889948-89-4Relevant academic research and scientific papers
Development of Novel Dihydrofuro[3,4- d]pyrimidine Derivatives as HIV-1 NNRTIs to Overcome the Highly Resistant Mutant Strains F227L/V106A and K103N/Y181C
Kang, Dongwei,Sun, Yanying,Feng, Da,Gao, Shenghua,Wang, Zhao,Jing, Lanlan,Zhang, Tao,Jiang, Xiangyi,Lin, Hao,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
, p. 2458 - 2470 (2022/02/05)
Here, we report the design, synthesis, structure-activity relationship studies, antiviral activity, enzyme inhibition, and druggability evaluation of dihydrofuro[3,4-d]pyrimidine derivatives as a potent class of HIV-1 non-nucleoside reverse transcriptase
Identification of novel potent HIV-1 inhibitors by exploiting the tolerant regions of the NNRTIs binding pocket
Sun, Yanying,Kang, Dongwei,Da, Feng,Zhang, Tao,Li, Pei,Zhang, Baodan,De Clercq, Erik,Pannecouque, Christophe,Zhan, Peng,Liu, Xinyong
, (2021/02/16)
With our previously identified potent NNRTIs 25a and HBS-11c as leads, series of novel thiophene[3,2-d]pyrimidine and thiophene[2,3-d]pyrimidine derivatives were designed via molecular hybridization strategy. All the target compounds were evaluated for their anti-HIV-1 activity and cytotoxicity in MT-4 cells. Compounds 16a1 and 16b1 turned out to be the most potent inhibitors against WT and mutant HIV-1 strains (L100I, K103N, and E138K), with EC50 values ranging from 0.007 μM to 0.043 μM. Gratifyingly, 16b1 exhibited significantly reduced cytotoxicity (CC50 > 217.5 μM) and improved water solubility (S = 49.3 μg/mL at pH 7.0) compared to the lead 25a (S 50 = 2.30 μM). Moreover, molecular docking was also conducted to rationalize the structure-activity relationships of these novel derivatives and to understand their key interactions with the binding pocket.
COMPOUNDS FOR REGULATING FAK AND/OR SRC PATHWAYS
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, (2015/03/28)
The present application provides novel optionally substituted fused pyridine and pyrimidine bicyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating FAK and/or Src activity by administering a therapeutically effective amount of one or more of the compounds to a subject. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the FAK and/or Src pathway. Advantageously, these compounds perform as dual FAK and/or Src inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.
