88138-72-1Relevant academic research and scientific papers
Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker
Abdelhameed, Ahmed,Feng, Mei,Joice, April C.,Zywot, Emilia M.,Jin, Yiru,La Rosa, Chris,Liao, Xiaoping,Meeds, Heidi L.,Kim, Yena,Li, Junan,McElroy, Craig A.,Wang, Michael Zhuo,Werbovetz, Karl A.
, p. 1901 - 1922 (2021/02/22)
Due to the limitations of existing medications, there is a critical need for new drugs to treat visceral leishmaniasis. Since arylimidamides and antifungal azoles both show oral activity in murine visceral leishmaniasis models, a molecular hybridization approach was employed where arylimidamide and azole groups were separated by phenoxyalkyl linkers in an attempt to capitalize on the favorable antileishmanial properties of both series. Among the target compounds synthesized, a greater antileishmanial potency against intracellular Leishmania donovani was observed as the linker length increased from two to eight carbons and when an imidazole ring was employed as the terminal group compared to a 1,2,4-triazole group. Compound 24c (N-(4-((8-(1H-imidazol-1-yl)octyl)oxy)-2-isopropoxyphenyl) picolinimidamide) displayed activity against L. donovani intracellular amastigotes with an IC50 value of 0.53 μM. When tested in a murine visceral leishmaniasis model, compound 24c at a dose of 75 mg/kg/day p.o. for five consecutive days resulted in a modest 33% decrease in liver parasitemia compared to the control group, indicating that further optimization of these molecules is needed. While potent hybrid compounds bearing an imidazole terminal group were also strong inhibitors of recombinant CYP51 from L. donovani, as assessed by a fluorescence-based assay, additional targets are likely to play an important role in the antileishmanial action of these compounds.
Synthesis and biological evaluation of azole-diphenylpyrimidine derivatives (AzDPPYs) as potent T790M mutant form of epidermal growth factor receptor inhibitors
Song, Zhendong,Jin, Yue,Ge, Yang,Wang, Changyuan,Zhang, Jianbin,Tang, Zeyao,Peng, Jinyong,Liu, Kexin,Li, Yanxia,Ma, Xiaodong
, p. 5505 - 5512 (2016/10/24)
A series of novel azole-diphenylpyrimidine derivatives (AzDPPYs) were synthesized and biologically evaluated as potent EGFRT790Minhibitors. Among these analogues, the most active inhibitor 6e not only displayed high activity against EGFRT790M/L858Rkinase (IC50?=?3.3?nM), but also was able to repress the replication of H1975 cells harboring EGFRT790Mmutation at a concentration of 0.118?μmol/L. In contrast to the lead compound rociletinib, 6e slightly reduces the key EGFRT790M-minduced drug resistance. Significantly, inhibitor 6e demonstrates high selectivity (SI?=?299.3) for T790M-containing EGFR mutants over wild type EGFR, hinting that it will cause less side effects.
Anilino-monoindolylmaleimides as potent and selective JAK3 inhibitors
McDonnell, Mark E.,Bian, Haiyan,Wrobel, Jay,Smith, Garry R.,Liang, Shuguang,Ma, Haiching,Reitz, Allen B.
, p. 1116 - 1121 (2014/03/21)
We designed a series of anilino-indoylmaleimides based on structural elements from literature JAK3 inhibitors 3 and 4, and our lead 5. These new compounds were tested as inhibitors of JAKs 1, 2 and 3 and TYK2 for therapeutic intervention in rheumatoid art
