16230-24-3Relevant academic research and scientific papers
Approaching the active conformation of 1,3-diaminopyrimidine based covalent inhibitors of Bruton's tyrosine kinase for treatment of Rheumatoid arthritis
Huang, Zhenhua,Zhang, Qian,Yan, Lianzhong,Zhong, Guizhen,Zhang, Linqi,Tan, Xiaojuan,Wang, Yanli
, p. 1954 - 1957 (2016)
By applying conformational restrictions, we were able to discover highly potent 1,3-diaminopyrimidine based covalent inhibitors of BTK, such as 8a (IC50 = 3.76 nM), and providing useful information of its active conformation. We are developing these novel small molecule covalent inhibitors of BTK toward oral agents for Rheumatoid arthritis.
Novel amino acid-substituted diphenylpyrimidine derivatives as potent BTK inhibitors against B cell lymphoma cell lines
Wang, Changyuan,Li, Si,Meng, Qiang,Sun, Xiuli,Li, Hua,Shu, Xiaohong,Sun, Huijun,Liu, Kexin,Liu, Zhihao,Ma, Xiaodong
, p. 4179 - 4186 (2018)
A new family of diphenylpyrimidine derivatives bearing an amino acid substituent were identified as potent BTK inhibitors. Among them, compound 7b, which features an L-proline substituent, was identified as the strongest BTK inhibitor, with an IC50/
Discovery of novel quinazoline derivatives as potent PI3Kδ inhibitors with high selectivity
Teng, Yu,Li, Xinyu,Ren, Shengnan,Cheng, Yu,Xi, Kun,Shen, Hongtao,Ma, Wenzhuo,Luo, Guoshun,Xiang, Hua
, (2020)
Inhibition of PI3Kδ has been proved to be an efficacious strategy for the treatment of hematological malignancies where the PI3K/Akt signaling pathway is hyperactive. Herein, a series of quinazoline derivatives bearing acrylamide fragment were prepared using skeleton-deconstruction strategy. The preliminary bioactivity evaluation resulted in the discovery of lead compound 15c. Compound 15c exhibited excellent enzyme activity against PI3Kδ (IC50 = 27.5 nM) compared with BEZ235 as well as the significant anti-proliferation activities. With the high selectivity over other PI3K isoforms and potent effects on PI3K/Akt pathway, 15c can be identified as a promising PI3Kδ inhibitor worthy of further profiling.
Design, synthesis and antitumor activity evaluation of trifluoromethyl-substituted pyrimidine derivatives
Dai, Honglin,Gao, Chao,Ke, Yu,Liu, Hongmin,Liu, Limin,Meng, Yaqi,Si, Xiaojie,Wang, Zhengjie,Zhang, Qiurong,Zhang, Yang,Zheng, Jiaxin
, (2021/09/14)
In order to find efficient new antitumor drugs, a series of novel trifluoromethyl-substituted pyrimidine derivatives were designed and synthesized, and the bioactivity against four human tumor cells (PC-3, MGC-803, MCF-7 and H1975) was evaluated by MTT assay. Compound 17v displayed potent anti-proliferative activity on H1975 (IC50 = 2.27 μΜ), which was better than the positive control 5-FU (IC50 = 9.37 μΜ). Further biological evaluation studies showed that compound 17v induced apoptosis of H1975 cells and arrested the cell cycle at G2/M phase. Furthermore, compound 17v induced H1975 cells apoptosis through increasing the expression of pro-apoptotic proteins Bax and p53 and down-regulating the anti-apoptotic protein Bcl-2. In addition, compound 17v was able to be tightly embedded in the active pocket of EGFR. In summary, these results demonstrated that compound 17v has a potential as a lead compound for further investigation.
Synthesis and biological activity of imidazole group-substituted arylaminopyrimidines (IAAPs) as potent BTK inhibitors against B-cell lymphoma and AML
Li, Si,Wu, Bin,Zheng, Xu,Wang, Changyuan,Zhao, Jingyuan,Sun, Huijun,Sun, Xiuli,Tang, Zeyao,Yuan, Hong,Chen, Lixue,Ma, Xiaodong
, (2020/12/07)
Bruton's tyrosine kinase (BTK) is a member of the Tec kinase family and plays a key role in the modulation of the B-cell receptor (BCR)-mediated signaling pathway. Inhibition of BTK has been proven to be an effective therapeutic approach for various hemat
Design, synthesis and biological evaluation of novel 2,4-disubstituted quinazoline derivatives targeting H1975 cells via EGFR-PI3K signaling pathway
Chao, Gao,Dai, Honglin,Ke, Yu,Li, Erdong,Lihong, Shan,Liu, Hongmin,Liu, Limin,Si, Xiaojie,Wang, Zhengjie,Yang, Zhang,Zhang, Luye,Zhang, Qiurong,Zheng, Jiaxin
, (2021/07/28)
In order to find new and highly effective anti-tumor drugs with targeted therapeutic effects, a series of novel 4-aminoquinazoline derivatives containing N-phenylacetamide structure were designed, synthesized and evaluated for antitumor activity against four human cancer cell lines (H1975, PC-3, MDA-MB-231 and MGC-803) using MTT assay. The results showed that the compound 19e had the most potent antiproliferative activity against H1975, PC-3, MDA-MB-231 and MGC-803 cell lines. At the same time, compound 19e could significantly inhibit the colony formation and migration of H1975 cells. Compound 19e also arrested the H1975 cell cycle in the G1 phase and mediated cell apoptosis, promoted the accumulation of ROS in H1975 cells. Furthermore, compound 19e exerted antitumor effect in vitro by reducing the expression of anti-apoptotic protein Bcl-2 and increasing the pro-apoptotic protein Bax and p53. Mechanistically, compound 19e could significantly decreased the phosphorylation of EGFR and its downstream protein PI3K in H1975 cells. Which indicated that compound 19e targeted H1975 cell via interfering with EGFR-PI3K signaling pathway. Molecular docking showed that compound 19e could bind into the active pocket of EGFR. Those work suggested that compound 19e would have remarkable implications for further design of anti-tumor agents.
S-triazine compounds as well as preparation method and application thereof
-
Paragraph 0069; 0072, (2020/05/05)
The invention discloses s-triazine compounds and pharmaceutically acceptable salts thereof; experiments prove that the compounds can be used for treating or preventing diseases related to protein kinase activity, such as leukemia and lymphoma, by inhibiti
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.
Synthesis and biological activity of thieno[3,2-d]pyrimidines as potent JAK3 inhibitors for the treatment of idiopathic pulmonary fibrosis
Zhu, Yanming,Zheng, Xu,Wang, Changyuan,Sun, Xiuli,Sun, Huijun,Ma, Tengyue,Li, Yanxia,Liu, Kexin,Chen, Lixue,Ma, Xiaodong
, (2019/12/28)
Idiopathic pulmonary fibrosis (IPF) is a serious and fatal lung disease, with a median survival of only 3–5 years from diagnosis. Janus kinase 3 (JAK3) has a well-established role in the pathogenesis of various autoimmune diseases, including rheumatoid arthritis (RA) and autoimmune-related pulmonary fibrosis. In this study, through the use of a conformationally-constrained design strategy, a series of thieno[3,2-d]pyrimidines were synthesized as potent JAK3 inhibitors for the treatment of IPF. Among them, the most potent JAK3 inhibitor, namely 8e (IC50 = 1.38 nM), significantly reduced the degree of airsacculitis and fibrosis according to hematoxylin-eosin (HE) staining assay for the lung tissue in the bleomycin (BLM)-induced pulmonary fibrosis mouse model. The clear reduction of the lung collagen deposition by the determination of Masson and hydroxyproline (HYP) content also demonstrated its efficacy in the treatment of fibrosis. In addition, 8e also reduced the expression of the inflammatory markers IL-6, IL-17A, TNF-α and malondialdehyde (MDA) in lung tissue, which indicated its higher anti-inflammatory activity compared with that of the reference agents (nintedanib and gefitinib). Furthermore, it possessed low cytotoxicity against normal human bronchial epithelia (HBE) cells (IC50 > 39.0 μM) and C57BL mice. All these evaluated biological properties suggest that 8e may be a potential JAK3 inhibitor for the treatment of IPF.
Azolo pyrimidine derivative, pharmaceutical composition thereof and application of azolopyrimidine derivative in tumor resistance
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Paragraph 0028-0032; 0066; 0079-0080, (2020/05/01)
The invention discloses an azolopyrimidine derivative, a pharmaceutical composition thereof and an application of the azolopyrimidine derivative in tumor resistance, and relates to the field of medicines and chemical engineering. The azolopyrimidine deriv
