1374641-75-4Relevant academic research and scientific papers
Deuterated pyrimidine derivative with anti-cancer effect
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, (2020/07/21)
The invention relates to a deuterated pyrimidine derivative with an anti-cancer effect, and belongs to the field of medicines. The invention aims to solve the problems that the in-vivo half-life period of an anti-cancer drug WZ4002 is too short, the blood
Structural optimization of diphenylpyrimidine scaffold as potent and selective epidermal growth factor receptor inhibitors against L858R/T790M resistance mutation in nonsmall cell lung cancer
Yi, Yuanyuan,Wang, Luhong,Zhao, Dan,Huang, Shanshan,Wang, Changyuan,Liu, Zhihao,Sun, Huijun,Liu, Kexin,Ma, Xiaodong,Li, Yanxia
, p. 1988 - 1997 (2018/09/06)
A new class of thiodiphenylpyrimidine analogs (Thio-DPPY) were synthesized as potent and selective EGFR T790M inhibitors to overcome gefitinib resistance in nonsmall cell lung cancer (NSCLC). This structural optimization led to the identification of two p
Synthesis and biological evaluation of morpholine-substituted diphenylpyrimidine derivatives (Mor-DPPYs) as potent EGFR T790M inhibitors with improved activity toward the gefitinib-resistant non-small cell lung cancers (NSCLC)
Song, Zhendong,Huang, Shanshan,Yu, Haiqing,Jiang, Yu,Wang, Changyuan,Meng, Qiang,Shu, Xiaohong,Sun, Hunjun,Liu, Kexin,Li, Yanxia,Ma, Xiaodong
, p. 329 - 339 (2017/04/11)
Potential new EGFRT790M inhibitors comprised of structurally modified diphenylpyrimidine derivatives bearing a morpholine functionality (Mor-DPPYs) were used to improve the activity and selectivity of gefitinib-resistant non-small cell lung cancer (NSCLC) treatment. This led to the identification of inhibitor 10c, which displayed high activity against EGFRT790M/L858R kinase (IC50?=?0.71?nM) and repressed H1975?cell replication harboring EGFRT790M mutations at a concentration of 0.037?μM. Inhibitor 10c demonstrated high selectivity (SI?=?631.9) for T790M-containing EGFR mutants over wild type EGFR, suggesting that it will cause less side effects. Moreover, this compound also shows promising antitumor efficacy in a murine EGFRT790M/L858R-driven H1975 xenograft model without affecting body weight. This study provides new potential lead compounds for further development of anti-NSCLC drugs.
C-2 (E)-4-(Styryl)aniline substituted diphenylpyrimidine derivatives (Sty-DPPYs) as specific kinase inhibitors targeting clinical resistance related EGFRT790M mutant
Song, Anran,Zhang, Jianbin,Ge, Yang,Wang, Changyuan,Meng, Qiang,Tang, Zeyao,Peng, Jinyong,Liu, Kexin,Li, Yanxia,Ma, Xiaodong
, p. 2724 - 2729 (2017/04/17)
With the aim to overcome the drug resistance induced by the EGFR T790M mutation (EGFRT790M), herein, a family of diphenylpyrimidine derivatives (Sty-DPPYs) bearing a C-2 (E)-4-(styryl)aniline functionality were designed and synthesized as potential EGFRT790M inhibitors. Among them, the compound 10e displayed strong potency against the EGFRT790M enzyme, with the IC50 of 11.0?nM. Compound 10e also showed a higher SI value (SI?=?49.0) than rociletinib (SI?=?21.4), indicating its less side effect. In addition, compound 10e could effectively inhibit the proliferation of H1975 cells harboring the EGFRT790M mutation, within the concentration of 2.91?μM. Significantly, compound 10e has low toxicity against the normal HBE cell (IC50?=?22.48?μM). This work provided new insights into the discovery of potent and selective inhibitor against EGFRT790M over wild-type (EGFRWT).
Design and synthesis of sulfonamide-substituted diphenylpyrimidines (SFA-DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B-cell lymphoblastic leukemia
Liu, He,Qu, Menghua,Xu, Lina,Han, Xu,Wang, Changyuan,Shu, Xiaohong,Yao, Jihong,Liu, Kexin,Peng, Jinyong,Li, Yanxia,Ma, Xiaodong
, p. 60 - 69 (2017/04/24)
A new series of diphenylpyrimidine derivatives (SFA-DPPYs) were synthesized by introducing a functional sulfonamide into the C-2 aniline moiety of pyrimidine template, and then were biologically evaluated as potent Bruton's tyrosine kinase (BTK) inhibitors. Among these molecules, inhibitors 10c, 10i, 10j and 10k displayed high potency against the BTK enzyme, with IC50 values of 1.18?nM, 0.92?nM, 0.42?nM and 1.05?nM, respectively. In particular, compound 10c could remarkably inhibit the proliferation of the B lymphoma cell lines at concentrations of 6.49?μM (Ramos cells) and 13.2?μM (Raji cells), and was stronger than the novel agent spebrutinib. In addition, the inhibitory potency toward the normal PBMC cells showed that inhibitor 10c possesses low cell cytotoxicity. All these explorations indicated that molecule 10c could serve as a valuable inhibitor for B-cell lymphoblastic leukemia treatment.
Sulfamine pyrimidine compound, composition and purpose
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Paragraph 0079; 0080; 0093; 0094; 0095, (2017/07/23)
The invention relates to a sulfamine pyrimidine compound, a composition and a purpose. The sulfamine pyrimidine compound is concretely a compound shown by a general formula (I); each substituent group in the general formula (I) is defined as the descripti
HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Paragraph 0161; 0164;, (2015/10/05)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
Novel hybrids of (phenylsulfonyl)furoxan and anilinopyrimidine as potent and selective epidermal growth factor receptor inhibitors for intervention of non-small-cell lung cancer
Han, Chun,Huang, Zhangjian,Zheng, Chao,Wan, Ledong,Zhang, Lianwen,Peng, Sixun,Ding, Ke,Ji, Hongbin,Tian, Jide,Zhang, Yihua
, p. 4738 - 4748 (2013/07/19)
A series of hybrids (12a-k) from (phenylsulfonyl)furoxan and anilinopyrimidine were synthesized and biologically evaluated as epidermal growth factor receptor (EGFR) inhibitors for intervention of non-small-cell lung cancer (NSCLC). Compound 12k exhibited
MUTANT-SELECTIVE EGFR INHIBITORS AND USES THEREOF
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, (2012/05/31)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
