24484-96-6Relevant articles and documents
Design, synthesis and biological evaluation of novel substituted purine isosters as EGFR kinase inhibitors, with promising pharmacokinetic profile and in vivo efficacy
Gavriil, Efthymios-Spyridon,Doukatas, Aris,Karampelas, Theodoros,Myrianthopoulos, Vassilios,Dimitrakis, Spyridon,Mikros, Emmanuel,Marakos, Panagiotis,Tamvakopoulos, Constantin,Pouli, Nicole
, p. 393 - 409 (2019/05/22)
Novel substituted purine isosters, were designed and synthesized as potential inhibitors of the Epidermal Growth Factor Receptor (EGFR). The compounds were rationally designed through bioisosteric replacement of the central quinazoline core of lapatinib, an approved drug that inhibits both EGFR and HER2, another important member of this family of receptors. The new target molecules were evaluated as inhibitors of receptor phosphorylation at the cellular level, for their direct inhibitory action on the intracellular receptor kinase domain and for their cytotoxicity against the non-small cell lung cancer cell line A549 and breast cancer HCC1954, cell lines which are associated with overexpression of EGFR and HER2, respectively. The most potent derivatives were further studied for their cellular uptake levels and in vivo pharmacokinetic properties. One compound (23)displayed a noteworthy pharmacokinetic profile, and higher intracellular accumulation in comparison to lapatinib in the A549 cells, possibly due to its higher lipophilicity. This lead compound (23)was assessed for its efficacy in an EGFR positive xenograft model, where it successfully inhibited tumor growth, with a similar efficacy with that of lapatinib and with minimal phenotypic toxicity.
Discovery of nitropyridine derivatives as potent HIV-1 non-nucleoside reverse transcriptase inhibitors via a structure-based core refining approach
Wang, Jun,Zhan, Peng,Li, Zhenyu,Liu, Huiqing,De Clercq, Erik,Pannecouque, Christophe,Liu, Xinyong
, p. 531 - 538 (2014/05/06)
As a continuation of our efforts to discover and develop back-up analogs of DAPYs, novel substituted nitropyridine derivatives were designed via a structure-based core refining approach, synthesized and evaluated for their in vitro HIV-1 activity in MT-4 cells. Preliminary biological evaluation indicated that most of the compounds exhibited marked inhibitory activity against wild-type HIV-1 IIIB. Most notably, the compound 7b was identified as the most promising candidate in inhibiting HIV-1 replication with an EC 50 value of 0.056 μM and a selective index (SI) of 1251, which were much better than those of NVP (EC50 = 0.23 μM) and DLV (EC50 = 0.51 μM). Some other compounds, 7k, 7c, 7j and 7e, were also endowed with a favorable anti-HIV-1 potency (EC50 = 0.034, 0.11, 0.11 and 0.16 μM, respectively). Some antivirally active compounds also showed moderate inhibitory activity against RT. Preliminary structure-activity relationships (SARs) and molecular modeling of these new analogs provide valuable avenues for future molecular optimization.
IMIDAZOPYRIDINES AS INHIBITORS OF AURORA KINASE AND/OR FLT3
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Paragraph 00117; 00118, (2014/01/09)
The present invention relates to compounds of formula I: wherein R1 and R2 are as defined herein, or a pharmaceutically acceptable salt or solvate thereof. The compounds of formula I are inhibitors of aurora kinase and/or FLT3. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which aurora kinase and/or FLT3 activity is implicated.
