5778-79-0Relevant articles and documents
Bistacrine derivatives as new potent antimalarials
Schmidt, Ines,Pradel, Gabriele,Sologub, Ludmilla,Golzmann, Alexandra,Ngwa, Che J.,Kucharski, Anna,Schirmeister, Tanja,Holzgrabe, Ulrike
, p. 3636 - 3642 (2016/07/20)
Linking two tacrine molecules results in a tremendous increase of activity against Plasmodia in comparison to the monomer. This finding prompted the synthesis of a library of monomeric and dimeric tacrine derivatives in order to derive structure–activity relationships. The most active compounds towards chloroquine sensitive Plasmodium strain 3D7 and chloroquine resistant strain Dd2 show IC50values in the nanomolar range of concentration, low cytotoxicity and target the cysteine protease falcipain-2, which is essential for parasite growth.
Synthesis of tacrine derivatives under solventless conditions
Khalilzadeh, Mohammad A.,Hosseini, Abolfazl,Tajbakhsh', Mahmoud
, p. 535 - 538 (2008/09/16)
(Chemical Equation Presented) Effects of microwave irradiation on the solid-phase synthesis of tacrine and its derivatives have been evaluated. Preparation of tacrine analogues under conventional conditions suffers from poor synthetic efficiency and usually gives low yield. Reaction of substituted anthranilonitrile with cyclohexanone under microwave irradiation gave a good to excellent yield of the corresponding substituted 9-amino-1,2,3,4- tetrahydroacridines.
SAR of 9-amino-1,2,3-4-tetrahydroacridine-based acetylcholinesterase inhibitors: Synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues
Recanatini, Maurizio,Cavalli, Andrea,Belluti, Federica,Piazzi, Lorna,Rampa, Angela,Bisi, Alessandra,Gobbi, Silvia,Valenti, Piero,Andrisano, Vincenza,Bartolini, Manuela,Cavrini, Vanni
, p. 2007 - 2018 (2007/10/03)
In this study, we attempted to derive a comprehensive SAR picture for the class of acetylcholinesterase (ACHE) inhibitors related to tacrine, a drug currently in use for the treatment of the Alzheimer's disease. To this aim, we synthesized and tested a series of 9-amino-1,2,3,4-tetrahydroacridine derivatives substituted in the positions 6 and 7 of the acridine nucleus and bearing selected groups on the 9-amino function. By means of the Hansch approach, QSAR equations were obtained, quantitatively accounting for both the detrimental steric effect of substituents in position 7 and the favorable electron-attracting effect exerted by substituents in positions 6 and 7 of the 9-amino-1,2,3,4-tetrahydroacridine derivatives. The three-dimensional (3D) properties of the inhibitors were taken into consideration by performing a CoMFA analysis on the series of AChE inhibitors made by 12 9-amino-1,2,3,4- tetrahydroacridines and 13 11H-indeno[1,2-b]quinolin-10-ylamines previously developed in our laboratory. The alignment of the molecules to be submitted to the CoMFA procedure was carried out by taking advantage of docking models calculated for the interactions of both the unsubstituted 9-amino-1,2,3,4- tetrahydroacridine and 11H-indeno[1,2-b]quinolin-10-ylamine with the target enzyme. A highly significant CoMFA model was obtained using the steric field alone, and the features of such a 3D QSAR model were compared with the classical QSAR equations previously calculated. The two models appeared consistent, the main aspects they had in common being (a) the individuation of the strongly negative contribution of the substituents in position 7 of tacrine and (b) a tentative assignment of the hydrophobic character to the favorable effect exerted by the substituents in position 6. Finally, a new previously unreported tacrine derivative designed on the basis of both the classical and the 3D QSAR equations was synthesized and kinetically evaluated, to test the predictive ability of the QSAR models. The 6-bromo-9- amino-1,2,3,4-tetrahydroacridine was predicted to have a pIC50 value of 7.31 by the classical QSAR model and 7.40 by the CoMFA model, while its experimental IC50 value was equal to 0.066 (±0.009) μM, corresponding to a pIC50 of 7.18, showing a reasonable agreement between predicted and observed AChE inhibition data.
