Liang, Mary; Tarr, Tyler B.; Bravo-Altamirano, Karla; Valdomir, Guillermo; Rensch, Gabriel; Swanson, Lauren; DeStefino, Nicholas R.; Mazzarisi, Cara M.; Olszewski, Rachel A.; Wilson, Gabriela Mustata; Meriney, Stephen D.; Wipf, Peter published the artcile< Synthesis and Biological Evaluation of a Selective N- and P/Q-Type Calcium Channel Agonist>, Safety of 2,6-Dichloro-9-methyl-9H-purine, the main research area is diaminopurine preparation calcium channel agonist structure activity; roscovitine analog preparation calcium channel agonist; cyclin dependent kinase inhibitor roscovitine analog; LEMS; Lambert−Eaton myasthenic syndrome; N/P/Q-type calcium channels; cdk2; neurological autoimmune disorder; roscovitine; selective agonist.
The acute effect of the potent cyclin-dependent kinase (cdk) inhibitor (R)-roscovitine on Ca2+ channels inspired the development of structural analogs as a potential treatment for motor nerve terminal dysfunction. On the basis of a versatile chlorinated purine scaffold, we have synthesized ca. 20 derivatives, I [R1 = n-Pr, Me, CHMe2, R2 = CH2Ph, CH(Ph)2, 3-pyridinylmethyl, etc.], and characterized their N-type Ca2+ channel agonist action. I were prepared by reacting 2,6-dichloro-9H-purine with R1X/K2CO3/DMSO (X = halo), followed by reaction with R2NH2/NEt2/BuOH, which gave the 4-chloro-6-amino derivatives; the final step consisted of treating the latter compounds with (R)-2-amino-1-butanol at 170°C. Agents that showed strong agonist effects were also characterized in a kinase panel for their off-target effects. Among several novel compounds with diminished cdk activity, we identified a new lead structure with a 4-fold improved N-type Ca2+ channel agonist effect and a 22-fold decreased cdk2 activity as compared to (R)-roscovitine. This compound was selective for agonist activity on N- and P/Q-type over L-type calcium channels.
ACS Medicinal Chemistry Letters published new progress about Cyclin-dependent kinase inhibitors. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Safety of 2,6-Dichloro-9-methyl-9H-purine.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics