In the present study,we described a continuous-flow,one-pot synthesis of asymmetrical ureas using nucleophilic addition reaction of amines to isocyanates derived from acids’Curtius rearrangement.The advantages of thi...In the present study,we described a continuous-flow,one-pot synthesis of asymmetrical ureas using nucleophilic addition reaction of amines to isocyanates derived from acids’Curtius rearrangement.The advantages of this method included broad substrate scope,high yields,rapid reaction,simplicity,extraordinary safety,and easy scale-up.展开更多
A continuous-flow synthesis of nitriles by Schmidt reaction has been developed.Using this procedure,a variety of aldehydes could be smoothly transformed into the desired nitriles in good to excellent yields.The mild r...A continuous-flow synthesis of nitriles by Schmidt reaction has been developed.Using this procedure,a variety of aldehydes could be smoothly transformed into the desired nitriles in good to excellent yields.The mild reaction conditions and the flowing reaction system greatly improved the safety and make the reaction easy to scale up.展开更多
Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as nove...Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.展开更多
基金National Natural Science Foundation of China(Grant No.21877005).
文摘In the present study,we described a continuous-flow,one-pot synthesis of asymmetrical ureas using nucleophilic addition reaction of amines to isocyanates derived from acids’Curtius rearrangement.The advantages of this method included broad substrate scope,high yields,rapid reaction,simplicity,extraordinary safety,and easy scale-up.
基金the National Natural Science Foundation of China(No.21877005)for financial support
文摘A continuous-flow synthesis of nitriles by Schmidt reaction has been developed.Using this procedure,a variety of aldehydes could be smoothly transformed into the desired nitriles in good to excellent yields.The mild reaction conditions and the flowing reaction system greatly improved the safety and make the reaction easy to scale up.
基金supported by National Natural Science Foundation of China(Grant Nos.81620108029,81974083,and 81330074)Beijing Natural Science Foundation grant 7172113(China)
文摘Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.
