Potent inhibitors of CDK5 derived from roscovitine: Synthesis, biological evaluation and molecular modelling was written by Demange, Luc;Abdellah, Fatma Nait;Lozach, Olivier;Ferandin, Yoan;Gresh, Nohad;Meijer, Laurent;Galons, Herve. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2013.Safety of 2,6-Dichloro-9-isopropyl-9H-purine This article mentions the following:
9-Isopropyl-2-(hydroxyalkylamino)-6-(arylamino)purines I [R = 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 4-pyridazinyl; R1 = Cl, (R)-Et(HOCH2)CHNH, (S)-Et(HOCH2)CHNH, (R)-Me2CH(HOCH2)CHNH, (S)-Me2CH(HOCH2)CHNH, (HOCH2)2CH, HOCH2CMe2NH, 5-pyrimidinylamino, 2-pyrazinylamino] were prepared as analogs of the CDK inhibitor roscovitine for potential use as selective inhibitors of cyclin-dependent kinase 5 (CDK5) over CDK2, glycogen synthase kinase-3 (GSK3αβ), and casein kinase 1 (CK1). Regioselective alkylation of 2,6-dichloropurine, regioselective Buchwald-Hartwig amination with arylamines, and reaction with amino alcs. yielded I, with chlorides generated by omission of the reaction with amino alcs., and I (R = R1 = 5-pyrimidinylamino, 2-pyrazinylamino) generated as diamination byproducts from Buchwald-Hartwig amination. I [R = 3-pyridinyl, 4-pyridinyl, 5-pyrimidinyl, 4-pyridazinyl; R1 = (R)-Et(HOCH2)CHNH, (S)-Et(HOCH2)CHNH, (R)-Me2CH(HOCH2)CHNH] inhibited CDK5 with IC50 values ranging from 17 to 50 nM and induced cell death in human neuroblastoma cells with IC50 values ranging from 2 to 9 μM in SH-SY5Y cells. Mol. docking of I [R = 4-pyrimidinyl; R1 = (R)-Et(HOCH2)CHNH] and I [R = 4-pyridazinyl; R1 = (R)-Et(HOCH2)CHNH] into the ATP binding domain of the CDK5 catalytic site highlighted the importance of a hydrogen bond between the arylamino ring nitrogen atoms and residue Lys-89 of CDK5 for enzyme inhibition. The calculated final energy balances for complexation measured for several inhibitors is consistent with the ranking of the IC50 values. I [R = 3-pyridinyl, 5-pyrimidinyl; R1 = (R)-Me2CH(HOCH2)CHNH, (S)-Me2CH(HOCH2)CHNH] inhibited dual specificity, tyrosine phosphorylation regulated kinase 1A (DYRK1A), a kinase involved in Down’s syndrome and Alzheimer’s disease, with IC50 values ranging from 300 to 400 nM. In the experiment, the researchers used many compounds, for example, 2,6-Dichloro-9-isopropyl-9H-purine (cas: 203436-45-7Safety of 2,6-Dichloro-9-isopropyl-9H-purine).
2,6-Dichloro-9-isopropyl-9H-purine (cas: 203436-45-7) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Alkyl chlorides are versatile building blocks in organic chemistry. While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available.Safety of 2,6-Dichloro-9-isopropyl-9H-purine
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics