865715-87-3

Upstream product

• 106-95-6 allyl bromide 

Downstream Products

• 865715-88-4 N-(2-(allyloxy)-5-chloro-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)-N'-[6-(but-3-enyloxy)-5-cyanopyrazin-2-yl]urea 
• 865716-76-3 N-(2-(allyloxy)-5-chloro-4-{[2-(trimethylsilyl)ethoxy]methoxy}phenyl)-N'-[3-(but-3-enyloxy)-4-cyanophenyl]urea 
• 1000806-98-3 C₂₄H₃₀ClN₅O₅Si 

Relevant academic research and scientific papers

Synthesis of macrocyclic urea kinase inhibitors

An efficient and convergent route was developed for the synthesis of a novel class of urea-based macrocyclic kinase inhibitors. The synthesis is featured with an efficient urea formation by using a key carbamate intermediate and with a smooth ring-closure olefin metathesis. Furthermore, the hydrogenations of the resulting olefins were investigated in this complex macrocyclic ring system. Georg Thieme Verlag Stuttgart.

Structure-based design, synthesis, and biological evaluation of potent and selective macrocyclic checkpoint kinase 1 inhibitors

Based on the crystallographic analysis of a urea-checkpoint kinase 1 (Chk1) complex and molecular modeling, a class of macrocyclic Chk1 inhibitors were designed and their biological activities were evaluated. An efficient synthetic methodology for macrocyclic ureas was developed with Grubbs metathesis macrocyclization as the key step. The structure-activity relationship studies demonstrated that the macrocyclization retains full Chk1 inhibition activity and that the 4-position of the phenyl ring can tolerate a wide variety of substituents. These novel Chk1 inhibitors exhibit excellent selectivity over a panel of more than 70 kinases. Compounds 5b, 5c, 5f, 15, 16d, 17g, 17h, 17k, 18d, and 22 were identified as ideal Chk1 inhibitors, which showed little or no single-agent activity but significantly potentiate the cytotoxicities of the DNA-damaging antitumor agents doxorubicin and camptothecin. These novel Chk1 inhibitors abrogate the doxorubicin-induced G2 and camptothecin-induced S checkpoint arrests, confirming that their potent biological activities are mechanism-based through Chk1 inhibition.

Macrocyclic kinase inhibitors

Compounds having the formula are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.