294648-35-4

Upstream product

• 203436-46-8 Biphenyl-4-ylmethyl-(2-chloro-9H-purin-6-yl)-amine 
• 75-30-9 2-iodo-propane 
• 712-76-5 N-(4-phenyl)benzylamine 
• 203436-45-7 2,6-dichloro-9-isopropyl-9H-purine 
• 5451-40-1 2,6 dichloropurine 

Downstream Products

• 294647-05-5 (R)-2-(1-hydroxy-but-2-ylamino)-6-[4-(phenyl)phenylmethylamino]-9-iso-propylpurine 
• 441055-91-0 C₂₇H₃₁N₇O 
• 441055-95-4 C₂₇H₃₃N₇ 
• 294647-29-3 C₂₇H₃₃N₇ 
• 294647-33-9 C₂₇H₃₂N₆O 
• 441055-89-6 C₂₅H₂₉N₇ 
• 441055-80-7 C₂₃H₂₇N₇ 
• 441055-84-1 C₂₄H₂₉N₇ 
• 441055-86-3 C₂₅H₃₁N₇ 
• 294648-89-8 C₂₉H₃₇N₇O₂ 
• 441055-93-2 C₃₅H₃₉N₇O₂ 

Relevant academic research and scientific papers

CALCIUM CHANNEL AGONISTS

Embodiments of calcium channel agonists, as well as methods of making and using the calcium channel agonists, are disclosed. The disclosed calcium channel agonists and corresponding salt forms have a structure according to general formula I wherein each bond depicted as " " is a single bond or a double bond as needed to satisfy valence requirements; Z1, Z2, Z3, Z4, and Z5 independently are nitrogen or carbon; R1 and R3 are alkyl; R2 is alkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl; and R4 is alkyl or hydroxyalkyl.

Synthesis and biological evaluation of a selective N- and P/Q-Type calcium channel agonist

The acute effect of the potent cyclin-dependent kinase (cdk) inhibitor (R)-roscovitine on Ca2+ channels inspired the development of structural analogues as a potential treatment for motor nerve terminal dysfunction. On the basis of a versatile chlorinated purine scaffold, we have synthesized ca. 20 derivatives and characterized their N-type Ca2+ channel agonist action. 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.

Biaryl purine derivatives as potent antiproliferative agents: Inhibitors of cyclin dependent kinases. Part I

The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino group of the Cdk inhibitor roscovitine (2), maintained the potent Cdk inhibition demonstrated by roscovitine (2) as well as greatly improving the antiproliferative activity. A series of C-6 biarylmethylamino derivatives was prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions to provide compounds that displayed potent cytotoxic activity against tumor cell lines. In particular, derivative 21h demonstrated a >750-fold improvement in the growth inhibition of HeLa cells compared to roscovitine (2).

Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1

Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-β peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC 50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1δ provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of amyloid-β in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.

Synthesis and activity of 2,6,9-trisubstituted purines

The preparation of a series of 2,6,9-trisubstituted purines and the structure-activity data for the inhibition of cyclin dependent kinase, CDK2 are presented.