – Wikipedia,
Oxazolidine | C3H7NO – PubChem