110506-20-2Relevant academic research and scientific papers
Novel Pyrimidines as Multitarget Protein Tyrosine Kinase Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)
Sun, Bo,Liu, Xiaowen,Zheng, Xu,Wang, Changyuan,Meng, Qiang,Sun, Huijun,Shu, Xiaohong,Liu, Kexin,Sun, Xiuli,Li, Yanxia,Ma, Xiaodong
, p. 182 - 187 (2019/12/03)
A new class of pyrimidine derivatives were identified as potent protein tyrosine kinase (PTK) inhibitors for the treatment of idiopathic pulmonary fibrosis (IPF). Most of these small-molecule inhibitors displayed strong enzymatic activity against BTK and JAK3 kinases at concentrations lower than 10 nM. The representative compound N-(3-((5-chloro-2-(4-((1-morpholino)acetylamino)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (6 a) also exhibited high inhibitory potency toward both BTK and JAK kinase families, as well as ErbB4, at a concentration of 10 nM, achieving rates of inhibition higher than 57 %. Additionally, in vivo biological evaluations showed that 6 a can remarkably decrease the severity of IPF disease. All these investigations suggested that the multi-PTK inhibitor 6 a may serve as a promising agent for the treatment of IPF.
Design and synthesis of diphenylpyrimidine derivatives (DPPYs) as potential dual EGFR T790M and FAK inhibitors against a diverse range of cancer cell lines
Ai, Min,Wang, Changyuan,Tang, Zeyao,Liu, Kexin,Sun, Xiuli,Ma, Tengyue,Li, Yanxia,Ma, Xiaodong,Li, Lei,Chen, Lixue
, (2019/11/26)
A new class of pyrimidine derivatives were designed and synthesized as potential dual FAK and EGFRT790M inhibitors using a fragment-based drug design strategy. This effort led to the identification of the two most active inhibitors, namely 9a and 9f, against both FAK (IC50 = 1.03 and 3.05 nM, respectively) and EGFRT790M (IC50 = 3.89 and 7.13 nM, respectively) kinase activity. Moreover, most of these compounds also exhibited strong antiproliferative activity against the three evaluated FAK-overexpressing pancreatic cancer (PC) cells (AsPC-1, BxPC-3, Panc-1) and two drug-resistant cancer cell lines (breast cancer MCF-7/adr cells and lung cancer H1975 cells) at concentrations lower than 6.936 μM. In addition, 9a was also effective in the in vivo assessment conducted in a FAK-driven human AsPC-1 cell xenograft mouse model. Overall, this study offers a new insight into the treatment of hard to treat cancers.
Synthesis, structure-activity relationship and biological activity of acridine derivatives as potent mdr-reversing agents
Wang, Jianhong,Luo, Tianwei,Li, Shaobin,Zhhang, Yahong,Wang, Chaojie,Zhao, Jin
, p. 4070 - 4079 (2013/12/04)
Multidrug resistance (MDR) mediated by P-glycoprotein is one of the best characterized transporter-mediated barriers to successful cancer chemotherapy. In an attempt to find MDR-reversing agents, a series of novel acridine derivatives were synthesized and evaluated for their in vitro antiproliferative activities against K562 and K562/ADM cells. Some of these compounds showed superior MDR-reversing activities than Amsacrine, the reference compound. Structureactivity relationships (SAR) of these compounds indicated that the N, N-diethylamine moiety had an affect on the in vitro antiproliferative activity. Interestingly, the compounds bearing N, N-diethylamine moiety showed higher growthinhibitory activity against K562/ADM cells than K562 cells. The high duplex DNA binding affinity and inhibition of topoisomerase of these acridine compounds are maintained which were confirmed by fluorescent quenching and DNA topoisomerase II cleavage assay, respectively. Moreover, several compounds were examined for their ability to increase the accumulation of rhodamine 123 in K562 and K562/ADM cells, and the result suggested that they may be inhibitors for P-glycoprotein. Our study suggested that acridine framework is a potentially interesting scaffold for developing novel MDR-reversing agents.
Synthesis of Some New 3-Methoxy-4-acylaminophenylisothiocyanates, 4'-Isothiocyanatophenoxyacetamides/Isobutyramides as Possible Anthelmintic Agents
Shridhar, D. R.,Rao, K. Srinivasa,Singh, A. N.,Rastogi, K.,Jain, M. L.
, p. 1277 - 1280 (2007/10/02)
A number of new 3-methoxy-4-acylaminophenylisothiocyanates (II and III), 4'-isothiocyanatophenoxyacetamides (IV) and 4-isothiocyanatophenoxyisobutyramides (V) have been synthesized and tested for anthelmintic, antiamoebic and antitrichomonal activities.
