39217-08-8Relevant 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.
Design and synthesis of purine analogues as highly specific ligands for FcyB, a ubiquitous fungal nucleobase transporter
Lougiakis, Nikolaos,Gavriil, Efthymios-Spyridon,Kairis, Markelos,Sioupouli, Georgia,Lambrinidis, George,Benaki, Dimitra,Krypotou, Emilia,Mikros, Emmanuel,Marakos, Panagiotis,Pouli, Nicole,Diallinas, George
, p. 5941 - 5952 (2016/11/09)
In the course of our study on fungal purine transporters, a number of new 3-deazapurine analogues have been rationally designed, based on the interaction of purine substrates with the Aspergillus nidulans FcyB carrier, and synthesized following an effective synthetic procedure. Certain derivatives have been found to specifically inhibit FcyB-mediated [3H]-adenine uptake. Molecular simulations have been performed, suggesting that all active compounds interact with FcyB through the formation of hydrogen bonds with Asn163, while the insertion of hydrophobic fragments at position 9 and N6 of 3-deazaadenine enhanced the inhibition.
CYCLOPENTENOL NUCLEOSIDE COMPOUNDS, INTERMEDIATES FOR THEIR SYNTHESIS AND METHODS OF TREATING VIRAL INFECTIONS
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Page/Page column 87, (2008/06/13)
The present invention relates to compounds according to the structure (I), Where B is formula (Ia), formula (Ib) or formula (Ic); A is H, OR2 or halogen (F, Cl, Br, I, preferably F or Br, more preferably F); A' is H, OR2 or halogen (F, Cl, Br, I, preferably F or Br, more preferably F); A" is H or OR1, with the proviso that when A' is OR , A is H; and when A is OR2 , A' is H; X is C-R3 or N; Y is C-R3 or N; preferably X or Y is N and X and Y are not both simultaneously N; R3 is H or C1-C3 alkyl; D is H or NHR2; E is absent or H; G is O or NHR2; J is N or C-R4; K is N or C-H; R4 is H, halogen (F, Cl, Br, I), CN, -C(=O)NH2, NH2, NO2, -C=C-H (cis or trans) or -C≡C-H; Ra is H or CH3; Each R1 is independently H, an acyl group, a C1 - C20 alkyl or ether group, a phosphate, diphosphate, triphosphate, phosphodiester group; Each R2 is independently H, an acyl group, a C1 - C20 alkyl or ether group; and Pharmaceutically acceptable salts, solvates or polymorphs thereof.
