Tao, Zhi-Fu; Wang, Le; Stewart, Kent D.; Chen, Zehan; Gu, Wendy; Bui, Mai-Ha; Merta, Philip; Zhang, Haiying; Kovar, Peter; Johnson, Eric; Park, Chang; Judge, Russell; Rosenberg, Saul; Sowin, Thomas; Lin, Nan-Horng published the artcile< Structure-based design, synthesis, and biological evaluation of potent and selective macrocyclic checkpoint kinase 1 inhibitors>, COA of Formula: C4H3NOS, the main research area is macrocyclic diarylurea preparation checkpoint kinase inhibitor.
Based on the crystallog. anal. of a urea-checkpoint kinase 1 (Chk1) complex and mol. modeling, a class of macrocyclic Chk1 inhibitors were designed and their biol. activities were evaluated. An efficient synthetic methodol. 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 Ph ring can tolerate a wide variety of substituents. These Chk1 inhibitors exhibited excellent selectivity over a panel of more than 70 kinases. Some compounds, e.g., I, 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 Chk1 inhibitors abrogate the doxorubicin-induced G2 and camptothecin-induced S checkpoint arrests, confirming that their potent biol. activities are mechanism-based through Chk1 inhibition.
Journal of Medicinal Chemistry published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, COA of Formula: C4H3NOS.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica