<正> In view of quantum pharmacology, the structure-activity relationships of different kinds of fused heterocydic sulfonamides with the same mode of action were first investigated using molecular mechanics, qua...<正> In view of quantum pharmacology, the structure-activity relationships of different kinds of fused heterocydic sulfonamides with the same mode of action were first investigated using molecular mechanics, quantum chemistry and discriminatory analysis. It has been found that the process of the interaction of the fused heterocydic sulfonamide with ALS enzyme involves the electropositive region of the sulfonyl bridge chain and the electronegative region of the heterocydic moiety. The herbicidal activity is related to the potency of electric charge translocation of the related regions.展开更多
Rho-associated coiled-coil-containing protein kinase(RoCK)belongs to the serine-threonine family,and RoCK is involved in a variety of biological processes including cell migration,adhesion,proliferation and differenti...Rho-associated coiled-coil-containing protein kinase(RoCK)belongs to the serine-threonine family,and RoCK is involved in a variety of biological processes including cell migration,adhesion,proliferation and differentiation through phosphorylation of different downstream substrates.The aberrant activation of ROCK is associated with the pathological conditions in different systems including various diseases,including cancer,neurological diseases,inflammation,cardiovascular diseases and glaucoma.Therefore,the ROCK inhibitors have potential applicability for treating the aforementioned diseases.Four small molecule ROCK inhibitors have been approved for clinical use:fasudil,ripasudil,netarsudil and belumosudil.In recent years,more small molecule ROCK inhibitors have been identified.This paper reviews the ROCK inhibitors reported in past seven years.We mainly focused on the summarization of the structure-activity relationships,inhibitory efficacy,pharmacological mechanisms and the relevant clinical studies of the reported ROCK inhibitors.Besides the small molecular inhibitors,the peptides and biological extracts which exhibit ROCK inhibitory effects are also included.We also provide suggestions for the future development of the potent ROCK inhibitors.展开更多
基金Project supported by the National Natural Science Foundation of China
文摘<正> In view of quantum pharmacology, the structure-activity relationships of different kinds of fused heterocydic sulfonamides with the same mode of action were first investigated using molecular mechanics, quantum chemistry and discriminatory analysis. It has been found that the process of the interaction of the fused heterocydic sulfonamide with ALS enzyme involves the electropositive region of the sulfonyl bridge chain and the electronegative region of the heterocydic moiety. The herbicidal activity is related to the potency of electric charge translocation of the related regions.
基金supported by the National Natural Science Foundation of China(Nos.82073311 and 81973866)Natural Science Foundation of Sichuan Province(No.2022JDTD0025)Science and Technology Research Project of Sichuan Traditional Chinese Medicine Administration(No.2021ZD016).
文摘Rho-associated coiled-coil-containing protein kinase(RoCK)belongs to the serine-threonine family,and RoCK is involved in a variety of biological processes including cell migration,adhesion,proliferation and differentiation through phosphorylation of different downstream substrates.The aberrant activation of ROCK is associated with the pathological conditions in different systems including various diseases,including cancer,neurological diseases,inflammation,cardiovascular diseases and glaucoma.Therefore,the ROCK inhibitors have potential applicability for treating the aforementioned diseases.Four small molecule ROCK inhibitors have been approved for clinical use:fasudil,ripasudil,netarsudil and belumosudil.In recent years,more small molecule ROCK inhibitors have been identified.This paper reviews the ROCK inhibitors reported in past seven years.We mainly focused on the summarization of the structure-activity relationships,inhibitory efficacy,pharmacological mechanisms and the relevant clinical studies of the reported ROCK inhibitors.Besides the small molecular inhibitors,the peptides and biological extracts which exhibit ROCK inhibitory effects are also included.We also provide suggestions for the future development of the potent ROCK inhibitors.
