Ten new 1, 5-diarulpyrazole-3-carboxamide compounds were synthesized and their structures were identified by ^1H-NMR and FAB-MS. The primary biological tests showed that compound 4j exhibited some ALK5 inhibitory acti...Ten new 1, 5-diarulpyrazole-3-carboxamide compounds were synthesized and their structures were identified by ^1H-NMR and FAB-MS. The primary biological tests showed that compound 4j exhibited some ALK5 inhibitory activity at concentration of 1μmol/L.展开更多
转化生长因子-β(TGF-β)在许多疾病中过表达,是治疗肿瘤的重要靶点.合成了2个系列3-取代-5-((5-(6-甲基吡啶-2-酰基)-4-(喹啉-6-基)-1氢-咪唑-2-基)亚甲基)-2-噁唑烷-4-酮化合物(12、13a~13e和14a~14h),并对其进行了活性受体样激酶5(AL...转化生长因子-β(TGF-β)在许多疾病中过表达,是治疗肿瘤的重要靶点.合成了2个系列3-取代-5-((5-(6-甲基吡啶-2-酰基)-4-(喹啉-6-基)-1氢-咪唑-2-基)亚甲基)-2-噁唑烷-4-酮化合物(12、13a~13e和14a~14h),并对其进行了活性受体样激酶5(ALK5)抑制活性评价.其中(Z)-6-(5-((5-(6-甲基吡啶-2-基)-4-(喹喔啉-6-基)-1H-咪唑-2-基)亚甲基)-4-羰基-2-硫代羰基噻唑-3-基)己酸(13e)对ALK5激酶的活性最高(IC_(50)=0.451μmol·L^(-1)),对p38α激酶的选择性指数大于22,比临床候选化合物LY-2157299选择性高5.0倍.在TGF-β抑制剂的研究中发现这些罗丹宁化合物具有良好的抗真菌活性,而且对革兰氏阳性菌和革兰氏阴性菌显示很高的选择性.它们显示与阳性对照化合物氟康唑(MIC=1μg/mL)类似或更高的抗真菌活性(MIC=0.5 or 1μg/mL).展开更多
文摘Ten new 1, 5-diarulpyrazole-3-carboxamide compounds were synthesized and their structures were identified by ^1H-NMR and FAB-MS. The primary biological tests showed that compound 4j exhibited some ALK5 inhibitory activity at concentration of 1μmol/L.
基金This work was financially supported by National Natural Science Foundation of China (81600838, 51502262), Key Research and Development Program of Zhejiang, China (2017C01054), Medical Technology and Education of Zhejiang Province of China (2016KYB178), Research Science and Technology Department of Zhejiang Province social welfare development projects under Grant 2013C33161, Natural Science Foundation of Zhejiang Provence of China under Grant LY 15H 160019, and Ningbo Natural Science Foundation 2016A610166.
文摘转化生长因子-β(TGF-β)在许多疾病中过表达,是治疗肿瘤的重要靶点.合成了2个系列3-取代-5-((5-(6-甲基吡啶-2-酰基)-4-(喹啉-6-基)-1氢-咪唑-2-基)亚甲基)-2-噁唑烷-4-酮化合物(12、13a~13e和14a~14h),并对其进行了活性受体样激酶5(ALK5)抑制活性评价.其中(Z)-6-(5-((5-(6-甲基吡啶-2-基)-4-(喹喔啉-6-基)-1H-咪唑-2-基)亚甲基)-4-羰基-2-硫代羰基噻唑-3-基)己酸(13e)对ALK5激酶的活性最高(IC_(50)=0.451μmol·L^(-1)),对p38α激酶的选择性指数大于22,比临床候选化合物LY-2157299选择性高5.0倍.在TGF-β抑制剂的研究中发现这些罗丹宁化合物具有良好的抗真菌活性,而且对革兰氏阳性菌和革兰氏阴性菌显示很高的选择性.它们显示与阳性对照化合物氟康唑(MIC=1μg/mL)类似或更高的抗真菌活性(MIC=0.5 or 1μg/mL).