847147-46-0Relevant academic research and scientific papers
2-(Arylpropionylamino)- and 2-(arylacryloylamino)benzophenones: Farnesyltransferase inhibition and antimalarial activity
Fucik,Kettler,Wiesner,Ortmann,Unterreitmeier,Krauss,Bracher,Jomaa,Schlitzer, Martin
, p. 744 - 752 (2007/10/03)
Structural variation of the 2-acylamino moiety of some benzophenone farnesyltransferase inhibitors led to the para-trifluoromethylphenylpropionyl derivative with relatively low farnesyltransferase inhibition but considerable antimalarial activity and no c
Non-thiol farnesyltransferase inhibitors: N-(4-acylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2-furyl]acrylic acid amides.
Kettler, Katja,Sakowski, Jacek,Silber, Katrin,Sattler, Isabel,Klebe, Gerhard,Schlitzer, Martin
, p. 1521 - 1530 (2007/10/03)
We have designed the nitrophenylfurylacryl-substituted benzophenone 4f as a non-thiol farnesyltransferase inhibitor utilizing a novel aryl binding site of farnesyltransferase. Variation of the 2-acylamino substituent at the benzophenone core structure of
Structure-activity relationships of novel anti-malarial agents. Part 4: N-(3-Benzoyl-4-tolylacetylaminophenyl)-3-(5-aryl-2-furyl)acrylic acid amides
Wiesner, Jochen,Mitsch, Andreas,Wissner, Pia,Kraemer, Oliver,Jomaa, Hassan,Schlitzer, Martin
, p. 2681 - 2683 (2007/10/03)
In a previous report, we have described novel anti-malarial compounds based on a 2,5-diaminobenzophenone scaffold. Here, we have invesigated acryloyl derivatives carrying a biaryl structure consisting of a terminal aryl residue and a central 2-furyl ring. Several compounds were obtained in the series of para-substituted phenylfurylacryloyl derivatives that displayed improved anti-malarial activity in comparison to earlier described derivatives. From the structure-activity relationships it can be deduced that there has to be a lipophilic moiety in the para-position of the terminal phenyl residue. Furthermore, there are indications that, alternatively, activity may benefit from the presence of a polar moiety with hydrogen bond acceptor properties.
Non-thiol farnesyltransferase inhibitors: Evaluation of different AA(X)-peptidomimetic substructures in combination with arylic cysteine replacements
Sakowski, Jacek,Boehm, Markus,Sattler, Isabel,Schlitzer, Martin
, p. 135 - 142 (2007/10/03)
In the course of our studies on non-thiol farnesyltransferase inhibitors based on the 2,5-diaminobenzophenone AAX-peptidomimetic substructure, we have developed the (4-nitrophenyl)butyryl (R1), the (2-naphthyl)acryloyl (R2), the 4-nitrocinnamoyl (R3), and the 5-(4-nitrophenyl)furylacryloyl (R4) groups as useful cysteine replacements. In this study, we combined these four groups with other AA(X)-peptidomimetic substructures (5-10: R = H) reported in the literature. The 5-(4-nitrophenyl)furylacryloyl moiety (R4) turned out to be the most useful non-thiol cysteine replacement yielding in all cases the most active inhibitors. By combination of this 5-(4-nitrophenyl)furylacryloyl moiety (R4) with the structurally simple AAX-peptidomimetics 4-aminobenzophenone (5) and 4-aminodiphenylsulfone (6) potent, readily accessible non-thiol farnesyltransferase inhibitors were obtained (IC50 = 12 nM and 10 nM).
